NVXCoV 2373

At a glance

Originator Novavax
Developer Novavax; Serum Institute of India; Takeda
Class Adjuvants; COVID-19 vaccines; Protein vaccines; Synthetic vaccines; Viral vaccines
Mechanism of Action Immunostimulants

Orphan Drug Status

Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

No
New Molecular Entity No

Highest Development Phases

Marketed COVID 2019 infections

Most Recent Events

25 Mar 2024 Launched for COVID-2019 infections (In adolescents, In children) in Canada (IM)
25 Mar 2024 Launched for COVID-2019 infections (Prevention) in Canada (IM)
06 Mar 2024 Novavax plans a phase-II/III trial for COVID-2019 infections (NCT06291857)

Development Overview

Introduction

NVXCoV 2373 is a recombinant nanoparticle protein-based vaccine, being developed by Novavax, for prevention of COVID-2019 infections. The perfusion protein was developed using Novavax's proprietary recombinant protein nanoparticle technology platform, to generate antigens derived from the coronavirus spike (S) protein, including its proprietary patented saponin-based Matrix-M™ adjuvant to enhance immune responses and stimulate high levels of neutralising antibodies. NVXCoV 2373 contains purified protein antigen and cannot replicate, nor can it cause COVID-19. The vaccine has a favuorable product profile that allows handling in an unfrozen, liquid formulation which can be stored at 2°C to 8°C, allowing for distribution using standard vaccine channels. The product is launched in Austria, Germany, Poland, Sweden Canada, and Italy. The product is approved in the EU, Liechtenstein, Iceland and Norway for prevention of COVID-19 infections in individuals aged 12 and older. The product is now registered in South Korea for adolescents aged 12 through 17 years.The drug is registered in Japan, South Africa. The vaccine has emergency use authorisation, provisional registration or interim authorization in Australia, Taiwan, Indonesia, India, Philippines, New Zealand, Singapore, Bangladesh, Thailand, United Arab Emirates, South Korea for the prevention of COVID-2019 infections. It has also received conditional marketing authorisation (CMA) in Switzerland, the UK, Iceland, Liechtenstein, and Norway. The vaccine is now approved in the UK and Singapore for individuals aged 12 and older. The vaccine is approved to use as a booster for active immunization to prevent COVID-19 in adults aged 18 and older, in South Korea. Clinical development is ongoing in the US, Mexico and Puerto Rico.

As of October 2023, the Novavax COVID-19 vaccine, adjuvanted (original monovalent) is no longer authorized for use in the United States. Instead, the Novavax COVID-19 vaccine, adjuvanted (includes the spike protein from the SARS-CoV-2 omicron variant lineage XBB.1.5) (2023-2024 Formula) is registered in USA and is available at major retail pharmacies, physicians' offices, public health clinics and government entities across USA.

Matrix-M™ is a next-generation, patented saponin-based adjuvant, powered by a new formulation to provide a potent adjuvant effect. Saponins are steroid or triterpenoid glycosides, occurring in many plant species. In Matrix-M, purified saponin fractions are mixed with synthetic cholesterol and a phospholipid to form stable particles than can be readily formulated with a variety of vaccine antigens. Matrix-M™ stimulates the entry of antigen-presenting cells into the injection site and enhances antigen presentation in local lymph nodes thereby boosting the immune response. It induces both a cell-mediated and an antibody mediated immune response and also increases the opportunity for an immune reaction with longer duration, thereby reducing the number of vaccinations.

Company Agreements

In February 2024, Novavax and Gavi announced that they have successfully reached a settlement regarding the 2021 Advance Purchase Agreement (APA) for NVX-CoV2373. This milestone agreement marks the resolution of the pending arbitration associated with the APA, signifying a significant step forward in their collaboration.Novavax and Gavi agreed to terms to improve public health by boosting fair access to vaccines. Novavax paid $US 75 million upfront to Gavi and will pay $US 80 million yearly until 2028. Novavax's annual payment will be offset by an $US 80 million vaccine credit for qualifying sales in low-income countries. If demand rises, Novavax may offer an extra $US 225 million in vaccine credit over five years. In May 2021, Novavax and Gavi Vaccine Alliance entered in an advance purchase agreement for supply of NVX CoV 2373 to the COVAX Facility. According to the terms of the agreement, Novavax will manufacture and distribute $US 350 million doses of the vaccine to the countries participating under COVAX Facility.^[1]^[2]

In August 2023, Novavax updated the agreement and gave SK Bioscience the extension of exclusive commercial rights in South Korea until February 2029 and non-exclusive rights in Thailand and Vietnam until June 2028 and provides for a $4 million milestone to Novavax, as well as royalties on future product sales. In July 2022, Novavax and SK Bioscience expanded the manufacturing and supply agreement for a version of the Novavax COVID-19 vaccine (NVX-CoV2373) containing omicron variant and for the manufacture of the vaccine in prefilled syringes. The companies signed an agreement for the technology transfer of Novavax' proprietary COVID-19 variant antigen materials so that SK bioscience can manufacture the drug substance targeting COVID-19 variants including the Omicron BA.5 subvariant. Companies also have a collaboration and licensing agreement under which SK bioscience exclusively commercializes the Novavax COVID-19 vaccine in South Korea, and with Novavax, jointly commercializes the vaccine in Vietnam and Thailand. In May 2021, Novavax signed a non-binding memorandum of understanding (MoU) with the Ministry of Health and Welfare of Korea (MOHW) and SK bioscience to explore further cooperation in the development and manufacturing of vaccines, including NVX-CoV2373. In February 2021, Novavax and SK Bioscience expanded its collaboration and license agreement. In addition to the already existing manufacturing arrangement, SK Bioscience has obtained a license to manufacture and commercialize NVX CoV 2373, for sale to the Korean government. SK Bioscience will add significant production capacity under this new agreement. The agreement expands on an existing manufacturing arrangement between Novavax and SK Bioscience and calls for technology transfer related to the manufacturing of Novavax’ protein antigen, supply of Matrix M^TM adjuvant, and support to SK Bioscience as needed to secure regulatory approval. Concurrently, SK Bioscience has finalized an advance purchase agreement with the Korean government to supply 40 million doses of NVX CoV 2373 to the Republic of Korea beginning in 2021. Earlier, in August 2020, Novavax and SK bioscience entered into a development and supply agreement for the antigen component of NVX CoV2373, Novavax’ COVID-19 vaccine candidate, for supply to global markets including the COVAX Facility. In addition, the companies have signed a letter of intent with the Republic of Korea’s Ministry of Health and Welfare to work toward broad and equitable access to NVX CoV2373 for the global market as well as to make the vaccine available in South Korea. This contract development and manufacturing organisation agreement leverages a capacity reservation agreement between SK bioscience and the Coalition for Epidemic Preparedness Innovations (CEPI). Novavax' NVX CoV2373 will be manufactured using a part of the reserved capacity at SK Bioscience’s “L-House” facility.^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]

In March 2021, GlaxoSmithKline (now GSK) entered in a manufacturing agreement with Novavax and the UK Government's Department of Health to support upto 60 million doses of Novavax's NVX CoV 2373 for use in the UK. According to the terms of the agreement, beginning as early as May 2021, GlaxoSmithKline will provide fill and finish manufacturing capacity with a rapid technology transfer between the two companies. The fill and finish is the completion stage of vaccine which includes manufacturing, preparing vials of the final vaccine and packaging them for distribution and use^[11]^[12]

In February 2023, Novavax announced a modification to its existing agreement with the U.S. Department of Health and Human Services (HHS), in collaboration with the Department of Defense, to deliver up to 1.5 million doses of the NVX-CoV2373 in the US with initial delivery supplied in five-dose vials in the first quarter of 2023. Earlier, In July 2022, Novavax entered into supply agreement with US Department of Health and Human Services (HHS) and Department of Defense for the supply of Novavax' COVID-19 vaccine (NVX-CoV2373). Under this agreement, Novavax will supply an initial 3.2 million doses of COVID-19 vaccine once it receive U.S. Food and Drug Administration (FDA) Emergency Use Authorization (EUA) and a recommendation from the Centers for Disease Control and Prevention (CDC).^[13]^[14]

In June 2022, Novavax and Taiwan, participating under the COVAX facility, executed a supply agreement for NVX CoV2373^[15]

In January 2022, Novavax entered into purchase agreement with the Israel's Ministry of Health for the purchase of up to 5 million doses of NVX CoV2373 for prevention of COVID-2019 infections. Under the advance purchase agreement, Novavax will provide an initial 5 million doses of its protein-based vaccine with an option for Israel to purchase an additional 5 million doses. Novavax will work with the Ministry of Health to obtain the necessary authorizations and finalize plans for distribution in Israel pending regulatory approval.^[16]

In September 2021, Takeda Pharmaceutical entered into a supply agreement with the government of Japan Ministry of Health, Labour and Welfare to provide 150 million doses of Novavax’ vaccine candidate NVXCoV 2373 (TAK 019 in Japan) manufactured in Japan subject to licensing and approval. The details of the terms and conditions of the agreement are confidential. As part of a previously announced agreement with Novavax, Takeda is establishing the capability to manufacture NVXCoV 2373 at its facilities in Japan and aims to begin distribution in early calendar year 2022. Novavax is licensing and transferring manufacturing technologies to enable Takeda to manufacture the vaccine antigen and is supplying the Matrix-M^TM adjuvant to Takeda for fill/finish together with the antigen. Takeda is responsible for the Japanese clinical trial and regulatory submission to the pharmaceuticals and Medical Devices Agency (PMDA) and will distribute NVXCoV 2373 (TAK 019) in Japan should it be approved by the MHLW. Takeda’s efforts to transfer technology, establish production facilities and distribute Novavax’ vaccine candidate in Japan are supported by the MHLW under its supplementary budget for emergency maintenance associated with the vaccine production system
^[17]

In August 2021, Novavax entered into purchase agreement with the European Commission (EC) for the purchase of up to 200 million doses of NVX CoV2373 for prevention of COVID-2019 infections. The agreement covers the purchase of up to 100 million doses of the vaccine with the option for an additional 100 million doses through 2023.^[18]

In February 2021, Novavax and Takeda finalized the license agreement for NVX CoV 2373. In August 2020, Novavax entered into an agreement with Takeda for the development, manufacturing and commercialization of NVX CoV 2373 in Japan. Under the terms of the agreement, Novavax will license and transfer manufacturing technologies to enable Takeda to manufacture the vaccine antigen, and will supply the Matrix-M adjuvant to Takeda. Takeda will approximately produce 250 million doses of NVX CoV 2373 annually. Takeda will receive funding from the Government of Japan’s Ministry of Health, Labour and Welfare (MHLW), and will be responsible for regulatory submission, production and distribution of NVX CoV 2373 in Japan. Novavax will be eligible to receive development and commercial milestone payments, as well as a portion of the proceeds from revenues generated. Further financial details were not disclosed.^[19]^[20]^[21]

In March 2021, Mabion entered into manufacturing agreement with Novavax for the production of technical batches of antigen for NVX CoV 2373. Under the terms of the agreement, Mabion and Novavax will work together to transfer technology for the production of a technical batch of NVX CoV 2373, allowing for the assessment of manufacturing feasibility at a commercial scale. These initial steps for demonstration of feasibility will be conducted over the course of the first half of 2021. Upon successful completion, Mabion’s manufacturing facility could become a part of the supply chain for commercial production of Novavax' adjuvanted protein based vaccine candidate. Mabion will utilize its expertise in protein engineering, analytics and drug manufacturing at its state of-the-art facility, to optimize the production process and produce a full-scale technical batch. This batch, as well as other elements stipulated in the first stage of the contract, will be funded by non-refundable remuneration from Novavax^[22].^[22]

In February 2021, Novavax executed a binding Heads of Terms agreement with the government of Switzerland to supply six million doses of NVX CoV 2373 to the country. Novavax and government of Switzerland will negotiate a final agreement with initial delivery of vaccine doses slated to ship following successful clinical development and regulatory review.^[23]

In January 2021, Novavax finalised an advance purchase agreement with the Government of Canada to supply up to 76 million doses of NVX CoV 2373. The Government of Canada has committed to purchase 52 million doses of the vaccine with the option for up to an additional 24 million doses. The company expects to supply NVX CoV 2373 to Canada beginning as early as the second quarter of 2021, following authorisation by Canada’s regulatory agency. Financial details of the agreement were not disclosed.^[24]

In January 2021, Baxter BioPharma Solutions entered into an agreement to provide sterile manufacturing services for NVX CoV2373, Novavax’ COVID-19 recombinant nanoparticle vaccine candidate with Matrix-M™ adjuvant. Additional details of the agreement were not disclosed^[25]

In January 2021, Novavax executed its advance purchase agreement with the Commonwealth of Australia for 51 million doses of NVX CoV2373, following agreement announced in November 2020. Novavax will work with Australia’s regulatory agency, the Therapeutics Goods Administration (TGA), to obtain product approvals. The company aims to deliver initial doses by the mid of 2021. As part of the agreement, Australia will have the option to purchase up to an additional 10 million doses. Additional terms of the agreement were not disclosed.^[26]

In September 2020, Endo International's subsidiary Par Sterile Products entered into a non-exclusive agreement with Novavax to provide fill-finish manufacturing services for NVX CoV2373. Under the terms of the agreement, Par Sterile's Rochester facility initiated production of NVX CoV2373 final drug product, with initial batches to be used in Novavax' pivotal phase III clinical trial in the US. Par Sterile will also fill-finish NVX CoV2373 vaccine intended for commercial distribution in the US. Financial and other terms of the agreement were not disclosed.^[27]

In July 2020, Novavax and FUJIFILM Diosynth Biotechnologies entered into an agreement, under which latter will manufacture COVID 2019 vaccine, NVX CoV 2373 in bulk with expanded mass production, starting in early 2021. In August 2020, Novavax expanded its collaboration with FUJIFILM Diosynth Biotechnologies to manufacture the antigen component of NVX CoV2373 from its Billingham, Stockton-on-Tees site in the UK, in addition to its sites in North Carolina and Texas in the US.^[28]^[29]^[30]

In August 2020, Novavax signed a Heads of Terms (Term Sheet) with the Government of the United Kingdom (UK) for the purchase of 60 million doses of NVX CoV2373 vaccine, and a phase III clinical trial to assess the efficacy of the vaccine in the UK population. Under the terms of the agreement, Novavax will supply 60 million doses of NVX-CoV2373 to the UK beginning as early as the first quarter of 2021.^[29]

In September 2020, Novavax and Serum Institute of India amended its licensing agreement to manufacture the antigen component of NVX CoV2373, Novavax’ COVID-19 vaccine candidate. Under this ammended agreement, Novavax increases its manufacturing capacity of NVX CoV2373 to over two billion doses annually by 2021. Earlier, in August 2020, Novavax and Serum Institute of India entered a licensing agreement for the development and commercialization of NVX CoV2373. Under the terms of the agreement, Serum Institute gained exclusive rights to commercialize NVX CoV2373 in India and non-exclusive rights to commercialize in other low and middle income countries (LIMC). The companies will partner for clinical development, co-formulation, filling and finishing and commercialization of NVX CoV2373, while Serum Institute will be responsible for regulatory submissions and marketing authorizations. NovaVax will provide both vaccine antigen and Matrix-M adjuvant. The companies intend to share revenues. Further financial details of the agreement were not disclosed as of August 2020.^[31]

Novavax and AGC Biologics, in June 2020, entered into an agreement, under which the latter will manufacture Matrix-M™, the adjuvant component of NVX-CoV2372.^[32]

In April 2020, Emergent BioSolutions and Novavax expanded their manufacturing and supply agreement to manufacture seasonal influenza nanoparticle vaccine. As per the terms of agreement, Emergent will provide molecule-to-market contract development and manufacturing (CDMO) services to produce Nanovax seasonal influenza nanoparticle vaccine including large-scale production of the seasonal influenza nanoparticle vaccine. Emergent also will provide drug substance manufacturing services, including technology transfer and process validation and performance qualification to pave the way for commercial manufacturing. The agreement is an expansion of their original manufacturing and supply agreement signed in March 2020. Expanded collaboration now includes seasonal influenza nanoparticle vaccine and COVID-19 coronavirus vaccine candidate. Emergent will support Novavax’s goals to advance their influenza program while maintaining the option to allocate capacity for a potential scaled-up COVID-19 program. As per the original agreement, Emergent will provide contract development and manufacturing services, supplying Novavax with coronavirus vaccine product candidate for preclinical testing and utilisation in a phase I trial. Emergent’s rapid deployment capabilities and expertise are also expected to provide Novavax scalability and capacity to produce the vaccine product for future stockpiling.^[33]^[34]

Key Development Milestones

In March 2024, Novavax launched Nuvaxovid™ XBB.1.5 vaccine in Canada for active immunization to prevent COVID-2019 inections, caused by SARS-CoV-2, in individuals aged 12 and older^[35].

In December 2023, Novavax announced protein-based adjuvanted non-mRNA COVID-19 vaccine is available in Italy for the prevention of COVID-2019 infections in individuals aged 12 and older^[36].

In December 2023, Novavax announced protein-based non-mRNA COVID-19 vaccine is available in Sweden for the prevention of COVID-19 in individuals aged 30 and older ^[37]

In December 2023, Novavax announced protein-based non-mRNA COVID-19 vaccine is available in Germany for the prevention of COVID-19 in individuals aged 12 and older^[38].

In December 2023, Novavax launched Nuvaxovid™ XBB.1.5 Vaccine (Recombinant protein, Adjuvanted) (NVX CoV 2601) for active immunization to prevent COVID-2019 inections, caused by SARS-CoV-2, in individuals aged 12 and older in Austria and Poland^[39]^[39].

In December 2023, Novavax reported that the Health Canada has granted expanded authorization for Nuvaxovid™ XBB.1.5 Vaccine (Recombinant protein, Adjuvanted) (NVX CoV 2601) for active immunization to prevent COVID-2019 inections, caused by SARS-CoV-2, in individuals aged 12 and older. The expanded authorization was based on non-clinical data showing that the vaccine induced functional immune responses against XBB.1.5, XBB.1.16 and XBB.2.3 variants. Additional non-clinical data demonstrated that the vaccine induced neutralizing antibody responses to subvariants BA.2.86, EG.5.1, FL.1.5.1 and XBB.1.16.6 as well as CD4+ polyfunctional cellular (T-cell) responses against EG.5.1 and XBB.1.16.6. The company intends to launch the candidate in Canada, in individuals, aged 12 and older, in the coming days^[40].

In January 2024, Novavax announced that UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for Nuvaxovid XBB.1.5 variant dispersion for injection, COVID-19 Vaccine (recombinant, adjuvanted) (NVX-CoV2601) for active immunization to prevent COVID-19 in individuals aged 12 and older. The authorization was based on non-clinical data^[41]. In October 2023, Novavax announced that the UK MHRA has granted full marketing authorisation for its prototype COVID-19 vaccine NVXCoV 2373 (Nuvaxovid™)for individuals aged 12 and older for active immunisation to help prevent COVID-2019. The authorisation was based on two phase III trials, PREVENT-19 conducted in the US and Mexico and a phase III trial in the UK as well as a phase 2IIa/b trial in South Africa^[42].

In October 2023, Novavax announced that the updated Nuvaxovid™ XBB.1.5 dispersion for injection COVID-19 Vaccine (recombinant, adjuvanted) (NVX-CoV2601) has been recommended for approval for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals aged 12 and older in the European Union by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency. The European Commission will review the CHMP recommendation and is expected to make a final decision in the coming days^[43].

In October 2023, Singapore's Health Sciences Authority (HSA) has granted full approval for Novavax's prototype COVID-19 vaccine, NVXCoV 2373 for active immunization to prevent COVID-19 infections in individuals aged 12 and older. The Singapore Ministry of Health has included NVXCoV 2373 in the National Vaccination Programme as a protein-based non-mRNA option for COVID-19 prevention. The approval was based on data from the PREVENT-19 trial [See below]^[44].

In October 2023, the US Food and Drug Administration amended the emergency use authorization (EUA) of the Novavax COVID-19 Vaccine, adjuvanted for use in individuals 12 years of age and older to include the 2023-2024 formula. The Novavax COVID-19 vaccine, adjuvanted, a monovalent vaccine, has been updated to include the spike protein from the SARS-CoV-2 omicron variant lineage XBB.1.5 (2023-2024 formula). As part of today’s action, the Novavax COVID-19 Vaccine, adjuvanted (original monovalent) is no longer authorized for use in the United States. The FDA granted the emergency use authorization of the Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula)^[45].

As of October 2023, U.S. CDC and Advisory Committee Recommend Use of Authorized and Approved 2023-2024 Monovalent XBB COVID-19 Vaccines^[46]

In October 2023, European Commission has granted approval for NVX CoV2373 (Nuvaxovid™ : XBB.1.5 dispersion for injection COVID-19 Vaccine-recombinant, adjuvanted; NVX-CoV2601) for active immunization to prevent COVID-19 infections caused by SARS-CoV-2 in individuals aged 12 and older in EU, Liechtenstein, Iceland and Norway^[47]. The decision follows the positive opinion given by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) earlier in May 2023, recommending the full Marketing Authorization (MA) of NVX CoV2373 for use as a primary series in individuals aged 12 and older and as a booster in individuals aged 18 and older for the prevention of COVID-19^[48]

In January 2023, Novavax announced that partner SK bioscience has received expanded manufacturing and marketing approval from the Korean Ministry of Food and Drug Safety (KMFDS) for Nuvaxovid™ (NVX-CoV2373) for use as a booster for active immunization to prevent COVID-19 in adults aged 18 and older. This approval was based on data from Novavax' phase II trial conducted in the U.S. and Australia, from a separate phase II trial conducted in South Africa, and from the United Kingdom-sponsored COV-BOOST trial. Prior to the approval, in September 2022, the Korean Centers for Disease Control and Prevention set out recommendations that advised that Nuvaxovid could be used as a booster in adults aged 18 and older^[49]. Earlier in January 2022, South Korea's Ministry of Food and Drug Safety (MFDS) approved a Biologics License Application (BLA) from SK bioscience for NVXCoV 2373 (Nuvaxovid™) COVID-19 Vaccine (recombinant, adjuvanted) for active immunisation in individuals 18 years of age and older for the prevention of COVID-19 caused by SARS-CoV-2. The vaccine will be manufactured and marketed in South Korea by SK Bioscience ^[50]. In November 2021, Novavax had announced submission of a BLA for NVX CoV2373 to the MFDS of South Korea for the prevention of COVID-2019 infection^[51]. In April 2021, Novavax in collaboration with SK bioscience initiated the rolling submission process for NVX CoV2373 to the MFDS^[21]. In August 2022, Novavax announced that its partner SK bioscience received a Post Approval Change Application approval from the Korean Ministry of Food and Drug Safety (KMFDS) for Nuvaxovid™ (NVX-CoV2373) COVID-19 vaccine for active immunization to prevent COVID-19 infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adolescents aged 12 through 17. The approval was based on data from the ongoing paediatric expansion of the Phase III PREVENT-19 trial of 2,247 adolescents aged 12 through 17 years across 73 sites in the US to evaluate the safety, effectiveness (immunogenicity), and efficacy of Nuvaxovid^[52].

In December 2022, Health Canada approved supplemental New Drug Submission application (sNDS) for NVX CoV2373 (Nuvaxovid™) COVID-19 vaccine in adolescents aged 12 through 17. The sNDS was based on data from the ongoing pediatric expansion of the Phase III PREVENT-19 trial [see trials below] in the US. The drug was subsequently approved in Canada ^[53].

In June 2023, Novavax reported that it has executed amended Canada Advance Purchase Agreement (APA), outlining an updated delivery schedule for Nuvaxovid™ and negotiated up to $350 million in 2023 payments^[8].

In November 2023, Novavax announced that World Health Organization (WHO) granted Emergency Use Listing (EUL) for Nuvaxovid™ (NVXCoV 2373) for active immunization to prevent COVID-19 in individuals aged 12 and older. The EUL assists 194 WHO member states in assessing vaccines and to expedite regulatory approvals to import and administer the vaccine. The EUL approval was based on the data from non-clinical studies^[54]. In November 2022, Novavax announced that the World Health Organization (WHO) has issued an updated Emergency Use Listing (EUL) for Nuvaxovid™ (NVX-CoV2373) COVID-19 vaccine for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a primary series of two doses in adolescents aged 12 through 17^[55]. Earlier, in December 2021, the WHO granted EUL for NVX CoV2373, for active immunization of individuals 18 years of age and older for the prevention of coronavirus disease 2019 caused by SARS-CoV-2. The grant of EUL was based on the totality of preclinical, manufacturing and clinical trial data submitted for review, including two pivotal phase III trials [see trials below]^[56]. In November 2021, Novavax announced the completion of its rolling submission to the WHO, for emergency use listing (EUL) of NVXCoV 2373 for the prevention of COVID-2019 infections. The submission included clinical data obtained from PREVENT-19 trail (see below)^[57]. Earlier, in September 2021, Serum Institute of India (SII) and Novavax filed a regulatory submission to the World Health Organization (WHO) for emergency use listing (EUL) of NVXCoV 2373. The submission to WHO is based on the companies' previous regulatory submission to the Drugs Controller General of India (DCGI)^[58]. Novavax intends to submit additional supplemental filing for its vaccine for EUL with the WHO. Earlier in August 2021, Serum Institute of India (SII) and Novavax completed the submission of all modules required for emergency use authorisation of NVXCoV 2373 to the Drugs Controller General of India (DCGI) and regulatory agencies in India, Indonesia and the Philippines for the initiation of review of the vaccine, including preclinical, clinical, and chemistry, manufacturing and controls data. A good manufacturing practice joint site inspection of SII was successfully completed by DCGI in May 2021. The vaccination regimen calls for two 0.5 ml doses (5 microgram antigen and 50 microgram Matrix-M adjuvant) given intramuscularly 21 days apart^[59].

In September 2022, Novavax announced that the Taiwan Food and Drug Administration granted EUA for Nuvaxovid™ (NVX-CoV2373) COVID-19 vaccine in in adolescents aged 12 through 17. The EUA was based on data from the ongoing pediatric expansion of the Phase III PREVENT-19 trial^[60].

In December 2023, Novavax announced that the Taiwan Food and Drug Administration granted EUA for Nuvaxovid™ (NVX-CoV2373) COVID-19 vaccine in individuals aged 12 and older. The authorization was based on non-clinical data showing that NVX CoV2373 induced functional immune responses for XBB.1.5, XBB.1.16 and XBB.2.3 variants. Additional non-clinical data demonstrated that Novavax's vaccine induced neutralizing antibody responses to subvariants BA.2.86, EG.5.1, FL.1.5.1 and XBB.1.16.6 as well as CD4+ polyfunctional cellular (T-cell) responses against EG.5.1 and XBB.1.16.6. These data indicate Novavax's vaccine can stimulate both arms of the immune system and induce a broad response against circulating variants^[61]

In August 2023, Novavax reported that it has initiated rolling submission of U.S. Biologics License Application (BLA) for full approval of the vacccine, adjuvanted for adults and adolescents aged 12 through 18^[8]. In August 2022, the US FDA granted expanded emergency use authorization (EUA) for adjuvanted (NVX-CoV2373), as two-dose primary series for active immunization to prevent COVID-19 infections in adolescents aged 12 through 17. The FDA EUA decision was based on data from the ongoing pediatric expansion of the phase III PREVENT-19 trial ^[62]. In August 2022, Novavax submitted an application to the US FDA for Emergency Use Authorization (EUA) of its protein-based COVID-19 Vaccine, adjuvanted for active immunization to prevent COVID-19 caused by the SARS-CoV-2 as a homologous and heterologous booster in adults. This application for EUA is supported by data from phase-3 PREVENT-19 trial and phase-II COV-BOOST trial^[63]. The US Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) in July 2022, voted unanimously to recommend the use of the Novavax COVID-19 Vaccine, Adjuvanted as a two-dose primary series in individuals aged 18 and older. In July 2022, the US FDA issued an emergency use authorization (EUA) for the Novavax COVID-19 Vaccine, adjuvanted for the prevention of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older. The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of the medical product under Section 564(b)(1) of the Food Drug and Cosmetic Act unless the declaration is terminated or authorization revoked sooner^[63]^[64]^[65].

In August 2022, Novavax reported that Medsafe granted expanded provisional approval of NVX CoV2373 (Nuvaxovid™), for active immunization to prevent COVID-19 infection caused by SARS-CoV-2 in adolescents aged 12-17 years of age. The provisional approval was based on data from the PREVENT-19 trial (see below) ^[66]. Earlier, in February 2022, Medsafe granted provisional approval of NVX CoV2373, for active immunization to prevent COVID-19 infection caused by SARS-CoV-2 in individuals 18 years of age and older in New Zealand. The vaccine will be supplied to New Zealand under the brand name Nuvaxovid™. In November 2021, the company had completed the submission of an application for provisional approval to Medsafe in New Zealand. The application was supported by the data obtained from the PREVENT-19 trial (see below). The process of application submission was initiated in March 2021^[67]^[68]^[69].

In August 2022, Novavax reported that the Medicines and Healthcare products Regulatory Agency (MHRA) granted expanded conditional marketing authorization (CMA) for NVX-CoV2373 (Nuvaxovid™) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adolescents aged 12 through 17 in the United Kingdom. The approval was based on data from the PREVENT-19 trial (see below) ^[70]. Earlier, in June 2022, Novavax announced that The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recommended Nuvaxovid™ COVID-19 Vaccine (recombinant, adjuvanted) for expanded conditional marketing authorization (CMA) in the European Union (EU) for adolescents aged 12 through 17. The recommendation was based on results from the phase III PREVENT-19, a pivotal trial of 2,247 adolescents aged 12 through 17 years across 73 sites in the U.S., to evaluate the safety, effectiveness (immunogenicity), and efficacy of Novavax' COVID-19 vaccine^[71]. In March 2022, Novavax announced submission of its request to expand the conditional marketing authorization (CMA) of Nuvaxovid™^[72].

In August 2022, Novavax announced that its partner SK bioscience received a Post Approval Change Application approval from the Korean Ministry of Food and Drug Safety (KMFDS) for Nuvaxovid™ (NVX-CoV2373) COVID-19 vaccine for active immunization to prevent COVID-19 infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adolescents aged 12 through 17. The approval was based on data from the ongoing paediatric expansion of the Phase III PREVENT-19 trial of 2,247 adolescents aged 12 through 17 years across 73 sites in the US to evaluate the safety, effectiveness (immunogenicity), and efficacy of Nuvaxovid^[52]

In June 2022, Novavax announced that the Taiwan Food and Drug Administration granted EUA for Nuvaxovid™ (NVX CoV2373) COVID-19 vaccine in individuals aged 18 years and over. The EUA was based on the totality of preclinical, manufacturing and clinical trial data submitted for review. This included two pivotal phase III clinical trials: PREVENT-19 and a UK-based trial [see below]^[15].

In June 2022, Novavax announced that the Vaccines and Related Biological Products Advisory Committee (VRBPAC) of the US FDA recommended the EUA of NVX CoV2373 for the prevention of COVID-2019 infections in individuals aged 18 years and over. The recommendation was based on pivotal phase III PREVENT-19 clinical trial [see below]^[73]. In April 2022, Novavax announced that the US FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) will review NVXCoV 2373 application for the prevention of COVID-2019 infections on 7 June 2022^[74]. In January 2022, Novavax announced the submission of a request to US FDA for EUA for NVX CoV2373 for immunization of individuals 18 year of age and older against SARS-CoV-2. The request for EUA is based on the totality of pre-clinical, clinical and manufacturing-related (CMC) data provided to the agency, including results of two large pivotal clinical trials that demonstrated an overall efficacy of approximately 90 percent and a reassuring safety profile^[75].

In July 2022, the European Commission (EC) approved the expanded conditional marketing authorization (CMA) of NVXCoV 2373 in the European Union (EU) for adolescents aged 12 through 17. The approval followed the positive recommendation by the European Medicines Agency's Committee for Medicinal Products for Human Use in June 2022. The authorization was based on data from the pediatric expansion of phase III PREVENT-19 trial [see below]^[76]. In January 2022, Novavax announced that it recently received conditional marketing authorisation (CMA) for NVXCoV 2373 (Nuvaxovid™) in the European Union, Iceland, Liechtenstein, and Norway ^[50]. In December 2021, European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) had recommended granting a conditional marketing authorisation for NVX-CoV2373 to prevent COVID-19 in people from 18 years of age. During the assessment CHMP had the support of EMA’s safety committee, PRAC and the COVID-19 EMA pandemic task force (COVID-ETF). The EMA recommendation follows a positive CHMP opinion based on an expedited review of the totality of manufacturing, preclinical, and clinical trial data submitted by the company, with the conclusion that the vaccine meets the stringent criteria set by the EU for efficacy, safety and quality^[77]^[78]. In November 2021, Novavax completed completed the submission of all data and modules which are required to review a Marketing authorisation application (MAA) by the European Medicines Agency (EMA), for the prevention of COVID-2019 infections. The final step to completing the application in the EU will be an invitation from EMA to file for Conditional Marketing Authorisation. The submission contains data from the phase III PREVENT-19 trial [see below] and another phase III trial [see below]^[79]. In November 2021, the European Medicines Agency (EMA) announced that it had started evaluating an application for conditional marketing authorisation for NVX CoV2373^[80]. In parallel, EMA’s safety committee (PRAC) completed the preliminary assessment of the risk management plan (RMP) proposed by the company. Furthermore, EMA’s committee for medicines for children (PDCO) has issued its opinion on the company’s paediatric investigation plan (PIP)^[81]. In February 2022, Novavax announced the first doses of Nuvaxovid™ have begun shipping to European Union (EU) member states^[82].

In February 2022, Health Canada granted authorization for registration of NVXCoV 2373 to prevent COVID-2019 infections in patients 18 years of age and older. The submission contains data from the phase III PREVENT-19 trial [see below] and another phase III trial [see below]^[83]. Earlier, in November 2021, Novavax completed its rolling regulatory submission to Health Canada for regulatory approval of NVXCoV 2373 to prevent COVID-2019 infections^[79].

In July 2022, Novavax announced that Australia's Therapeutic Goods Administration (TGA) granted expanded approval for provisional registration of NVXCoV 2373, for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to adolescents aged 12 through 17. The provisional registration was based on data from the ongoing pediatric expansion of PREVENT-19 (see below) ^[84]. In January 2022, Novavax announced that Australia's Therapeutic Goods Administration (TGA) has granted approval for provisional registration of NVXCoV 2373, for active immunization to prevent COVID-2019 infections caused by SARS-CoV-2 in individuals 18 years of age and older. The vaccine will be supplied to Australia under the brand name Nuvaxovid™^[85]. In October 2021, Novavax in collaboration with Serum Institute of India, had completed the rolling submission to the TGA for provisional approval of NVX CoV 2373 for COVID-2019 infections. Novavax completed the submission of all modules required by the TGA for the regulatory evaluation of NVXCoV 2373. This includes preclinical, clinical, and CMC data^[86]. Earlier, in March 2021, Novavax had initiated the rolling submission process for regulatory approval to TGA in Australia for NVX CoV 2373 for COVID-2019 infections^[69]^[87].

In July 2022, Novavax received expanded manufacturing and marketing approval from the Japan Ministry of Health, Labour and Welfare (MHLW) for primary immunization to prevent coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adolescents aged 12 through 17. The expanded approval was based on data from the ongoing pediatric expansion of a pivotal phase III PREVENT-19 trial of adolescents aged 12 through 17 years in the US (see below)^[88]. In April 2022, Takeda received manufacturing and marketing approval from the Japan Ministry of Health, Labour and Welfare (MHLW) for Nuvaxovid^{® i}ntramuscular injection (Nuvaxovid) for primary and booster immunization in individuals aged 18 and older in Japan. Takeda intends to distribute the vaccine doses purchased by the Government of Japan at the soonest^[89]. The approval is based on Takeda’s submission of a New Drug Application (NDA) to the Ministry of Health, Labour and Welfare (MHLW) in December 2021. The submission is based on the data from phase I/II study and two pivotal phase III trials (see below). Additional safety and efficacy data were submitted to support booster immunization, including a phase II trial conducted by Novavax in South Africa evaluating a booster dose given six months after primary immunization. Takeda submitted all available chemistry, manufacturing and controls (CMC), non-clinical and clinical data in December 2021. Additional CMC data will be subsequently submitted to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) during the NDA review period^[90].

In February 2022, the company announced that the that the Medicines and Healthcare products Regulatory Agency (MHRA) granted conditional marketing authorisation (CMA) for Nuvaxovid™ COVID-19 Vaccine (recombinant, adjuvanted) for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older in Great Britain. The MHRA decision was based on the totality of preclinical, clinical, and chemistry, manufacturing and controls (CMC) data reviewed by the agency. This includes two pivotal ongoing phase III clinical trials: PREVENT-19 [see below] which enrolled approximately 30 000 participants in the US and Mexico^[91].

In March 2022, Novavax and Serum Institute of India Pvt. Ltd reported that the Drugs Controller General of India (DCGI) granted emergency use authorization (EUA) for NVX CoV2373 for adolescents aged 12 to <18 years in India^[92]

In February 2022, in partnership with Serum Institute of India Pvt. Ltd (SIIPL), the Directorate General of Drug Administration granted emergency use authorization (EUA) for NVX CoV2373 in Bangladesh, in individuals aged 18 years and older^[93].

In April 2022, Novavax and Serum Institute of India announced that the Thailand Food and Drug Administration (Thai FDA) granted emergency use authorization (EUA) to prevent coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 18 years of age and older. The Thai FDA decision was based on the totality of preclinical, manufacturing and clinical trial data submitted for review including two pivotal phase III clinical trials PREVENT-19 and trial conducted in the UK [see below]^[94].

As of May 2022, Novavax announced submission of its request to regulatory authorities of Great Britain, Australia,New Zealand and South Korea for approval of NVX CoV2373 in adolescents^[95] .

In September 2022, South African Health Products Regulatory Authority granted authorization for registration of NVXCoV 2373 to prevent COVID-2019 infections in patients 18 years of age and older^[96].

In January 2022, Novavax and Serum Institute of India announced the submission of regulatory application to the South African Health Products Regulatory Agency (SAHPRA) for emergency use authorization (EUA) of Novavax' recombinant nanoparticle protein-based COVID-19 vaccine candidate with Matrix-M™ adjuvant in South Africa. The submission was based on the data from two pivotal phase III clinical trials: PREVENT-19, and a trial with almost 15,000 participants in the UK. In December 2021, Novavax completed the submission of the final data package, including the complete chemistry, manufacturing and controls module, to fulfill the prerequisites for emergency use authorization (EUA) application request to the US FDA for NVXCoV 2373, the company's recombinant nanoparticle protein-based COVID-19 vaccine with Matrix-M™ adjuvant^[97]^[98].

In November 2021, the Philippine Food and Drug Administration (FDA) granted emergency use authorization (EUA) for recombinant nanoparticle protein-based COVID-19 vaccine (COVOVAX™)with Matrix-M™ adjuvant, for prevention of COVID-2019 infections in individuals 18 years of age and older^[99].

In December 2021, the Ministry of Health Prevention granted EUA for NVX CoV2373 in the United Arab Emirates (UAE) in individuals aged 18 years and older under the brand name Nuvaxovid™^[93].

In December 2021, Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organisation (WHO) published its recommendation for use of NVXCoV 2373 with Matrix-M™ adjuvant, for the prevention of COVID-2019 infections. Under the published guidance, WHO recommended a 2-dose primary vaccination series in persons aged 18 years and older to be administered 3-4 weeks apart, as well as administration of an additional dose of NVX CoV2373 to immunocompromised persons between one and three months after dose 2 of the primary series. WHO also recommended use of the vaccine for peoples with comorbidities, breastfeeding women, and person with human immunodeficiency virus (HIV) infections. The organization also allowed co-administration of an inactivated seasonal influenza vaccine and any dose of NVX CoV2373^[100].

In November 2021, Novavax and Serum Institute of India announced that the National Agency of Drug and Food Control of the Republic of Indonesia (Badan Peng was Obat dan Makanan, Badan POM) had granted emergency use authorization (EUA) for Novavax's recombinant nanoparticle protein-based COVID-19 vaccine (COVOVAX™)with Matrix-M™ adjuvant, or recombinant spike protein of SARS-CoV-2 virus 5 mcg to induce immunity against SARS-CoV-2 to prevent COVID-2019 infections in adults, aged 18 years old and above. The product will be manufactured in India and marketed in Indonesia by Serum Institute of India^[101].

In August 2022, Swissmedic expanded its temporary authorisation of NVXCoV 2373 (Nuvaxovid™) in Switzerland for active immunisation to prevent COVID-2019 infections in children and adolescents aged between 12 to 17 years. The authorisation is based on data from the ongoing paediatric expansion of the phase III PREVENT-19 trial (see below)^[102]. Earlier in April 2022, Swissmedic granted conditional marketing authorization (CMA) for Nuvaxovid™ for active immunisation to prevent COVID-2019 infections in individuals 18 years of age and older. Previously in February 2022, Novavax submitted the conditional marketing authorization application to Swissmedic, the Swiss Agency for Therapeutic Products to review NVX CoV2373 use in adults. Swissmedic's submission for the regulatory evaluation of NVX CoV2373 incorporated data from two pivotal Phase 3 clinical trials [including PREVENT-19 trial (see below)] that demonstrated the vaccine's efficacy and safety ^[103]^[104].

In February 2022, the Singapore Health Sciences Authority (HSA) has issued interim authorization for NVXCoV 2373 for active immunization to prevent COVID-19 caused by SARS-CoV-2 in adults^[105]. In November 2021, Novavax submitted a regulatory application with the Singapore Health Sciences Authority (HSA) for interim authorisation of NVXCoV 2373 under the Pandemic Special Access Route (PSAR), for the prevention of COVID-2019 infections in Singapore. The application was supported by two pivotal phase III trials including PREVENT-19 (see below)^[106].

In September 2022, the Israel Ministry of Health granted an import and use permit to NVX-CoV2373 (Nuvaxovid™) in individuals aged 12 and older for active immunization to prevent coronavirus disease 2019 (COVID-19), as a primary series and as a heterologous booster for those previously vaccinated with mRNA vaccines. The permit was based on the recommendation of the Israeli Advisory Committee on Epidemics^[107].

In September 2023, Health Canada announced that it has received a submission from Novavax for the COVID-19 vaccine targeting the Omicron XBB.1.5 subvariant for people 12 years and older^[108].

In October 2021, Novavax announced completion of its rolling regulatory submission to the UK's Medicines and Healthcare products Regulatory Agency (MHRA) for authorization of NVXCoV 2373. It has now completed the submission of all modules required by MHRA for the regulatory review of NVXCoV 2373, including preclinical, clinical, and chemistry, manufacturing and controls (CMC) data^[109]. Earlier, in February 2021, Novavax announced initiation of the rolling submission process for regulatory approval to Health Canada, the European Medicines Agency (EMA), the US FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA). The company intends the reviews to continue while the company completes its pivotal phase III trials in the US and UK [see below] and through initial authorisation for emergency use granted under country-specific regulations^[18]^[110]^[111].

In March 2021, Novavax submitted open investigational new drug (IND) application for NVX CoV 2373 with the US FDA^[69].

In February 2021, Novavax announced a Memorandum of Understanding (MOU) with Gavi the Vaccine Alliance to provide 1.1 billion cumulative doses of NVX CoV2373 for the COVAX Facility^[112].

In November 2020, the US FDA granted Fast Track designation to NVX CoV2373 for the prevention of COVID-2019 infections^[113].

In April 2021, Novavax announced initiation of crossover arms in its phase IIb trial in South Africa [see below] and pivotal phase III trial [see below] in the UK. The crossover will also be initiated in phase III PREVENT-19 study (see below)^[114].

In October 2022, study 307 (Lot Consistency) achieved its primary endpoint. In September 2022, Novavax completed a phase III trial which evaluated the immunogenicity and safety of 3 lots of NVX CoV2373 in adults (NCT05463068; 2019nCoV-307). The randomised, observer-blinded study initiated in July 2022, enrolled 911 volunteers in the US^[115]^[116].

In February 2022, Novavax announced that the phase III PREVENT-19 trial achieved its primary effectiveness endpoint in the paediatric expansion part and demonstrated 80% efficacy overall in the delta variant. Earlier, in June 2021, Novavax announced that the phase III study met its primary efficacy endpoint with an overall 90.4% efficacy and a 100% protection against moderate and severe disease. In December 2023, Novavax completed the phase III PREVENT-19 trial which was initiated earlier in January 2021, for prevention of COVID-2019 infections. Previously, in December 2020, pivotal phase III PREVENT-19 trial had initiated to evaluate efficacy, immunogenicity and safety of NVX CoV 2373 in prevention of COVID-2019 infections in healty adult volunteers(NCT04611802, 2019nCoV-301). The randomised, placebo-controlled, double-blind, parallel, multicenter trial enrolled 33,000 healthy volunteers in the US, Puerto Rico and Mexico. This phase III clinical trial is being conducted with support from the US Government through Operation Warp Speed. In February 2021, Novavax completed enrollment of 30 000 healthy volunteers in the US and Mexico. In May 2021, Novavax announced that it has initiated a paediatric expansion, in adolescents (12 to < 18 years), of its ongoing phase III trial for NVX CoV 2373. The additional arm of the ongoing PREVENT-19 trial will evaluate the efficacy, safety and immunogenicity of NVX CoV 2373 in up to 3,000 adolescents aged 12-17 in the US. In August 2021, the US Centers for Disease Control and Prevention (CDC) stated that patients in the PREVENT-19 phase III trial met the criteria to be considered fully vaccinated two weeks after they have completed the vaccine series. In April 2021, the company initiated crossover arms in this phase III PREVENT-19 study. In April 2022, Novavax announced that it has initiated administration of the first booster doses of NVX CoV 2373 in the paediatric expansion of the PREVENT-19 pivotal phase III clinical trial. The study will evaluate the safety and immunogenicity of a third dose of NVX CoV 2373 among 2247 trial participants aged 12 through 17^[117]^[118]^[114]^[119]^[120]^[121]^[122]^[123]^[26]^[124]^[125]^[126]^[127]. In May 2022, data from the trial was released by Novavax ^[95]^[73]. In July 2022, results from the trial were released by Novavax^[128]. In December 2022, results from the trial were released by Novavax^[53].

In January 2021, Novavax announced that the phase III study met its primary efficacy endpoint with 89.3% efficacy. In March 2022, Novavax completed its first phase III, pivotal study that evaluated the efficacy, safety and immunogenicity of NVX CoV 2373 with Matrix-M (2019nCoV302; EudraCT2020-004123-16; NCT04583995). The randomised, placebo-controlled trial was initiated in September 2020 and enrolled 15138 participants in the UK. The trial was conducted in partnership with the UK Government’s Vaccines Taskforce. The trial has two primary endpoints. The first primary endpoint is first occurrence of PCR-confirmed symptomatic COVID-19 with onset at least 7 days after the second study vaccination in volunteers who have not been previously infected with SARS-CoV-2. The second primary endpoint is first occurrence of PCR-confirmed symptomatic moderate or severe COVID-19 with onset at least 7 days after the second study vaccination in volunteers who have not been previously infected with SARS-CoV-2. An interim analysis will be performed when 67% of the desired number of these cases has been reached. The data from the trial are expected to support regulatory submissions for licensure in the UK, the EU and other countries. In October 2020, Novavax announced that 5 500 volunteers are enrolled to date in the trial in the UK. In January 2021, Novavax released efficacy and safety data from this study. In March 2021, Novavax reported results from the trial. In May 2021, additional results from the trial were disclosed. Novavax, St George's Hospital and the University of London, before June 2021 conducted a sub-study as a part of the phase III programme which evaluated the safety, immunogenicity, and efficacy profile of NVX CoV 2373 vaccine when co-administered with seasonal influenza vaccines; an adjuvanted, trivalent seasonal influenza vaccine (aTIV) [see AdisInsight drug profile 800013987] or a cell-based, quadrivalent seasonal influenza vaccine (QIVc) [see AdisInsight drug profile 800018219]. Approximately half the participants co-vaccinated with NVX CoV 2373 plus influenza vaccines (n=217) while the remainder participants (n=214) received placebo plus influenza vaccines. Results released in June 2021, showed that NVX CoV 2373 efficacy was preserved in presence of influenza vaccines compared with those vaccinated with NVX CoV 2373 alone and demonstrate the promising opportunity for concomitant vaccination. In April 2021, the company initiated crossover arms in this pivotal phase III trial. In June 2021, data were published in the New England Journal of Medicine. In February 2022, updated data were released by the company. In May 2022, data from the trial was released by Novavax^[95]^[129]^[114]^[130]^[131]^[21]^[132]^[133]^[134]^[69]^[131]^[135]^[122]^[136].

In July 2022, Novavax initiated phase II/III Hummingbird™ global trial to evaluate the safety and immunogenicity of 2 primary doses and a booster dose of NVXCoV 2373 given 21 days apart in pediatric participants (3 age cohorts; six to < twelve years, two to < six years, and six to < twenty four months of age). (NCT05468736; 2019nCoV-503). Each age cohort will be conducted in 2 parts starting with the oldest age cohort (6 to < 12 years of age). The randomised, age dde-escalating trial intends to enrol approximately 3600 children in the US^[137]^[138].

As of May 2021, Novavax announced completion of enrolment of 1 600 participants by Serum Institute in the initial cohort of a phase II/III trial in India. Earlier in March 2021, Novavax and Serum Institute of India initiated the phase II/III trial in India for COVID-2019 infections^[21].

In January 2022, Novavax in collaboration with Bill and Melinda Gates Foundation completed a phase IIA/B trial that evaluated the effectiveness and safety of a coronavirus disease 2019 (COVID-19) vaccine (NCT04533399; 2019nCoV-501). The randomised trial was initiated in August 2020 and enrolled 4422 participants in South Africa^[139].

In April 2021, University of Oxford's initiated a phase II Com-COV2 trial to determine the reactogenicity and immunogenicity of heterologous prime/boost COVID-19 vaccine schedules (OVG2021/01; EudraCT2021-001275-16; 27841311). The randomised homologous/heterologous-boost vaccine administration study intends to enrol approximately 1050 patients in the UK^[140].

In January 2021, Novavax announced that the study met its primary efficacy endpoint in HIV-negative as well as HIV-positive volunteers^[131]. In August 2020, Novavax announced the initiation of a phase IIb trial in collaboration with the Wits University (or University of the Witwatersrand), to evaluate the efficacy of NVX CoV 2373 vaccine in healthy volunteers and in patients with HIV infections. The study is supported by a grant from the Bill & Melinda Gates Foundation. In November 2020, the randomised, placebo-controlled trial completes enrollment of 4 422 healthy volunteers and 245 medically stable, HIV-positive participants in South Africa^[130]^[141]^[139]. In January 2021, Novavax released efficacy data from this study^[131]. In March 2021, Novavax reported results from the trial. Updated results were released by the company in May 2021^[142]^[134]. In April 2021, In April 2021, the company initiated crossover arms in this study^[114].

In June 2022, Novavax completed a two-part phase I/II trial which was designed to evaluate the immunogenicity and safety of NVX CoV 2373 in healthy participants (2019nCoV-101; NCT04368988). In September 2020, NVX CoV 2373 was being evaluated in phase II portion of the study in both the US and Australia. In August 2020, the first volunteers were enrolled in the phase II portion of the phase I/II trial. The phase II expands on the age range by including older adults 60-84 years of age as approximately 50% of the trial’s population. In August 2020, Novavax announced that it has completed the phase I part of phase I/II trial, which was earlier initiated in May 2020 (SARS-CoV-2 rS) nanoparticle vaccine with or without Matrix-M adjuvant in healthy volunteers. In part 1, at least one and up to two NVX CoV 2373 constructs were evaluated in up to two cohorts. The two-part, randomized, observer-blinded, parallel, placebo-controlled trial initiated in May 2022 enrolled 1419 healthy volunteers, including the elderly in Australia and the US. The trial was supported by funding from the Coalition for Epidemic Preparedness Innovations (CEPI). First patient in the phase I portion of trial was enrolled in May 2020. Results from the phase I portion of the trial showed that NVX CoV 2373 with the Matrix-M adjuvant was well-tolerated with a robust immunogenicity profile. The candidate elicited robust elicited robust antibody responses numerically superior than those observed in human convalescent sera. In August 2020, safety and immunogenicity data from the trial were released by Novavax. The data from phase I part of trial was submitted to the US FDA and an independent safety monitoring committee^[143]^[144]^[141]^[145]^[32]^[146]^[147]^[148]^[135]. In September 2020, the results from phase I part of phase I/II trial were published in New England Journal of Medicine (NEJM-2020)^[123]^[149]. In August 2021, adverse events and immunogenicity data from a phase II portion of phase I/II trial in COVID-2019 infections released by Novavax^[150].

In March 2022, Takeda completed a phase I/II trial which evaluate the safety and immunogenicity of NVX CoV 2373 by intramuscular injection in healthy Japanese volunteers (NCT04712110;TAK-019-1501). The randomised trial was initiated in February 2021, and completed enrolment of 200 volunteers in Japan in March 2021^[93]^[21]. Company intends to submit study results to Japan Pharmaceuticals and Medical Devices Agency (PMDA) as part of the NDA filing process^[151]^[152].

In January 2024, pharmacodynamics data from preclinical trial for NVXCoV 2373 was released by the company^[41]

In November 2023, pharmacodynamics data from preclinical trial for NVXCoV 2373 was released by the company^[54].

In October 2023, pharmacodynamics data from preclinical trial for NVXCoV 2373 was released by the company^[44].

In June 2021, Novavax released preclinical data that demonstrated strong immunogenicity and protection against both the Alpha (B.1.1.7) variant, which was originally identified in the UK, and the Beta (B.1.351) variant^[153].

In August 2020, results from preclinical studies were released by Novavax^[145].

In preclinical results, NVX CoV 2373 demonstrated high immunogenicity, stimulated high levels of neutralising antibodies and efficient binding with receptors targeted by the SARS‑CoV‑2 wild-type virus^[148]^[154].

Financing information

In April 2022, Takeda received funding for the technology transfer and research and development to manufacture NVX CoV 2373 at its Hikari facility through the MHLW and Japan Agency for Medical Research and Development^[89].

As at January 2021, Novavax had an ongoing partnership with the Government of Canada in the regulatory review and delivery of a safe, effective COVID-19 vaccine^[24]. Also, prior to January 2021, the Government of Canada has signed an agreement with Novavax to provide up to 76 million doses of NVX CoV 2373 to Canada^[111].

In September 2020, The Bill & Melinda Gates Foundation, via its Strategic Investment Fund, provided at-risk funding of a further $US150 million to Gavi, bringing the total funding provided through this collaboration to $US300 million. The funds will be utilised to support the Serum Institute of India to manufacture COVID-2019 vaccine candidates by AstraZeneca and Novavax, and for future procurement of vaccines for India and low-and middle-income countries via Gavi’s COVAX AMC^[155].

As of September 2020, Novavax has secured $US2 billion in funding for its global coronavirus vaccine program including up to $US388 million in funding from the Coalition for Epidemic Preparedness Innovations (CEPI) (see below)^[27].

Novavax in August 2020, reported that the Bill & Melinda Gates Foundation provided a grant of $US15 million for a phase IIb trial [see above] for prevention of COVID-2019 infections in South Africa^[141].

In July 2020, Novavax received funding of $US1.6 billion as part of Operation Warp Speed (OWS) programme of the Department of Health and Human Services (HHS). The proceeds will be used to fund the late stage clinical trials of NVX CoV 2373, including a pivotal phase III trial. The funding will also support plan to submit for licensure with US FDA. This funding is being given by Biomedical Advanced Research and Development Authority (BARDA) under Department of Defense agreement (identifier MCDC OTA agreement number W15QKN-16-9-1002). The OWS agreement was amended in December 2020, Novavax was granted a funding of $US1.6 billion and is entitled to receive maximum funding up to $US1.75 billion to support certain activities related to the development of NVX CoV 2373, and including the manufacture and delivery of 100 million doses of NVX CoV 2373 to the US government. The OWS agreement will fund the late-stage clinical studies necessary to determine the safety and efficacy of NVX CoV 2373, including PREVENT-19. Funding under the OWS Agreement will also support the company's plans to file submissions for EUA and licensure with the US FDA (Novavax FORM 10-K, March 2021)^[156]^[126]^[157]^[145]. JPEO-CBRND is also providing funding of up to $US45.7 million under a separate agreement^[63].

In June 2020, Novavax made an agreement to sell its Series A convertible preferred stock, also convertible into common stock, to RA Capital in a private placement, the closing of which is expected to generate gross proceeds of approximately $US200 million. The proceeds are slated to be instrumental in the continued development of NVX CoV 2373 and also for progressing seasonal influenza nanoparticle vaccine (NanoFlu) [see Adis Insight Drug profile 800045522] toward BLA filing^[158].

In June 2020, Novavax was awarded a contract by the US Department of Defense (DoD) for the manufacturing of NVX CoV 2373 COVID-19 vaccine. The funding of upto $US60 million provided by the Defense Health Program, will be used in for producing several components of the NVX CoV 2373 vaccine that will be manufactured in the US. The funding will also used for delivery of 10 million doses of the vaccine, and to advance NVX CoV 2373 into phase II/III trials^[159]^[160].

In May 2020, Novavax announced that the Coalition for Epidemic Preparedness Innovations (CEPI) will invest up to an additional $US384 million to advance clinical development of NVX CoV 2373 . Novavax will use the CEPI funds to advance the drug into clinical testing. Earlier, the CEPI awarded an initial funding of $US4.4 million to finance the company's COVID-19 vaccine development in March 2020. This extended collaboration brings CEPI's total investment in NVX CoV 2373 to $US388 million, and the funding will be used to progress vaccine through phase I/II development. The funds will be also used for the process development and manufacturing of up to 100 million vaccine doses by end of 2020^[161]^[148]^[34]^[162].

Patent Information

In March 2021, Novavax was granted an US patent number US 10 953 089 B1 (application number US 16 997 001) by the US Patent Office related to NVX CoV 2373. The patent is entitled, "Coronavirus vaccine formulations", and claims related to the coronavirus spike (S) proteins and nanoparticles comprising the same, which are suitable for use in vaccines. The nanoparticles present antigens from pathogens surrounded to and associated with a detergent core resulting in enhanced stability and good immunogenicity. Dosages, formulations, and methods for preparing the vaccines and nanoparticles were included. The company has a pending patent application PCT US 2021 015 220
(Novavax FORM 10-K, March 2021)^[156].

Drug Properties & Chemical Synopsis

Route of administration IM
Formulation Injection
Class Adjuvants, COVID-19 vaccines, Protein vaccines, Synthetic vaccines, Viral vaccines
Mechanism of Action Immunostimulants
WHO ATC code
J07B-X (Other viral vaccines)
EPhMRA code
J7E9 (All other viral vaccines)

Indication	Biomarker Function	Biomarker Name	Number of Trials
COVID 2019 infections	Eligibility Criteria	T-cell surface antigen CD4 seryl-tRNA synthetase	1 1
COVID 2019 infections	Outcome Measure	suppression of tumorigenicity 14 (colon carcinoma) serine racemase serine peptidase inhibitor, Kunitz type 1 sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase) ACE2 3 more biomarker names Show less	1 3 1 1 4
influenza virus infections	Outcome Measure	suppression of tumorigenicity 14 (colon carcinoma) serine peptidase inhibitor, Kunitz type 1 sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase) 1 more biomarker names Show less	1 1 1

Drug Name	Biomarker Name	Biomarker Function
NVXCoV 2373		ACE2	Outcome Measure
	sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase)	Outcome Measure
	serine peptidase inhibitor, Kunitz type 1	Outcome Measure
	serine racemase	Outcome Measure
	seryl-tRNA synthetase	Eligibility Criteria
	suppression of tumorigenicity 14 (colon carcinoma)	Outcome Measure
	T-cell surface antigen CD4	Eligibility Criteria

Indication	Phase 0	Phase I	Phase II	Phase III	Phase IV
Influenza virus infections	-	-	1	-	-
COVID-19 respiratory infection	-	-	-	1	-
COVID 2019 infections	-	1	13	16	7
Pneumococcal infections	-	-	-	-	1

Indication	Qualifier	Patient Segment	Phase	Countries	Route / Formulation	Developers	Event Date
COVID 2019 infections	adolescents aged 12 through 17	In adolescents, In children	Marketed	Canada	IM / Injection	Novavax	25 Mar 2024
COVID 2019 infections	individuals aged 12 and older	In adolescents, In adults, In the elderly, Prevention	Marketed	Austria, Germany, Poland	IM / Injection	Novavax	11 Dec 2023
COVID 2019 infections	-	In adults, In the elderly, Prevention	Marketed	Sweden	IM / Injection	Novavax	14 Dec 2023
COVID 2019 infections	individuals aged 12 and older	Prevention	Marketed	Canada	IM / Injection	Novavax	25 Mar 2024
COVID 2019 infections	individuals aged 12 years and older	In adolescents, In adults, In children, In the elderly, Prevention	Marketed	Italy	IM / Injection	Novavax	14 Dec 2023
COVID 2019 infections	provisional Registration Provisional approval interim authorization Emergency use authorisation in 18 years and older; for new formula Emergency Use Autorisation Emergency use authorisation in 18 years and older conditional marketing authorisation in healthy volunteers and patients with HIV infection	Prevention	Registered	Australia, New Zealand, Singapore, South Africa, South Korea, Switzerland, Taiwan, USA, United Arab Emirates, United Kingdom	IM / Injection	Novavax	13 Sep 2022
COVID 2019 infections	-	Prevention	Registered	Japan	IM / Injection	Takeda	18 Apr 2022
COVID 2019 infections	Emergency Use Authorisation	In adolescents, Prevention	Registered	India	IM / Injection	Novavax, Serum Institute of India	22 Mar 2022
COVID 2019 infections	expanded approval for provisional registration; adolescents aged 12 through 17 adolescents aged 12 through 17 expanded conditional marketing authorization expanded manufacturing and marketing approval in adolescents aged 12 through 17 expanded provisional approval extended interim authorization; aged between 12 to 17 adolescents aged 12 through 17; under Emergency Use Authorization	In adolescents, Prevention	Registered	Australia, European Union, Iceland, Japan, Liechtenstein, New Zealand, Norway, Singapore, South Korea, USA, United Kingdom	IM / Injection	Novavax	12 May 2023
COVID 2019 infections	Emergency Use Authorisation Emergency use authorisation	Prevention	Registered	Bangladesh, India, Indonesia, Philippines	IM / Injection	Novavax, Serum Institute of India	28 Feb 2022
COVID 2019 infections	-	In adults, In the elderly, Prevention	Registered	European Union, Iceland, Liechtenstein, Norway	IM / Injection	Novavax	12 Jan 2022
COVID 2019 infections	individuals aged 12 and older	In adolescents, In adults, In the elderly, Prevention	Registered	Singapore	IM / Injection	Novavax	18 Oct 2023
COVID 2019 infections	emergency use authorization	In adults, In the elderly, Prevention	Registered	Thailand	IM / Injection	Novavax, Serum Institute of India	08 Apr 2022
COVID 2019 infections	Emergency use authorization in patients aged 12 years and older	In adolescents, In adults, In children, Prevention	Registered	Taiwan	IM / Injection	Novavax	20 Dec 2023
COVID 2019 infections	Conditional authorisation; aged between 12 to 17	In adolescents, In children, Prevention	Registered	Switzerland	IM / Injection	Novavax	02 Sep 2022
COVID 2019 infections	-	In adolescents, In adults, In children, In the elderly, Prevention	Registered	United Kingdom	IM / Injection	Novavax	18 Oct 2023
COVID 2019 infections	-	In children, Prevention	Phase III	USA	IM / Injection	Novavax	27 Dec 2020
COVID 2019 infections	-	In adolescents, In adults, In children, Prevention	Phase III	Mexico, Puerto Rico	IM / Injection	Novavax	28 Dec 2020
COVID 2019 infections	6 Months to 11 Years	In children, In infants, Prevention	Phase II/III	USA	IM / Injection	Novavax	19 Jul 2022

Adverse drug reaction	Total safety reports	Serious reports	First reports
Cardiovascular disorders	3	3	-
Chemically induced disorders	1	1	-
Eye disorders	1	1	-
Genitourinary disorders	1	1	-
Immunological disorders	3	3	-
Neurological disorders	1	1	-
Pigmentation	1	-	-
Respiratory tract disorders	1	1	-
Skin and connective tissue diseases	2	1	-

Scientific Summary

Adverse Events

Phase III

Additional results from a sub-study (as a part of main phase III trial) showed largely absent or mild local and systemic reactogenicity in when NVX CoV 2372 was given alone. NVXCoV 2373 continued to show a reassuring safety profile, with adverse events that were balanced between vaccine and placebo groups. Reactogenicity events were more common when NVX CoV 2372 was co-administered with influenza vaccines than alone. The AEs included tenderness (70.1% vs 57.6%, respectively) or pain (39.7% vs 29.3%, respectively) at injection site, fatigue (27.7% vs 19.4%, respectively), and muscle pain (28.3% vs 21.4%, respectively). The most common adverse reactions observed during clinical studies (frequency category of very common =1/10) were headache, nausea or vomiting, myalgia, arthralgia, injection site tenderness/pain, fatigue, and malaise. Rates of unsolicited AEs, MAAEs, and SAEs were low and balanced between the two groups. In a main phase III study, NVX CoV 2372 was well-tolerated with a reassuring safety profile. NVX CoV 2372 showed low levels of severe, serious, and medically attended adverse events in both vaccine and placebo group^[97]^[132]^[133]^[69]^[131]^[136].

Updated data from phase III trial showed NVX CoV 2372 was well-tolerated in adolescents aged 12 through 17 for covid-2019 infections. The most common AEs were injection site tenderness (71%), injection site pain (67%), headache (63%), myalgia (57%), fatigue (54%), malaise (43%), nausea or vomiting (23%), arthralgia (19%), injection site swelling (19%), pyrexia (17%), and injection site redness (17%). Most were mild-to-moderate in severity and lasted less than two days. No new safety concerns were observed through the placebo-controlled portion of the pediatric expansion^[53].

Updated data from the phase III PREVENT-19 trial showed no increase in reactogenicity in younger (12 to <15 years old) adolescents compared to older (15 to <18 years old) adolescents. No safety signal was observed through the placebo-controlled portion of the trial. Earlier, data from a phase III PREVENT-19 trial for prevention of COVID-2019 infections showed that the vaccine was well-tolerated. Serious and severe adverse events were reported to be low in number and balanced between vaccine and placebo groups. No single adverse event term were reported by more than 1% of participants. In assessing reactogenicity 7 days after Dose 1 and Dose 2, injection site pain and tenderness, generally mild to moderate in severity, were reported to be the most common local symptoms, lasting less than 3 days. The most common adverse reactions observed during clinical studies (frequency category of very common =1/10) were headache, nausea or vomiting, myalgia, arthralgia, injection site tenderness/pain, fatigue, and malaise. Among participants 18 through 64 years of age, solicited adverse reactions (AR) following administration of any dose of the Novavax COVID-19 Vaccine, Adjuvanted were injection site pain/tenderness (82.2%), fatigue/malaise (62.0%), muscle pain (54.1%), headache (52.9%), joint pain (25.4%), nausea/vomiting (15.6%), injection site redness (7.0%), injection site swelling (6.3%), and fever (6.0%). In participants 65 years of age or over, solicited ARs following administration of any dose of the Novavax COVID-19 Vaccine, Adjuvanted were injection site pain/tenderness (63.4%), fatigue/malaise (39.2%), muscle pain (30.2%), headache (29.2%), joint pain (15.4%), nausea/vomiting (7.3%), injection site swelling (5.3%), injection site redness (4.8%), and fever (2.0%). Among participants 12 through 17 years of age, solicited ARs following administration of any dose of the vaccine were injection site pain/tenderness (75.0%), headache (56.9%), fatigue/malaise (57.9%), muscle pain (49.0%), nausea/vomiting (19.9%), joint pain (16.2%), fever (16.9%), injection site swelling (8.0%), and injection site redness (7.5%). Most were mild-to-moderate in severity and lasted less than two days. Local and systemic reactogenicity was generally lower than or similar to adults, after the first and second dose. ^[60]^[118]^[97]^[125]^[127]^[128].

Phase II:

In a phase IIb trial NVX CoV 2372 was well-tolerated, with low levels of severe, serious (SAEs) and medically attended adverse events at day 35, balanced between vaccine and placebo groups^[134]^[139].

Results from phase II part of phase I/II trial demonstrated that the administration of the booster dose was generally well-tolerated. Local and systemic reactogenicity increased between dose 1, dose 2 and dose 3, with 90% of symptoms rated as mild or moderate after the third dose^[150]. Results from the phase I portion of a phase I/II trial showed that that NVX CoV 2373 with the Matrix-M adjuvant was well-tolerated with a reassuring safety profile. The reactogenicity events were generally mild. Tenderness and pain were the most frequent local symptoms reported post Dose 1 and the systemic events were individually less frequent with headache, fatigue and myalgia being reported most commonly and greater reactogenicity was reported, following the second dose, although the majority of symptoms were reported as = Grade 1. The average duration of events was < 2 days. There were no severe/mild (Grade 3) unsolicited adverse events through 28 days after dose 2. Most of the adverse events were mild and deemed not related to vaccination. No serious adverse events (SAEs) were reported. One participant had mild fever that lasted 1 day^[149]^[145]^[147].

In a phase III study 307 (Lot Consistency) treatment with NVXCoV2373 was safe and consistent across lots, with no serious related treatment-emergent adverse events (AE)^[115]^[116].

Pharmacodynamics

Summary

In preclinical studies NVXCoV 2373 demonstrated that it induced CD4+ polyfunctional cellular (T-cell) responses against EG.5.1 and XBB.1.16.6. These data indicate NVXCoV 2373 can stimulate both arms of the immune system and may induce a broad response against currently circulating variants^[44].

In preclinical studies, NVX CoV 2373 demonstrated high immunogenicity and stimulated high levels of neutralising antibodies. After a single immunisation, high levels of spike protein-specific antibodies with ACE-2 human receptor binding domain blocking activity and SARS-CoV-2 wild-type virus neutralising antibodies were observed. The high microneutralisation titers seen after one dose, increased eight fold with a second dose. In cynomolgus macaques, NVX CoV 2373 induced immunisation. The vaccine induced sterile immunity that prevented viral replication in the upper and lower respiratory tracts, thus demonstrating potential to reduce COVID-19 transmission. No evidence of enhanced disease following challenge was reported^[145]^[154].

In preclinical studies, mice vaccinated with any of the four regimens displayed elevated antibody titers against both the original and Beta (B.1.351) spike. Heterologous or bivalent vaccination is highly immunogenic against the prototype spike compared to monovalent approaches, while immunisation with monovalent recombinant spike protein antigen (rS-B.1.351) or bivalent spike resulted in the highest anti-B.1.351 spike IgG titers among regimens tested. Additionally, mice immunizsd with rS-B.1.351 alone produced elevated neutralising antibody titers to the Alpha (B.1.1.7) and Beta (B.1.351) strains compared to titers upon immunisation with the prototype-directed strain. Titers were similar in the heterologous and bivalent vaccine groups. Antibodies produced after vaccination with rS-B.1.351 inhibited binding between human angiotensin converting enzyme-2 receptor (hACE2) and the variant spike or original spike to the same degree. Mice were protected when challenged with live Alpha (B.1.1.7) or Beta (B.1.351) variant strains of SARS-CoV-2, whether immunised with prototype vaccine or rS-B.1.351 alone, in combination, or as a heterologous prime boost^[153].

The results from the preclinical study demonstrated that NVXCoV 2373 induced functional immune responses against XBB.1.5, XBB.1.16 and XBB.2.3 variants. It also induced neutralizing antibody responses to subvariants BA.2.86, EG.5.1, FL.1.5.1 and XBB.1.16.6 as well as CD4+ polyfunctional cellular (T-cell) responses against EG.5.1 and XBB.1.16.6. These data indicate that NVXCoV 2373 can stimulate both arms of the immune system and may induce a broad response against currently circulating variants^[54].

Pharmacodynamics data from non-clinical studies of NVX-CoV2373 showed that COVID-19 vaccine induced functional immune responses for XBB.1.5, XBB.1.16 and XBB.2.3 variants. Additional non-clinical data demonstrated that Novavax’s vaccine induced neutralizing antibody responses to subvariants JN.1, BA.2.86, EG.5.1, FL.1.5.1 and XBB.1.16.6 as well as CD4+ polyfunctional cellular (T-cell) responses against EG.5.1 and XBB.1.16.6. These data indicate Novavax’s vaccine can stimulate both arms of the immune system and induce a broad response against circulating variants^[41]

Immunogenicity

Summary

Phase III

In the phase III PREVENT-19 trial, both adults aged 18 and older and adolescents aged 12 through 17 showed the prototype Novavax COVID-19 vaccine (NVX-CoV2373) achieved its pre-specified immunologic endpoint. A single homologous booster dose was given to select adult participants aged 18 and older, approximately eight or 11 months after their primary series. Following a booster dose, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (anti-S) Immunoglobulin G (IgG; a type of antibody) levels increased significantly relative to pre-boost levels, rising above the level correlated with 95% vaccine efficacy in a recent USG study. Neutralizing antibodies against the prototype strain also increased by 34- to 27-fold compared to pre-boost levels when boosted at eight or 11 months. Boosting also increased IgG and human angiotensin converting enzyme 2 (hACE2) receptor inhibition antibody levels against Omicron BA.1, BA.2, and BA.5 variants, with levels that are comparable to those observed in phase III efficacy studies. Additional results from a sub-study (as a part of main phase III trial) showed that co-administration of NVX CoV 2373 with Influenza vaccines resulted in no change to influenza vaccine immune response, while a modest reduction in antibody responses to the NVX CoV 2373 vaccine was observed. NVX CoV 2373 efficacy in the sub-study was 87.5% (95% CI: -0.2, 98.4) while efficacy in the main study was 89.8% (95% CI: 79.7, 95.5). A reduction in the number of symptomatic COVID-19 cases in people who received NVX CoV 2373 (10 cases out of 7,020 people) compared with people given placebo (96 out of 7,019 people). Although there was decrease in the immunogenicity with concomitant vaccination, anti-Spike antibody levels were more than 3-fold higher than levels found in convalescent serum in those who received both vaccines. Additional results from a phase III trial showed efficacy of 88.9% in adults over the age of 65 and efficacy of 90.9% in adults with high-risk medical comorbidities. Updated results showed an efficacy of 96.4% (95% CI: 73.8, 99.5) against the original virus strain and 86.3% (95% CI: 71.3, 93.5) against the B.1.1.7/501Y.V1 variant circulating in the UK. The primary efficacy endpoint demonstrated an overall vaccine efficacy of 89.7% (95% CI: 80.2, 94.6) (median of 55 days of surveillance). 106 cases were observed, with 10 in the vaccine group and 96 in the placebo group. NVX CoV2373 was effective against severe disease, five severecases were observed in the study, and all occurred in the placebo group. Four of the five severe cases were attributed to the B.1.1.7/501Y.V1 variant. Fourteen days after dose 1, vaccine efficacy was 83.4% (95% CI: 73.6, 89.5). A phase III study met its primary efficacy endpoint showing 89.3% (95% CI: 75.2 – 95.4) efficacy of NVX CoV 2373 in healthy volunteers. Out of 62 cases, COVID-2019 infections were observed in 56 and 6 patients of placebo and vaccine group respectively and 61 were mild or moderate, and 1 was severe (in placebo group). Efficacy of NVX CoV 2373 by strain in 56 patients was 95.6% against the original COVID-19 strain and 85.6% against the UK variant strain. Later, the extended analysis from the trial showed that a high level of efficacy for NVXCoV 2373, was maintained over a 6-month period of surveillance. Additionally, the analysis showed vaccine efficacy of 82.5% (95% CI: 75.0, 87.7) in protection against all COVID-19 infection – both symptomatic and asymptomatic – as measured by PCR+ or anti-N seroconversion. In the expanded data collection window, vaccine efficacy was evaluated over a 6-month period from November 10, 2020, through May 10, 2021 (median of 101 days of surveillance). Additionally, the trial demonstrated continued protection with an overall vaccine efficacy of 82.7% (95% CI: 73.3, 88.8). Vaccine efficacy against severe disease was 100% (95% CI: 17.9, 100) during the 6-month efficacy collection window, in line with the initial analysis^[115]^[129]^[132]^[133]^[21]^[134]^[131]^[136].

In the pediatric expansion of phase III PREVENT-19 trial, which evaluated boosting in adolescents aged 12 through 17, a single homologous booster dose was showed neutralizing titers as 2.7-fold higher than those seen with primary vaccination, and a significant boost was observed for antibody against Omicron BA.1, BA.2, and BA.5. Previously, updated data from the trial achieved effectiveness endpoint in the paediatric expansion part and demonstrated 80% efficacy overall in the delta variant. NVX CoV2373 demonstrated overall protective efficacy of 79.5% (95% CI: 46.8, 92.1) against COVID-19 infections. Vaccine efficacy against the delta variant was 82.0% (95% CI: 32.4, 95.2. Earlier the trial met its primary endpoint and demonstrated 100% protection against moderate and severe disease and 90.4% (95% CI: 82.9; 94.6) efficacy overall. The trial found an efficacy of 90.4% reduction in the number of symptomatic COVID-19 cases from seven days after the second dose in people who received NVXCoV 2373 (14 cases out of 17,312 people) compared with people given placebo (63 out of 8,140 people). The trial also met its key secondary endpoint and showed 100% effectiveness (95% CI: 80.8, 100) against those variants that are not considered VoC or VoI. Sequence data showed 35 (65%) were VoC, 9 (17%) were VoI, and 10 (19%) were other variants. Against VoC/VoI, an efficacy of 93.2% (95% CI: 83.9, 97.1) was observed. Thirty-eight of the VoC/VoI cases were observed to be in placebo group and 6 were in the vaccine group. In addition, showed success among "high-risk" populations and an efficacy of 91.0% (95% CI: 83.6, 95.0), with 62 COVID-19 cases in the placebo group and 13 COVID-19 cases in the vaccine group^[115]^[118]^[124]^[125]^[127].

Phase II

A phase IIb study met its primary efficacy endpoint with 49.4% (95% CI: 6.1-72.8) efficacy of NVX CoV 2373. In 94% of HIV-negative volunteers, 60% efficacy (95% CI: 19.9-80.1) was observed with 29 COVID-2019 infections cases in the placebo group and 15 in the vaccine group. In placebo group, one severe case was observed and all other cases were mild or moderate. A complete analysis of vaccine efficacy among 147 PCR-positive cases (51 cases in the vaccine group and 96 in the placebo group) demonstrated an overall efficacy of 48.6% against predominantly variant strains (95% CI: 28.4, 63.1). All five cases of severe disease observed in the trial occurred in the placebo group. Among HIV-negative participants, 55.4% efficacy was observed (95% CI: 35.9, 68.9). The complete analysis showed that vaccine-induced protection began 14 days after dose 1 (42.7% 95% CI: 25.0, 56.3), and increased efficacy was observed 7 days after dose 2, the primary endpoint for the study. The complete analysis of the trial also indicates a modest protective effect of prior exposure with the original COVID-19 strain. Among placebo recipients, at 90 days of follow-up, the illness rate was 80% in baseline seronegative participants and 5.9% in baseline seropositive participants^[142]^[134]^[131]^[139].

Results from phase II trial demonstrated that a single booster dose of NVX-CoV2373, given six months after an initial two-dose regimen, elicited a 4.6-fold increase in functional antibody titers. Additionally, functional ACE-2 binding inhibition antibodies cross-reactive with the Delta (B.1.617.2) variant were more than 6-fold higher than the primary vaccination series. Twenty-eight days following boosting, anti-spike IgG increased approximately 4.6-fold compared to the peak response seen after the second dose (Day 217 GMEU = 200,408 (95% CI: 159,796; 251,342)). This boosted value represents a 3.7 to 4.4-fold increase in anti-spike IgG values that were associated with protection in Novavax' PREVENT-19 and UK phase III clinical studies. Wild-type neutralization responses increased approximately 4.3-fold compared to the peak response seen after Dose 2 (IC50 neutralization titers = 6,231 (95% CI: 4,738; 8,195)). This boosted value represents a 4.6 to 5.5-fold increase over the neutralization response associated with protection in the PREVENT-19 and UK phase III clinical trials. Older participants (aged 60-84) showed a 5.4-fold increase in antibody responses, while younger participants (aged 18-59) showed a 3.7-fold increase. Very high levels of functional antibodies to the Alpha (B.1.1.7), Beta (B.1.351) and Delta variants were induced by boosting with NVX-CoV2373, with a 6.6-fold higher Delta variant-specific response when compared to the Delta response observed with the primary vaccination series^[150]. Results from the phase I portion of a phase I/II trial showed that that NVX CoV 2373 induced neutralization titers in all the volunteers. Both 5 µg and 25 µg adjuvanted doses generated peak geometric mean titer (GMT) greater than 1:3,300 (5 µg adjuvanted dose group peak GMT: 3,906 (95% CI: 2,556; 5,970). Post administration of a single dose of vaccine, all the volunteers developed anti-spike IgG antibodies, and many also developed wild-type virus neutralizing antibody responses. However after the second dose, all (100%) the volunteers developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID-19 disease. Also, the IgG antibody response was highly correlated with neutralization titers, demonstrating that a significant proportion of antibodies were functional. The adjuvant was dose-sparing, with the lower 5 µg dose of NVX-CoV2373 performing comparably with the 25 µg dose. In a subset of vounteers, and NVX CoV 2373 induced antigen-specific polyfunctional CD4⁺ T cell responses with a strong bias toward the Th1 phenotype (IFN-g, IL-2, and TNF-a)^[145]^[147].

Therapeutic Trials

Phase I/II:

Results from phase I portion of phase I/II trial showed that, administration of NVX CoV2373 in healthy volunteers resulted in eliciting effective immune responses against COVID-19 infections. The addition of adjuvant (Matrix-M™ ) helped in enhanced immune responses, was antigen dose–sparing and induced a T helper 1 (Th1) response. Adjuvanted regimens induced antigen-specific polyfunctional CD4+ and T-cell responses that were reflected in IFN-γ, IL-2, and TNF-α production on spike protein stimulation were observed. The two-dose 5-μg adjuvanted regimen induced geometric mean anti-spike IgG (63,160 ELISA units) and neutralization (3906) responses that exceeded geometric mean responses in convalescent serum from mostly symptomatic Covid-19 patients^[149].

Phase III: Results from phase III studies reported increased immune responses comparable to or exceeding levels associated with protection. Data indicated robust immune responses in adolescents, including increased IgG and receptor inhibition titers against a wide array of variants, including Omicron, following a 2-dose series. Responses in adolescents were 2- to 4-fold higher than adults against all evaluated variants^[163].

Results from PREVENT-19 phase III trial in adolescent demonstrated 80% overall clinical efficacy and 82% efficacy against Delta variant. Achieved primary effectiveness endpoint and demonstrated comparability to adult population^[95]. In the pivotal phase III PREVENT-19 trial, NVX CoV2373 demonstrated 90.4% efficacy (95% CI, 82.9-94.6; P < 0.001)^[73]^[127].

Results from phase III trial in UK demonstrated 82.5% efficacy in protection against all COVID-19 infection, as measured by PCR+ or anti-N seroconversion. 82.7% overall efficacy against disease.100% efficacy against severe disease^[95]

In a phase III study 307 (Lot Consistency) achieved its primary endpoint. It showed that three lots of the Novavax COVID-19 vaccine induced consistent immune responses in adults aged 18 to 49. Further, anti-S IgG titers were within the range previously found to correlate with high efficacy in the PREVENT-19 phase III trial^[115]^[116].

Organisation	Involvement	Countries
Novavax	Originator	USA
Novavax	Owner	USA
SK Bioscience	Market Licensee	South Korea, Thailand, Vietnam
Serum Institute of India	Licensee	India
Takeda	Licensee	Japan
Bill & Melinda Gates Foundation	Funder	USA
National Institute for Health Research	Funder	United-Kingdom
Department of defence	Funder	USA
Biocelect	Funder	Australia
Department of Health & Human Services	Funder	Australia
Japan Agency for Medical Research and Development	Funder	Japan
Gavi the Vaccine Alliance	Funder	Switzerland
Coalition for Epidemic Preparedness Innovations	Funder	Norway
National Institute for Health Research	Collaborator	United-Kingdom
UK Government's Department of Health	Collaborator	United Kingdom
The University of the Witwatersrand	Collaborator	South-Africa

Expected Date	Event Type	Description	Updated
30 Aug 2024	Trial Update	Novavax plans a phase-II/III trial for COVID-2019 infections (NCT06291857)	08 Mar 2024
31 Dec 2023	Regulatory Status	Novavax announces intention to submit application for approval of updated protein-based non-mRNA COVID-19 vaccine in the coming weeks ^[44]	25 Oct 2023
31 Dec 2022	Regulatory Status	Takeda intends to distribute NVX CoV 2373 in Japan in 2022 (9345263) (9316489) ^[89]	20 Apr 2022
31 Dec 2022	Regulatory Status	Novavax announces intention to submit regulatory filings for paediatric indication for COVID-2019 infections (In adolescents) globally in seond quarter of 2022 ^[95]	13 May 2022
30 Sep 2022	Trial Update	Novavax plans PREVENT-19 phase III expansion trial for COVID-2019 infections (In children, Prevention) in third quarter of 2022 ^[95]	11 Jun 2022
30 Jun 2022	Trial Update	Novavax plans additional trials for COVID-2019 infections in younger age groups globally during the second quarter of 2022 ^[118]	14 Feb 2022
30 Jun 2022	Trial Update	ANRS, Emerging Infectious Diseases plans a phase II trial for COVID-2019 infections (In adults, In elderly, Prevention) in Mali (IM) in June 2022 (NCT05409261)	14 Jun 2022
31 Mar 2022	Regulatory Status	Takeda expects approval of NVX CoV 2373 in Japan in FY2021 ^[165]	20 Apr 2022
31 Jan 2022	Regulatory Status	Novavax announces intention to submit emergency use authorization (EUA) application to US FDA following one month required by FDA EUA guidance ^[98]	02 Feb 2022
31 Dec 2021	Regulatory Status	Novavax plans filing for emergency use authorisation (EUA) of NVX CoV 2373 for COVID-2019 infections in the second quarter of 2021 ^[69]	09 Aug 2021
31 Dec 2021	Regulatory Status	Novavax plans to complete the rolling submission including complete CMC data package to the US FDA for COVID-2019 infections (Prevention) by the end of 2021 (9345263) ^[109]	04 Jan 2022
30 Nov 2021	Trial Update	Novavax plans a phase II trial for COVID-2019 infections (Prevention) in November 2021 (IM) (700344645) (NCT05112848)	29 Mar 2023
30 Sep 2021	Regulatory Status	Novavax announces intention to file for authorisation for COVID-2019 infections with the UK Medicines and Healthcare products Regulatory Agency (MHRA), in the third-quarter of 2021 ^[21]	29 Oct 2021
30 Sep 2021	Regulatory Status	Novavax plans to file for authorization with the US FDA and the European Medicines Agency (EMA), in the third quarter of 2021 ^[21]	08 Nov 2021
30 Sep 2021	Regulatory Status	Novavax plans to complete the rolling submission to the EMA for COVID-2019 infections (prevention) by third quarter of 2021 (9331603)	03 Nov 2021
31 Aug 2021	Regulatory Status	Novavax and Serum Institute of India announces intention to file for World Health Organisation Emergency Use Listing in August 2021 (9331864)	08 Nov 2021
30 Jun 2021	Regulatory Status	Novavax intends to receive authorisation from Canada’s regulatory agency by second quarter of 2021 ^[24]	24 Feb 2022
19 Apr 2021	Trial Update	University of Oxford plans a phase II Com-COV2 trial for COVID-2019 infections (Prevention) in United Kingdom in April 2021 (27841311) (700335925) (EudraCT2021-001275-16) ^[164]	21 Sep 2021
20 Feb 2021	Trial Update	Takeda plans a phase I/II trial for COVID-2019 infections (Prevention) (IM) (NCT04712110) (700332825)	25 Feb 2021
31 Dec 2020	Trial Update	Novavax plans a pivotal phase III trial for COVID-2019 infections (Prevention)in December 2020 in USA and Mexico (700324616) (9306446) (NCT04611802) (2019nCoV301) ^[130]	30 Dec 2020
30 Sep 2020	Trial Update	Novavax and UK government plans a phase III trial for COVID-2019 infections in UK in third quarter of 2020 (700326837) ^[29]	28 Sep 2020
31 May 2020	Trial Update	Novavax plans a phase I trial for COVID-2019-infections (Prevention) in Australia (IM) in May 2020 (NCT04368988) (700319239) ^[166]	17 May 2020

Event Date	Update Type	Comment
25 Mar 2024	Phase Change - Marketed	Launched for COVID-2019 infections (In adolescents, In children) in Canada (IM) ^[35] Updated 26 Mar 2024
25 Mar 2024	Phase Change - Marketed	Launched for COVID-2019 infections (Prevention) in Canada (IM) ^[35] Updated 26 Mar 2024
06 Mar 2024	Trial Update	Novavax plans a phase-II/III trial for COVID-2019 infections (NCT06291857) Updated 08 Mar 2024
24 Jan 2024	Regulatory Status	UK Medicines and Healthcare products Regulatory Agency (MHRA) granted marketing authorization for Nuvaxovid XBB.1.5 variant for active immunization to prevent COVID-19 in individuals aged 12 and older8 ^[41] Updated 31 Jan 2024
24 Jan 2024	Scientific Update	Pharmacodynamics data from a non-clinical studies in COVID-19 infections released by Novavax ^[41] Updated 31 Jan 2024
20 Dec 2023	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, In children, Prevention, In adults) in Taiwan (IM) ^[61] Updated 20 Dec 2023
18 Dec 2023	Phase Change - Preregistration	Preregistration for COVID-2019 infections (In adolescents, In adults, In children, Prevention) in Taiwan (IM) prior to December 2023 ^[61] Updated 20 Dec 2023
15 Dec 2023	Trial Update	Novavax completes the phase III clinical trials in COVID-2019 infections (Prevention) in Puerto Rico (IM), the USA (IM) and Mexico (IM) (NCT04611802) Updated 05 Jan 2024
14 Dec 2023	Phase Change - Marketed	Launched for COVID-2019 infections (In adults, In the elderly, Prevention) in Sweden (IM) ^[37] Updated 19 Dec 2023
14 Dec 2023	Phase Change - Marketed	Launched for COVID-2019 infections (In the elderly, Prevention, In adults, In adolescents, In children) in Italy (IM) ^[36] Updated 19 Dec 2023
11 Dec 2023	Phase Change - Marketed	Launched for COVID-2019 infections (In adolescents, In adults, In elderly, Prevention) in Austria (IM) ^[39] Updated 12 Dec 2023
11 Dec 2023	Phase Change - Marketed	Launched for COVID-2019 infections (In adolescents, In the elderly, Prevention, In adults) in Poland (IM) ^[39] Updated 12 Dec 2023
11 Dec 2023	Phase Change - Marketed	Launched for COVID-2019 infections (In adolescents, Prevention, In adults, In the elderly) in Germany (IM) ^[38] Updated 12 Dec 2023
05 Dec 2023	Regulatory Status	Health Canada grants expanded authorization to NVXCoV 2601 for COVID-2019 infections (In adults, In adolescents, In the elderly, Prevention) in Canada (IM) ^[40] Updated 07 Dec 2023
05 Dec 2023	Regulatory Status	Novavax announces intention to launch NVXCoV 2601 for COVID-2019 infections (Prevention, In adults, In the elderly, In adolescents) in Canada (IM) ^[40] Updated 07 Dec 2023
28 Nov 2023	Regulatory Status	World Health Organization (WHO) granted Emergency Use Listing (EUL) for NVXCoV 2373 ^[54] Updated 05 Dec 2023
28 Nov 2023	Scientific Update	Pharmacodynamics data from a preclinical trial in COVID-2019 infections released by Novavax ^[54] Updated 05 Dec 2023
31 Oct 2023	Regulatory Status	Novavax receives CHMP positive opinion for updated NVXCoV 2373 in COVID-19 infections (In adolescents, In adults, In the elderly, Prevention) ^[43] Updated 09 Nov 2023
31 Oct 2023	Regulatory Status	EMA approves NVX CoV2373 for COVID-19 infections (In adolescents, In adults, In the elderly, Prevention) in the EU, Liechtenstein, Iceland and Norway (IM) ^[47] Updated 02 Nov 2023
18 Oct 2023	Regulatory Status	Novavax announces intention to submit application for approval of updated protein-based non-mRNA COVID-19 vaccine in the coming weeks ^[44] Updated 25 Oct 2023
18 Oct 2023	Phase Change - Registered	Registered for COVID-2019 infections (In children, In adolescents, In adults, In the elderly, Prevention) in United Kingdom (IM) Updated 20 Oct 2023
18 Oct 2023	Phase Change - Registered	Registered for COVID-2019 infections (Prevention, In adolescents, In adults, In the elderly) in Singapore (IM) ^[44] Updated 20 Oct 2023
18 Oct 2023	Scientific Update	Pharmacodynamics data from a preclinical trial in COVID-2019 infections released by Novavax ^[44] Updated 20 Oct 2023
03 Oct 2023	Regulatory Status	The Novavax COVID-19 vaccine, adjuvanted (original monovalent) is no longer authorized for use in the United States ^[45] Updated 05 Oct 2023
03 Oct 2023	Regulatory Status	US FDA grants the emergency use authorization for Omicron XBB.1.5 subvariant COVID-2019 infections (for new formula) (In Adults, In adolescents, Prevention) ^[45] Updated 05 Oct 2023
12 Sep 2023	Regulatory Status	Novavax filed regulatory application with Health Canada for Omicron XBB.1.5 subvariant COVID-2019 infections (In Adults, In adolescents, Prevention) prior to September 2023 ^[108] Updated 14 Sep 2023
08 Aug 2023	Licensing Status	Novavax extends agreement with SK Bioscience for commercialization in South Korea, Vietnam and Thailand ^[8] Updated 14 Aug 2023
08 Aug 2023	Regulatory Status	Novavax initiates rolling submissions to US FDA for full approval of NVXCoV 2373 ^[8] Updated 14 Aug 2023
26 May 2023	Regulatory Status	Committee for Medicinal Products for Human Use (CHMP) adopts positive opinion of NVX CoV2373 for the prevention of COVID-19 ^[48] Updated 30 May 2023
12 May 2023	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, Prevention) in Singapore (IM) Updated 18 May 2023
29 Mar 2023	Trial Update	Novavax completes a phase III trial for COVID-2019 infections (prevention) in United Kingdom (NCT04583995) (EudraCT2020-004123-16) Updated 29 Mar 2023
05 Jan 2023	Regulatory Status	France’s Haute Autorite de Sante (HAS) recommends for use of NVXCoV 2373 as a two-dose primary vaccination series for COVID-19 infections (In adolescents, Prevention) in US . Updated 01 Feb 2023
07 Dec 2022	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, In children) in Canada (IM) ^[53] Updated 09 Dec 2022
07 Dec 2022	Scientific Update	Adverse events data from a phase III trial in Covid-2019 infections released by Novavax ^[53] Updated 09 Dec 2022
30 Nov 2022	Trial Update	Novavax completes a phase II trial for COVID-2019 infections (Prevention) in South Africa (NCT05112848) Updated 29 Mar 2023
29 Nov 2022	Regulatory Status	World Health Organization (WHO) issues update in Emergency Use Listing (EUL) for NVX CoV2373 in COVID-19 infections (In Adolescents) ^[55] Updated 01 Dec 2022
13 Oct 2022	Scientific Update	Efficacy and adverse events data from a phase III PREVENT-19 study 307 trial in COVID-19 infection released by Novavax ^[115] Updated 14 Oct 2022
16 Sep 2022	Regulatory Status	The Israel Ministry of Health grants NVX-CoV2373 an import and use permit for COVID-19 infections (Prevention, In adolescents, in adults, in elderly) in Israel (IM, Injection) ^[107] Updated 21 Sep 2022
16 Sep 2022	Regulatory Status	The Taiwan Food and Drug Administration (TFDA) recommends NVX-CoV2373 (Nuvaxovid™) COVID-19 Vaccine (Prevention, In adolescents) for expanded conditional marketing authorization (CMA) in Taiwan Updated 20 Sep 2022
16 Sep 2022	Scientific Update	Adverse event data from the phase III PREVENT-19 trial in COVID-2019 infections released by Novavax ^[60] Updated 20 Sep 2022
13 Sep 2022	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in South Africa (IM) ^[96] Updated 15 Sep 2022
02 Sep 2022	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, In children, Prevention) in Switzerland (IM) ^[102] Updated 06 Sep 2022
01 Sep 2022	Trial Update	Novavax completes a phase III trial in COVID-19 infection (Prevention) in USA (IM, Injection) (NCT05463068) Updated 19 Sep 2022
01 Sep 2022	Regulatory Status	The CHMP recommends NVX-CoV2373 (Nuvaxovid™) COVID-19 Vaccine (Prevention, In adults) for expanded conditional marketing authorization (CMA) in the European Union (EU) Updated 08 Sep 2022
26 Aug 2022	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, Prevention) in United Kingdom (IM) ^[70] Updated 30 Aug 2022
19 Aug 2022	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, Prevention) in USA (IM) ^[62] Updated 26 Aug 2022
18 Aug 2022	Phase Change - Preregistration	Preregistration for COVID-2019 infections (In adolescents, Prevention) in USA (IM) ^[62] Updated 26 Aug 2022
18 Aug 2022	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, Prevention) in New Zealand (IM) ^[66] Updated 22 Aug 2022
18 Aug 2022	Regulatory Status	New Zealand Medicines and Medical Devices Safety Authority (Medsafe) grants expanded provisional approval of NVXCoV 2373 for COVID-2019 infections (Prevention, In adoloscents) (IM) ^[66] Updated 22 Aug 2022
15 Aug 2022	Regulatory Status	Novavax submits application to US FDA for emergency use authorization for NVXCoV2373, adjuvanted as a booster ^[63] Updated 17 Aug 2022
11 Aug 2022	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, Prevention) in South Korea (IM) ^[52] Updated 17 Aug 2022
03 Aug 2022	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, Prevention) in Japan (IM) ^[88] Updated 03 Aug 2022
27 Jul 2022	Active Status Review	Novavax receives expanded manufacturing and marketing approval from the Japan Ministry of Health, Labour and Welfare (MHLW) for NVXCoV 2373 in COVID-2019 infections (Prevention, In adoloscents) (IM) ^[88] Updated 28 Jul 2022
26 Jul 2022	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, Prevention) in Australia (IM) ^[84] Updated 03 Aug 2022
25 Jul 2022	Regulatory Status	US Centers for Disease Control and Prevention recommends the use of NVXCo 2373 for COVID-19 infections in US ^[64] Updated 25 Jul 2022
19 Jul 2022	Phase Change - II/III	Phase-II/III clinical trials in COVID-2019 infections (Prevention, In children, In infants) in USA (IM) (NCT05468736) Updated 26 Jul 2022
13 Jul 2022	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in USA (IM) ^[65] Updated 15 Jul 2022
13 Jul 2022	Scientific Update	Adverse event data from the phase III PREVENT-19 trial in COVID-2019 infections released by Novavax ^[128] Updated 15 Jul 2022
11 Jul 2022	Trial Update	Novavax initiates a phase III trial in COVID-19 infection (Prevention) in USA (IM, Injection) (NCT05463068) Updated 19 Sep 2022
05 Jul 2022	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, Prevention) in Germany (IM) ^[38] Updated 12 Dec 2023
05 Jul 2022	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, Prevention) in European Union, Norway, Liechtenstein, Iceland (IM) ^[76] Updated 08 Jul 2022
23 Jun 2022	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in Taiwan (IM) ^[15] Updated 27 Jun 2022
23 Jun 2022	Regulatory Status	The CHMP recommends Nuvaxovid™ COVID-19 Vaccine (Prevention, In adolescents) for expanded conditional marketing authorization (CMA) in the European Union (EU) ^[71] Updated 27 Jun 2022
22 Jun 2022	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in Taiwan (IM) as of June 2022 ^[15] Updated 27 Jun 2022
08 Jun 2022	Trial Update	ANRS, Emerging Infectious Diseases plans a phase II trial for COVID-2019 infections (In adults, In elderly, Prevention) in Mali (IM) in June 2022 (NCT05409261) Updated 14 Jun 2022
07 Jun 2022	Regulatory Status	Vaccines and Related Biological Products Advisory Committee (VRBPAC) of the US FDA recommends approval of NVX CoV2373 for COVID-2019 infections in the US ^[73] Updated 09 Jun 2022
07 Jun 2022	Scientific Update	Efficacy data from the phase III PREVENT-19 trial in COVID-2019 infections released by Novavax ^[73] Updated 09 Jun 2022
01 Jun 2022	Trial Update	Novavax completes a phase I/II trial in COVID-2019 infections (Prevention) in Australia and the US (IM) (NCT04368988) Updated 29 Jul 2022
10 May 2022	Scientific Update	Efficacy data from the phase III trial in COVID-2019 infections released by Novavax ^[95] Updated 13 May 2022
10 May 2022	Scientific Update	Efficacy data from the phase III PREVENT-19 trial in COVID-2019 infections released by Novavax ^[95] Updated 13 May 2022
09 May 2022	Trial Update	Novavax plans PREVENT-19 phase III expansion trial for COVID-2019 infections (In children, Prevention) in third quarter of 2022 ^[95] Updated 11 Jun 2022
09 May 2022	Phase Change - Preregistration	Preregistration for COVID-2019 infections (In adolescents, Prevention) in New Zealand, South Korea, Australia, United Kingdom, European Union (IM) Updated 13 May 2022
09 May 2022	Regulatory Status	Novavax announces intention to submit regulatory filings for paediatric indication for COVID-2019 infections (In adolescents) globally in seond quarter of 2022 ^[95] Updated 13 May 2022
29 Apr 2022	Regulatory Status	US FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) will review NVXCoV 2373 application for the prevention of COVID-2019 infections on 7 June 2022 ^[74] Updated 05 May 2022
18 Apr 2022	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in Japan (IM) ^[89] Updated 20 Apr 2022
18 Apr 2022	Regulatory Status	Takeda intends to distribute NVX CoV 2373 in Japan in 2022 ^[90] ^[152] ^[89] Updated 20 Apr 2022
13 Apr 2022	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in Switzerland (IM) ^[103] Updated 15 Apr 2022
08 Apr 2022	Phase Change - Registered	Registered for COVID-2019 infections (Prevention, In adults, In the elderly) in Thailand (IM) ^[94] Updated 12 Apr 2022
31 Mar 2022	Regulatory Status	Novovax submits request to expand conditional marketing authorisation of NVXCoV 2373 (Adjuvant therapy, In adolescents) in the EU ^[72] Updated 04 Apr 2022
29 Mar 2022	Trial Update	Takeda completes a phase I/II trial for COVID-2019 infections in Japan (NCT04712110) Updated 29 Apr 2022
22 Mar 2022	Phase Change - Registered	Registered for COVID-2019 infections (In adolescents, In children, Prevention) in India (IM) ^[92] Updated 24 Mar 2022
28 Feb 2022	Trial Update	Novavax initiates a phase II trial for COVID-2019 infections (Prevention) in South Africa (NCT05112848) Updated 29 Mar 2023
28 Feb 2022	Phase Change - Registered	Registered (Emergency Use Authorisation) for COVID-2019 infections (Prevention) in Bangladesh (IM) ^[93] Updated 17 Mar 2022
28 Feb 2022	Scientific Update	Updated immunogenicity data from a phase III trial in COVID-2019 infections released by Novavax ^[129] Updated 02 Mar 2022
17 Feb 2022	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in Canada (IM) ^[83] Updated 24 Feb 2022
16 Feb 2022	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in Singapore (IM) ^[105] Updated 16 Feb 2022
14 Feb 2022	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in Switzerland (IM) ^[104] Updated 21 Feb 2022
10 Feb 2022	Scientific Update	Efficacy and adverse events data from the phase III PREVENT-19 trial in COVID-2019 infections released by Novavax ^[118] Updated 14 Feb 2022
10 Feb 2022	Trial Update	Novavax plans additional trials for COVID-2019 infections in younger age groups globally during the second quarter of 2022 ^[118] Updated 14 Feb 2022
03 Feb 2022	Phase Change	Provisional approval- Registered for COVID-2019 infections (Prevention) in New Zealand (IM) ^[67] Updated 08 Feb 2022
03 Feb 2022	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in United Kingdom (IM) ^[91] Updated 04 Feb 2022
02 Feb 2022	Regulatory Status	Novavax submits request for Emergency Use Authorization (EUA) to US Food and Drug Administration (FDA) for COVID-2019 Infections ^[75] Updated 02 Feb 2022
19 Jan 2022	Trial Update	Novavax completes a phase II trial in COVID-2019 infections (Prevention) in South Africa (IM) (NCT04533399) Updated 04 Mar 2022
19 Jan 2022	Phase Change	Provisional Registration - Registered for COVID-2019 infections (Prevention) in Australia (IM) ^[85] Updated 21 Jan 2022
12 Jan 2022	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in Norway, Liechtenstein, Iceland, European Union, South Korea (IM) ^[50] Updated 16 Jan 2022
10 Jan 2022	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in South Africa (IM) ^[97] Updated 13 Jan 2022
31 Dec 2021	Phase Change - Registered	Registered (Emergency Use Authorisation) for COVID-2019 infections (Prevention) in United Arab Emirates (IM) ^[93] Updated 17 Mar 2022
31 Dec 2021	Regulatory Status	Novavax announces intention to submit emergency use authorization (EUA) application to US FDA following one month required by FDA EUA guidance ^[98] Updated 02 Feb 2022
22 Dec 2021	Scientific Update	Efficacy data from a phase III trial in COVID-2019 infections released by Novavax ^[163] Updated 28 Dec 2021
21 Dec 2021	Regulatory Status	World Health Organization (WHO) granted Emergency Use Listing (EUL) for NVX CoV2373 ^[100] ^[128] Updated 15 Jul 2022
21 Dec 2021	Regulatory Status	Strategic Advisory Group of Experts on Immunisation of World Health Organisation publish recommendation for use of NVXCoV 2373 for COVID-2019 infections (Prevention) ^[100] Updated 29 Dec 2021
20 Dec 2021	Regulatory Status	European Medicines Agency Committee for Medicinal Products for Human Use recommends granting conditional marketing authorisation to NVXCoV 2373 for COVID-2019 infections (Prevention) ^[78] Updated 23 Dec 2021
20 Dec 2021	Regulatory Status	Novavax intends to launch NVXCoV 2373 for COVID-2019 infections (Prevention) in European Union ^[77] Updated 23 Dec 2021
20 Dec 2021	Regulatory Status	Novavax receives CHMP positive opinion for conditional marketing authorisation to NVXCoV 2373 for COVID-2019 infections (Prevention) based on expediated review before December 2021 ^[77] Updated 23 Dec 2021
17 Dec 2021	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in India (IM) - Emergency Use Authorisation ^[56] Updated 23 Dec 2021
15 Dec 2021	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in Japan (IM) in December 2021 ^[90] Updated 17 Dec 2021
15 Dec 2021	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in United Arab Emirates (IM) before December 2021 ^[90] Updated 17 Dec 2021
24 Nov 2021	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in Singapore (IM) ^[106] Updated 26 Nov 2021
17 Nov 2021	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in Philippines (IM) ^[99] Updated 19 Nov 2021
17 Nov 2021	Regulatory Status	EMA’s committee for medicines for children (PDCO) issues its opinion on paediatric investigation plan (PIP) for NVXCoV 2373 in COVID-2019 infections (Prevention) ^[81] Updated 19 Nov 2021
17 Nov 2021	Regulatory Status	The European Medicines Agency (EMA) starts evaluating an application for conditional marketing authorisation for NVX CoV2373 in COVID-2019 infections (Prevention) ^[81] ^[80] Updated 19 Nov 2021
16 Nov 2021	Regulatory Status	Novavax submits paediatric investigation plan (PIP) for NVXCoV 2373 in COVID-2019 infections (Prevention) to the EMA in European Union before November 2021 ^[81] Updated 19 Nov 2021
15 Nov 2021	Trial Update	Novavax plans a phase II trial for COVID-2019 infections (Prevention) in November 2021 (IM) (NCT05112848) Updated 29 Mar 2023
15 Nov 2021	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in South Korea (IM) ^[21] ^[51] Updated 17 May 2021
09 Nov 2021	Biomarker Update	Biomarkers information updated Updated 11 Nov 2021
01 Nov 2021	Phase Change - Registered	Registered for COVID-2019 infections (Prevention) in Indonesia (IM) - Emergency Use Authorization ^[101] Updated 08 Nov 2021
01 Nov 2021	Regulatory Status	Novavax completes rolling submission to the Health Canada for approval of NVX CoV 2373 for COVID-2019 infections (Prevention) in Canada ^[79] Updated 03 Nov 2021
01 Nov 2021	Regulatory Status	Novavax completes submission to the European Medicines Agency for conditional approval of NVX CoV 2373 for COVID-2019 infections (Prevention) in European Union ^[79] Updated 03 Nov 2021
29 Oct 2021	Regulatory Status	Novavax completes rolling submission to the Therapeutic Goods Administration (TGA) for provisional approval of NVX CoV 2373 for COVID-2019 infections (Prevention) in Australia ^[86] Updated 02 Nov 2021
27 Oct 2021	Regulatory Status	Novavax plans to complete the rolling submission including complete CMC data package to the US FDA for COVID-2019 infections (Prevention) by the end of 2021 ^[90] ^[109] Updated 04 Jan 2022
27 Oct 2021	Regulatory Status	Novavax completed the rolling submission to the UK MHRA for COVID-2019 infections (prevention) in October 2021 ^[109] Updated 29 Oct 2021
24 Sep 2021	Regulatory Status	Serum Institute of India and Novavax files a regulatory submission to the World Health Organization (WHO) for emergency use listing (EUL) of NVXCoV 2373 ^[58] Updated 27 Sep 2021
05 Aug 2021	Regulatory Status	Novavax and Serum Institute of India announces intention to file for World Health Organisation Emergency Use Listing in August 2021 ^[59] Updated 08 Nov 2021
05 Aug 2021	Scientific Update	Adverse events and immunogenicity data from a phase II portion of phase I/II trial in COVID-2019 infections released by Novavax ^[150] Updated 12 Aug 2021
05 Aug 2021	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in India, India, Indonesia, Philippines (IM) ^[59] Updated 09 Aug 2021
04 Aug 2021	Regulatory Status	Novavax plans to complete the rolling submission to the EMA for COVID-2019 infections (prevention) by third quarter of 2021 ^[18] Updated 03 Nov 2021
18 Jun 2021	Scientific Update	Adverse events and immunogenicity data from a phase III trial in COVID-19 infections released by Novavax ^[125] ^[124] Updated 18 Jun 2021
14 Jun 2021	Scientific Update	Updated efficacy and adverse events data from a phase III trial in COVID-2019 infections released by Novavax ^[133] ^[132] Updated 18 Jun 2021
11 Jun 2021	Scientific Update	Pharmacodynamics data from a preclinical trial in COVID-2019 infections released by Novavax ^[153] Updated 18 Jun 2021
10 May 2021	Regulatory Status	Novavax plans to file for authorization with the US FDA and the European Medicines Agency (EMA), in the third quarter of 2021 ^[21] Updated 08 Nov 2021
10 May 2021	Regulatory Status	Novavax announces intention to file for authorisation for COVID-2019 infections with the UK Medicines and Healthcare products Regulatory Agency (MHRA), in the third-quarter of 2021 ^[21] Updated 29 Oct 2021
10 May 2021	Trial Update	Serum Institute of India completes enrolment in its phase II/III clinical trial for COVID-2019 infections in India Updated 30 May 2021
10 May 2021	Trial Update	Novavax and Serum Institute of India completes enrolment in its II/III trial for COVID-2019 infections (Prevention) in India ^[21] Updated 16 May 2021
05 May 2021	Scientific Update	Updated immunogenicity data from a phase IIb trial in COVID-2019 infections (Prevention) released by Novavax ^[142] Updated 11 May 2021
14 Apr 2021	Trial Update	University of Oxford plans a phase II Com-COV2 trial for COVID-2019 infections (Prevention) in United Kingdom in April 2021 (EudraCT2021-001275-16) ^[164] Updated 21 Sep 2021
31 Mar 2021	Trial Update	Takeda completes enrolment in its phase I/II trial for COVID-2019 infections in Japan (NCT04712110) ^[21] ^[93] Updated 16 May 2021
27 Mar 2021	Phase Change - II/III	Phase-II/III clinical trials in COVID-2019 infections (Prevention) in India (IM) ^[21] Updated 16 May 2021
23 Mar 2021	Patent Information	Novavax has patent protection for NVX CoV 2373 in USA (Novavax FORM 10-K, March 2021) ^[156] Updated 17 May 2021
12 Mar 2021	Trial Update	University of Oxford initiates a phase II Com-COV2 trial in COVID-2019 infections (Prevention) in United Kingdom (ISRCTN27841311) Updated 21 Sep 2021
11 Mar 2021	Scientific Update	Updated immunogenicity data from a phase III trial in COVID-209 infections (Prevention) released by Novavax ^[134] Updated 16 Mar 2021
11 Mar 2021	Scientific Update	Updated safety and immunogenicity data from a phase IIb trial in COVID-2019 infections (Prevention) released by Novavax ^[134] Updated 16 Mar 2021
03 Mar 2021	Regulatory Status	Novavax files an open IND application with the US FDA for COVID-2019 infections ^[69] Updated 03 Mar 2021
01 Mar 2021	Regulatory Status	Novavax plans filing for emergency use authorisation (EUA) of NVX CoV 2373 for COVID-2019 infections in the second quarter of 2021 ^[69] Updated 09 Aug 2021
01 Mar 2021	Patent Information	Novavax has patent pending for NVX CoV 2373 in World (Novavax FORM 10-K, March 2021) ^[156] Updated 17 May 2021
01 Mar 2021	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in Australia (IM) ^[69] Updated 03 Mar 2021
01 Mar 2021	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in New Zealand (IM) ^[69] Updated 03 Mar 2021
01 Mar 2021	Scientific Update	Adverse events data from a phase III trial in COVID-2019 infections (Prevention) released by Novavax ^[69] Updated 03 Mar 2021
24 Feb 2021	Phase Change - I/II	Phase-I/II clinical trials in COVID-2019 infections (Prevention) in Japan (IM) (NCT04712110) ^[152] Updated 25 Feb 2021
22 Feb 2021	Trial Update	Novavax completes enrolment in the PREVENT-19 trial for COVID-2019 infections (Prevention) in Mexico and US ^[121] Updated 24 Feb 2021
04 Feb 2021	Regulatory Status	Takeda expects approval of NVX CoV 2373 in Japan in FY2021 ^[165] Updated 20 Apr 2022
04 Feb 2021	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in United Kingdom, United Kingdom, USA, European Union (IM) ^[110] Updated 08 Feb 2021
03 Feb 2021	Regulatory Status	Novavax announces intention to submit regulatory applications to Government of Switzerland for COVID-2019 infections ^[23] Updated 05 Feb 2021
03 Feb 2021	Trial Update	Novavax plans clinical trial for COVID-2019 infections in Switzerland ^[23] Updated 05 Feb 2021
02 Feb 2021	Phase Change - Preregistration	Preregistration for COVID-2019 infections (Prevention) in Canada (IM) in February 2021 ^[111] Updated 08 Feb 2021
02 Feb 2021	Regulatory Status	Novavax files a rolling submission application with Health Canada in Canada for COVID-2019 infections (Prevention) ^[111] Updated 04 Feb 2021
28 Jan 2021	Scientific Update	Interim immunogenicity and adverse events data from a phase III trial in COVID-209 infections (Prevention) released by Novavax ^[131] Updated 02 Feb 2021
28 Jan 2021	Scientific Update	Updated immunogenicity data from a phase IIb trial in COVID-2019 infections (Prevention) released by Novavax ^[131] Updated 02 Feb 2021
22 Jan 2021	Regulatory Status	Novavax intends to receive authorisation from Canada’s regulatory agency by second quarter of 2021 ^[24] Updated 24 Feb 2022
22 Jan 2021	Regulatory Status	Novavax announced intention to launch NVX CoV 2373 in Canada ^[24] Updated 27 Jan 2021
22 Jan 2021	Regulatory Status	Serum Institute of India announces intention to submit NDA to Drug Controller General of India for COVID-2019 infections (Prevention) Updated 22 Jan 2021
22 Jan 2021	Trial Update	Serum institute of India plans a phase III trial for COVID-2019 infections (Prevention) in India Updated 22 Jan 2021
15 Jan 2021	Trial Update	Takeda plans a phase I/II trial for COVID-2019 infections (Prevention) (IM) (NCT04712110) Updated 25 Feb 2021
15 Jan 2021	Phase Change - Preclinical	Preclinical trials in COVID-2019 infections (Prevention) in Japan (IM) (NCT04712110) Updated 07 Feb 2021
12 Jan 2021	Regulatory Status	Novavax intends to commercialise vaccine in United Kingdom and in Europe ^[25] Updated 13 Jan 2021
08 Jan 2021	Regulatory Status	Novavax announces intention to submit regulatory filings with the TGA, for COVID-2019 infections (Prevention), in Australia ^[26] Updated 11 Jan 2021
28 Dec 2020	Phase Change - III	Phase-III clinical trials in COVID-2019 infections (In adults, In children, In adolescents, Prevention) in USA (IM) ^[120] (NCT04611802) ^[126] Updated 30 Dec 2020
28 Dec 2020	Phase Change - III	Phase-III clinical trials in COVID-2019 infections (Prevention) in Puerto Rico (IM) (NCT04611802) ^[126] Updated 30 Dec 2020
27 Dec 2020	Phase Change - III	Phase-III clinical trials in COVID-2019 infections (In adults, In children, In adolescents, Prevention) in Mexico (IM) ^[120] ^[26] (NCT04611802) Updated 11 Jan 2021
16 Dec 2020	Regulatory Status	Novavax plans to make regulatory submissions with New Zealand's Medsafe for COVID 2019 infections (Prevention) ^[87] Updated 21 Dec 2020
02 Dec 2020	Trial Update	Novavax completes enrolment in its phase II trial for COVID-2019 infections (prevention) in South Africa ^[130] Updated 02 Dec 2020
02 Dec 2020	Trial Update	Novavax completes enrolment in its phase III trial for COVID-2019 infections (prevention) in United Kingdom (NCT04583995) (EudraCT2020-004123-16) ^[130] Updated 02 Dec 2020
30 Nov 2020	Trial Update	Novavax plans a pivotal phase III trial for COVID-2019 infections (Prevention)in December 2020 in USA and Mexico ^[122] (NCT04611802) (2019nCoV301) ^[130] Updated 30 Dec 2020
09 Nov 2020	Regulatory Status	NVX CoV 2373 receives Fast Track designation for COVID-2019 infections [IM,Injection] (Prevention) in USA ^[113] Updated 12 Nov 2020
27 Oct 2020	Regulatory Status	The US government selects NVX CoV 2373 for Operation Warp Speed ^[122] Updated 29 Oct 2020
28 Sep 2020	Regulatory Status	Novavax announces intention for regulatory submissions for licensure in the UK and the EU for COVID-2019 infections ^[135] Updated 28 Sep 2020
24 Sep 2020	Phase Change - III	Phase-III clinical trials in COVID-2019 infections (Prevention) in United Kingdom (IM) ^[135] Updated 28 Sep 2020
02 Sep 2020	Scientific Update	Efficacy and safety data from phase I portion of phase I/II trial in COVID-2019 infections published in New England Journal of Medicine (NEJM-2020) ^[123] ^[149] Updated 20 Jan 2021
24 Aug 2020	Phase Change - I/II	Phase-I/II clinical trials in COVID-2019 infections (Prevention) in USA (IM) ^[143] Updated 26 Aug 2020
17 Aug 2020	Trial Update	Novavax initiates a phase II trial in COVID-2019 infections (Prevention) in South Africa (IM) (NCT04533399) Updated 04 Mar 2022
17 Aug 2020	Phase Change - II	Phase-II clinical trials in COVID-2019 infections (Prevention) in South Africa (IM) ^[141] Updated 20 Aug 2020
14 Aug 2020	Trial Update	Novavax and UK government plans a phase III trial for COVID-2019 infections in UK in third quarter of 2020 ^[29] Updated 28 Sep 2020
14 Aug 2020	Licensing Status	Novavax and UK government signs Heads of Terms for purchase of NVX CoV 2373 and phase III trial in COVID-2019 infections ^[29] Updated 19 Aug 2020
11 Aug 2020	Licensing Status	NVX CoV 2373 licensed to Serum Institute of India and certain low- and middle-income countries (LMIC) for COVID-19 infections ^[31] Updated 11 Aug 2020
07 Aug 2020	Licensing Status	NVX CoV 2373 licensed to Takeda by Novavax, and both agree to co-develop and co-promote NVX CoV 2373 for COVID-2019 infections, in Japan (9300070; 9300165) Updated 13 Aug 2020
04 Aug 2020	Scientific Update	Adverse events and immunogenicity data from a phase I portion of a phase I/II trial in COVID-2019 infections released by Novavax ^[145] Updated 10 Aug 2020
04 Aug 2020	Scientific Update	Pharmacodynamics data from preclinical studies in COVID-2019 infections released by Novavax ^[145] Updated 10 Aug 2020
07 Jul 2020	Regulatory Status	The US government selects NVX CoV 2373 for Operation Warp Speed ^[157] Updated 16 Sep 2020
07 Jul 2020	Regulatory Status	Novavax announces intention to submit regulatory filings with the US FDA for COVID-2019 infections (Prevention) ^[157] Updated 09 Jul 2020
02 Jul 2020	Regulatory Status	Novavax plans to launch NVX CoV 2373 for COVID-2019 infections (Prevention) Updated 07 Jul 2020
04 Jun 2020	Trial Update	Novavax plans a phase II/III trial for COVID-2019 infections (Prevention) ^[160] Updated 09 Jun 2020
11 May 2020	Trial Update	Novavax plans a phase I trial for COVID-2019-infections (Prevention) in Australia (IM) in May 2020 (NCT04368988) ^[166] Updated 17 May 2020
06 May 2020	Phase Change - I/II	Phase-I/II clinical trials in COVID-2019 infections (Prevention) in Australia (IM) (NCT04368988) Updated 17 May 2020
08 Apr 2020	Scientific Update	Pharmacodynamics data from a preclinical study in COVID-2019 infections released by Novavax ^[154] Updated 14 Apr 2020
06 Apr 2020	Licensing Status	Emergent BioSolutions and Novavax enters into a manufacturing and supply agreement for Coronavirus vaccine ^[34] Updated 06 Apr 2020
26 Feb 2020	Phase Change - Preclinical	Preclinical trials in COVID-2019-infections (Prevention) in USA (IM) ^[167] Updated 02 Mar 2020

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NVXCoV 2373

At a glance

Highest Development Phases

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Development Overview

Introduction

Company Agreements

Key Development Milestones

Patent Information

Drug Properties & Chemical Synopsis

Table of Contents

Biomarkers Sourced From Trials

Biomarker

Development Status

Summary Table

Commercial Information

Involved Organisations

Brand Names

Scientific Summary

Adverse Events

Pharmacodynamics

Immunogenicity

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Brand Name	Organisations	Indications	Countries
COVOVAX	Serum Institute of India	COVID 2019 infections	Bangladesh, India, Indonesia
Covovax	Serum Institute of India, Novavax	COVID 2019 infections	Philippines, South Africa, Thailand
Nuvaxovid	Novavax, Takeda, SK Bioscience	COVID 2019 infections	USA, Japan, South Korea, Taiwan, New Zealand, Canada, United Kingdom, Australia, Singapore, United Arab Emirates, European Union

Welcome to AdisInsight

Welcome to AdisInsight

NVXCoV 2373

NVXCoV 2373

At a glance

Highest Development Phases

Most Recent Events

Development Overview

Introduction

Company Agreements

Key Development Milestones

Patent Information

Drug Properties & Chemical Synopsis

Table of Contents

Biomarkers Sourced From Trials

Biomarker

Trial Landscape

Development Status

Summary Table

Commercial Information

Involved Organisations

Brand Names

Related Safety Reports

Scientific Summary

Adverse Events

Pharmacodynamics

Immunogenicity

Therapeutic Trials

Future Events

Development History

References

Legal