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Erenumab - Amgen/Novartis

Drug Profile

Erenumab - Amgen/Novartis

Alternative Names: Aimovig; AMG-334; Erenumab-aooe

Latest Information Update: 28 Jun 2021

At a glance

  • Originator Amgen
  • Developer Amgen; Novartis; Rigshospitalet
  • Class Antimigraines; Monoclonal antibodies
  • Mechanism of Action Calcitonin gene-related peptide receptor antagonists
  • Orphan Drug Status

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

    No
  • New Molecular Entity Yes

Highest Development Phases

  • Marketed Migraine
  • Phase II Headache; Rosacea; Trigeminal neuralgia
  • Discontinued Hot flashes

Most Recent Events

  • 28 Jun 2021 No recent reports of development identified for phase-I development in Migraine(In adolescents, In children) in USA
  • 23 Jun 2021 Registered for Migraine (Prevention, In adults) in Japan (SC)
  • 23 Jun 2021 Pooled efficacy and safety data from phase II and phase III in Migraine released by Amgen

Development Overview

Introduction

Erenumab is a fully human monoclonal antibody that acts as a calcitonin gene-related peptide (CGRP) receptor antagonist, being developed by Amgen and Novartis, for the prevention of migraine and post-traumatic headache. CGRP is expressed throughout the peripheral and central nervous system, where it is involved in controlling vasodilation and transmission of nociceptive information. Its vasodilatory effects play a key role in migraine pathophysiology, and are also thought to be involved in the development of hot flashes in menopausal women. The drug is launched in Canada, EU, Iceland, Liechtenstein, Norway, Switzerland, the US, Spain and is approved in Australia, Singapore, Japan and United Arab Emirates. Erenumab formulated as 140mg injection is approved for prevention of migraine in the US. Clinical development for the prevention of migraine is underway worldwide. Clinical development for the prevention of trigeminal neuralgia, headache and rosacea is ongoing in Denmark.

Development for hot flashes was discontinued in the US and for migraine in Belgium.

Erenumab was the first lead product to arise out of Amgen's CGRP-antagonist research programme [see AdisInsight Drug profile 800036728].

As at June 2021, no recent reports of development had been identified for phase-I development in Migraine (In adolescents, In children) in USA.

Company Agreements

In April 2019, Amgen issued a notice of termination of the collaboration agreement with Novartis for erenumab (Aimovig®). Amgen claimed that the notice was issued due to material breach of the collaboration agreement. Following this, Novartis filed a lawsuit to confirm the legal merit of Amgen’s right to terminate the agreement. Hence, the collaboration will not be terminated until the final announcement of court’s decision. Earlier in April 2017, Amgen had expanded its commercial collaboration with Novartis for erenumab. The companies agreed to co-commercialise erenumab in the US. Amgen retained exclusive commercialisation rights in Japan. Novartis gained exclusive rights to commercialise erenumab in Canada, and retained its existing commercialisation rights in rest of the world. The companies will continue global co-development. Under the terms of the agreement, Amgen will receive milestone payments from Novartis. Novartis will share US commercialisation costs with Amgen. Amgen will book sales of erenumab in the US, and will pay a royalty to Novartis on net sales in the US. Novartis will book sales in the rest of the world, excluding Japan, and will pay Amgen royalties on the net sales in those countries. Amgen will book sales in Japan, since it will remain an exclusive territory for the Company. Novartis will assume agreed upon remaining global development costs up to a cap and share global development costs thereafter. In September 2015, Amgen entered into the global co-commercialisation and co-development collaboration with Novartis in the areas of Alzheimer's disease and migraine. Novartis BACE inhibitor, CNP 520, was to be the lead molecule and each company's pre-clinical BACE (beta-site APP-cleaving enzyme-1) inhibitor programmes will be potential follow-ons. Amgen will make upfront and milestone payments, and will be responsible for disproportional research and development costs for an agreed-upon period followed by a 50/50 cost and profit share arrangement. Novartis will receive global co-development rights and commercial rights outside of the US, Canada and Japan to Amgen's migraine portfolio programme, including AMG 334 and AMG 301, as well as an option to commercialise an additional early-stage Amgen molecule in these territories. In exchange for territory rights, Novartis will fund disproportional amounts of the global R&D expenses for an agreed-upon period on the migraine programmes and pay Amgen double-digit royalties on sales. [1] [2] [3]

Key Development Milestones

Migraine

In March 2019, the US FDA approved the use of erenumab formulated single-dose 140 mg Sureclick®autoinjector device and 140 mg prefilled syringe for prevention of migraine. An a supplemental BLA seeking approval was submitted earlier in June 2018 by Amgen [4] [5] .

In February 2020, an independent appeal panel ruled that it was required of the National Institute for Health and Care Excellence (NICE), to request evidence-based data establishing the effectiveness of erenumab, in a subgroup of patients with chronic migraine. The independent appeal panel upheld one appeal point, which was that the committee unreasonably failed to consider the cost-effectiveness of erenumab, as opposed to the best supportive care in people with chronic migraine who could not benefit from the comparator drug (botulinum toxin) or when it was contra-indicated. The appeal was submitted jointly by the British Association for the Study of Headache and the Association of British Neurologists against the final draft guidance (FAD) for erenumab, which did not recommend the drug, within its marketing authorisation, for prevention of migraine in adults who had a minimum of four migraine days per month. The appeal panel also dismissed other points in the appeal, in December 2019. Earlier, in January 2019, Novartis reported that NICE in its initial decision, did not recommend the routine usage of erenumab on the National Health Service (NHS), for the prevention of migraine in adults. NICE announced that the evidence showed erenumab as a clinically effective treatment. However, the clinical trial evidence for the drug did not fully reflect patients seen in the NHS, nor did it include all the relevant comparisons with other drugs and outcomes. Hence, the cost-effectiveness estimates for erenumab were higher than what NICE deemed as acceptable when there was substantial uncertainty in the evidence. Moreover, there was not enough evidence to suggest that it was more effective than botulinum toxin type A for people with chronic migraine, which NICE already recommends. Also, there was no evidence to show that erenumab was effective in the long-term in people for whom three previous preventive measures had failed for both the chronic and episodic migraine populations [6] [7] [8] .

In October 2018, Novartis announced that erenumab was approved for migraine in Singapore and the United Arab Emirates [9] .

In July 2018, erenumab (Aimovig™) was launched in the US following approval from the US FDA in May 2018, for its use as an once-monthly self-injection for the prevention of migraine in adults. Erenumab 70mg is to be self-administered once monthly via Amgen's SureClick® autoinjector, and does not require a loading dose. The approval was based on three clinical trials [see below] [10] [11] . In July 2017, a Biologics License Application (BLA) for erenumab was filed with the US FDA. The US FDA had assigned a PDUFA date of May 17, 2018 [12] [13] [14] [15] [16] .

In December 2018, Novartis launched erenumab (Aimovig®) for the prevention of migraine in adults who have at least four migraine days per month as a self-administered, once-monthly injection via Amgen's SureClick® autoinjector in Canada [17] . In August 2018, erenumab (Aimovig®) was approved by Health Canada [18] .

In third quarter of 2018, Novartis launched erenumab for the prevention of migraine in adults in Europe [19] . In July 2018, the European Medicines Agency (EMA), the Swissmedic and the Australian TGA approved erenumab for the prevention of migraine in adults. In June 2018, Novartis received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), recommending approval for the product. The CHMP positive opinion was based on a robust data package, including four phase II and phase III clinical studies of more than 2600 patients with migraine. In June 2017, a Marketing Authorisation Application (MAA) was filed with the European Medicines Agency (EMA) [20] [21] [22] [15] .

In June 2021, Amgen announced that the Japanese Ministry of Health, Labour and Welfare granted marketing approval for Aimovig® (erenumab) for the suppression of onset of migraine attacks in adults. The approval is based on results from phase II (20120309) and phase III (20170609) trial [see below]. Earlier in September 2020, Amgen submitted a marketing authorization application with the Japan Pharmaceuticals and Medical Devices Agency (PMDA) for erenumab for the prevention of migraine [23] [24] .

In June 2021, pooled data from phase II (20120309) and phase III (20170609) trial [see below], released by Amgen [23]

In September 2019, Amgen initiated the phase III (OASIS (CM)) trial to evaluate the efficacy and safety of erenumab in migraine prevention in children (6 to <12 years) and adolescents (12 to <18 years) with chronic migraine (NCT03832998; 20160354; P370-2016; EudraCT2017-002399-23). The randomised, double blind trial intends to enrol 286 participants in the US, Belgium, Finland, Hungary, Italy, Japan, United Kingdom, Canada, Germany, Poland [25] .

In July 2019, Amgen initiated a phase III trial (OASIS PEDIATRIC [EM]) to evaluate the efficacy and safety of erenumab in migraine prevention in children (6 to <12 years) and adolescents (12 to <18 years) with episodic migraine (NCT03836040; 20150125; EudraCT2017-002397-39).The randomised, parallel assignment trial intends to enrol 456 participants in the US, Belgium, Finland, Hungary, Switzerland, United Kingdom, Canada, Germany, Poland, Japan, Italy and may expand to other countries [26] .

In November 2020, Amgen completed a phase III trial to evaluate safety and efficacy of erenumab for prevention of migraine in Japanese patients with episodic migraine and chronic migraine (20170609; NCT03812224). The randomised, double-blind trial was initiated in April 2019 and enrolled 261 patients in Japan [27] . As of June 2021, patients treated with erenumab saw a reduction from baseline in their monthly migraine days [23] .

In January 2020, Novartis Pharmaceuticals completed the phase III EMPOwER trial that evaluated the efficacy and safety of erenumabin countries beyond the US and the EU (CAMG334A2302; NCT03333109). The double-blind, parallel, prospective, randomized trial was initiated in February 2018 and enrolled 900 patients in Argentina, India, Mexico, Philippines, Vietnam, South Korea, Lebanon, Malaysia, Singapore, Taiwan and Thailand [28] .

In January 2018, Novartis reported that the phase III LIBERTY trial met the primary endpoint of percentage of patients treated with erenumab who achieved at least 50% reduction of migraine days compared to placebo including the secondary endpoints (CAMG334A2301; EudraCT2016-002211-18; NCT03096834). The trial evaluated the efficacy and safety of once monthly subcutaneous injection of erenumab 70mg in adult patients with episodic migraine who have failed 2-4 prophylactic treatments. The 12-week open label, double-blind, randomised trial initiated in October 2016, and enrolled 247 patients in Australia, Austria, Belgium, Czech, Denmark, Finland, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, Switzerland and the UK. The trial includes a 156 weeks open label extension phase (OLEP) to evaluate the long-term efficacy of erenumab. The OLEP includes patients who completed the 12-week double-blinded treatment phase (DBTP). Initial data from the study were released in October 2018. Updated efficacy data from the OLEP of the trial were released in July 2019. In May 2019, results from the study were presented at the 71st Annual Meeting of the American Academy of Neurology (AAN-2019) [29] [30] [9] [31] [32] [33] [34] . In October 2020, Amgen announced two-year data of phase III trial that showed sustained efficacy and no increases in adverse events rates [35] .

In November 2016, Amgen reported that the phase III STRIVE trial met its primary endpoint demonstrating statistically significant reductions from baseline in monthly migraine days in patients with episodic migraine treated with either 70mg or 140mg erenumab, when compared with placebo (20120296; NCT02456740; EudraCT2014-004464-38). The randomised, double-blind, placebo-controlled trial was initiated in July 2015, and enrolled 955 patients in the US, Austria, Belgium, Canada, Czech Republic, Finland, Germany, Hungary, Netherlands, Sweden, Slovakia, Poland, Turkey and the UK. The trial was completed in June 2017. The comparative results from the trial that demonstrated a safety profile synonymous with that observed in previous trials, were released in May 2019. In May 2019 and June 2019, Novartis released and presented the updated 52-week data from the trial that exhibited erenumab reduced acute migraine medication days by half in patients, who failed prior preventions at the 71st Annual Meeting of the American Academy of Neurology [36] [37] [38] [39] [40] [41] [42] .

In March 2017, Amgen completed the randomised, double-blind, phase III trial that evaluated the effect of erenumab on the change from baseline in monthly migraine days, in patients with episodic migraine (ARISE; 20120297; NCT02483585; EudraCT2014-004463-20). The trial was initiated in July 2015 and enrolled 577 patients in the US, Denmark, France, Greece, Portugal, Russia, Spain and Switzerland [43] . In September 2016, Amgen reported that the phase III ARISE study had met its primary end point by achieving significant reduction from baseline in monthly migraine days in patients with episodic migraine compared with a placebo at 12 weeks [44] [45] .

In August 2019, Novartis initiated a phase III DRAGON trial to evaluate the safety and efficacy of subcutaneous erenumab in adult patients with migraine (CTRI2020-09-027647; CAMG334A2304; NCT03867201). The randomized and double blind study is designed to enrol approximately 550 patients in China, India, Malaysia, Philippines, Singapore, Taiwan, Thailand, Vietnam and South Korea [46] .

In October 2019, Danish Headache Center (a department in Rigshospitalet), initiated a phase II proof-of-concept study to evaluate efficacy and tolerability of erenumab in patients with trigeminal neuralgia (H-19011013; NCT04054024). The randomised, double blind trial intends to enrol approximately 80 patients in Dentmark [47] .

In January 2015, Amgen completed the randomised, double-blind, placebo-controlled phase IIb trial which evaluated the efficacy and safety of subcutaneous doses of erenumab in the prevention of chronic episodic migraine (20120178; NCT01952574; EudraCT2012-005331-90). The primary endpoint was the change in monthly migraine days from baseline, assessed from weeks 9 to 12. The 12-week trial enrolled 484 patients in the US, Canada, Denmark, Finland, Germany, Sweden and Norway [48] [49] . Patients after completing the 12-weeks double blind phase continued into an open-label extension (OLE) phase to evaluate the efficacy, long-term safety and tolerability of erenumab 70 mg monthly up to five years in 383 patients with episodic migraine. A protocol amendment increased the dose of erenumab to 140 mg monthly to assess long-term safety of the higher dose. In June 2018, Amgen released three-year interim analysis from this five-year study. In September 2019, company released long-term results from the study.In April 2020, long term interm analysis of more than four years was presented at the 72nd Annual Meeting of the American Academy of Neurology (AAN-2020) [50] [51] [20] [52] [53] [54] . In October 2020, Amgen announced five-year data of phase II trial [35] . In April 2021, Amgen presented the updated efficacy and safety results from the trial at the 73rd Annual Meeting of the American Academy of Neurology (AAN-2021) [55] .

In June 2019, Amgen completed a phase II trial that evaluated the safety and efficacy of multiple doses of erenumab for the prevention of episodic migraine (20120309; NCT02630459). The randomised, double blind, placebo control trial was initiated in January 2016, and enrolled 475 patients in Japan [56] . Patients were randomised to receive once-monthly subcutaneous placebo, or erenumab (28 mg, 70 mg or 140 mg) in a 2:1:2:2 ratio. In November 2018, Amgen Astellas Biopharma released positive data of the study [57] .

In April 2016, Amgen completed the randomised, double-blind phase II trial, which assessed the safety and efficacy of erenumab in chronic migraine prevention (20120295; NCT02066415; EudraCT2013-001707-36). The 12-week trial recruited 667 patients in the US, Canada, Czech Republic, Denmark, Germany, Finland, Norway, Poland and Sweden. In September 2017, positive results from a pre-planned sub-analysis of the trial were reported [58] [59] . In May 2017, an open-label extension study was completed that evaluated the long term safety and efficacy of the drug in preventing migraine (20130255; NCT02174861; EudraCT2013-005311-27). The one-year trial was initiated in June 2014, and enrolled 609 chronic migraine patients in the US, Canada, the Czech Republic, Denmark, Finland, Germany, Norway, Poland, Sweden and the UK [60] [61] . In June 2018, Amgen released interim analysis of this one-year OLE study. Updated efficacy results from an exploratory analysis of the OLE were released in May 2019 [38] [52] . In June 2016, Amgen released positive top-line results of a phase II trial of a monthly subcutaneous injection of erenumab (7, 21 and 70mg), wherein the trial met its primary endpoint of reducing monthly mean migraine days as compared with placebo [62] . In May 2019, Amgen presented the efficacy data at the 71th Annual Meeting of the American Academy of Neurology (AAN-2019) [63] .

In May 2018, Amgen initiated a phase I trial to evaluate the safety, tolerability and pharmacokinetics of erenumab, in children and adolescents with migraine (20160172; NCT03499119). The open label trial intends to enrol approximately 60 patients in the US [64] .

In September 2016, Amgen completed a phase I trial, which assessed the pharmacokinetic drug interaction of erenumab and an oral contraceptive containing progestin and estrogen in healthy female volunteers (20150334; NCT02792517). The open-label, single-group trial was initiated in February 2016 and recruited 35 volunteers in the US [65] .

Amgen completed a phase I trial in August 2016, which investigated the effect on blood pressure of erenumab when given in combination with sumatriptan SC in healthy volunteers (NCT02741310; 20140255). The randomised, double-blind trial was initiated in February 2016 and enrolled 30 participants in Belgium. Results from the trial, which revealed that concomitant administration of IV erenumab 140mg with SC sumatriptan had no effect on resting blood pressure, as compared with SC sumatriptan alone, were presented at the 69th Annual Meeting of the American Academy of Neurology (AAN-2017) in April 2017 [66] [67] .

In November 2017, Amgen completed a phase I trial that evaluated the blockade of CGRP receptor by erenumab in preventing PACAP-38 (Pituitary Adenylate Cyclase-Activating Polypeptide-38) induced migraine-like attacks in migraine patients (20140207; NCT02542605). The randomised, double-blind, parallel-assignment, placebo-controlled trial was initiated in November 2015 and enrolled 38 volunteers in the US, Belgium and the Netherlands [68] .

Amgen initiated a randomised, double-blind, placebo-controlled phase I trial in November 2012, to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending subcutaneous doses of erenumab in healthy volunteers and patients with migraine (20101268; NCT01723514). The trial also investigated the effect of multiple doses of erenumab on capsaicin-induced increases in dermal blood flow. The trial enrolled 48 patients in Belgium, and was completed in July 2014 [69] .

Amgen terminated a randomised, double-blind, placebo-controlled phase I trial in November 2013 that was assessing the safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending intravenous and subcutaneous doses of erenumab in healthy volunteers and patients with migraine (20101267; NCT01688739; EudraCT2011-005600-15). The trial, which was initiated in March 2012, was also investigating the effect of single doses of erenumab on capsaicin-induced increases in dermal blood flow. The trial enrolled 60 patients in Belgium [70] .

In December 2019, Danish Headache Center in collaboration with Novartis and Amgen completed a phase II trial that evaluated the safety and efficacy of erenumab in the prophylactic treatment of persistent headache caused due to mild traumatic injury to the head (EudraCT2018-003943-46; NCT03974360). Change in the monthly average number of headache days with moderate or severe intensity from baseline to week 9-12 in patients with persistent post-traumatic headache (PPTH) was the primary endpoint. The exploratory open-label trial was initiated in April 2019 and enrolled 100 participants in Denmark [71] .

Menopausal syndrome

As at May 2018, the indication was not listed on the company pipelines, and the development for this indication appears to be discontinued.

In October 2014, Amgen completed a phase I trial of erenumab in women with menopausal hot flashes (20120180; NCT01890109). The trial was initiated in May 2013 and determined the effects of a single SC dose of erenumab on the frequency and severity of hot flashes. Tolerability, pharmacokinetics and the number of patients who develop anti-erenumab antibodies was also determined. Two dose levels of erenumab were evaluated. The randomised, double-blind trial enrolled 103 patients aged 45 to 65 years in the US [72] .

Cardiovascular safety trial

In April 2017, Amgen completed the phase II Treadmill cardiovascular safety trial that evaluated the effect of erenumab on exercise time during a treadmill test in patients with stable angina (NCT02575833; EudraCT2015-002322-40; 20140254). The randomised, double-blind, placebo-controlled trial was initiated in November 2015 and enrolled 89 patients in the US, Slovakia, Bulgaria, Germany, Latvia, Czech Republic, Poland, New Zealand, Romania, South Africa and Switzerland. In September 2017, positive results from the trial were reported [58] [73] .

Rosacea

In June 2020, Novartis initiated the phase II STOP Ros trial, to assess the efficacy and tolerability of erenumab in the prophylactic treatment of persistent redness and flushing attributed to rosacea (ROS031019; EudraCT2019-003971-20; NCT04419259). The patients will receive monthly subcutaneous injections of erenumab, 140mg at week 0, week 4, week 8. The open-label, single-group trial intends to recruit 30 patients in Denmark [74] .

Patent Information

Novartis holds patents for erenumab in the US and EU. Patent in the US is set to expire in 2031, while patent in the EU will expire in 2029 [75] .

Drug Properties & Chemical Synopsis

  • Route of administration IV, SC
  • Formulation Injection, unspecified
  • Class Antimigraines, Monoclonal antibodies
  • Target Calcitonin gene-related peptide receptor
  • Mechanism of Action Calcitonin gene-related peptide receptor antagonists
  • WHO ATC code

    N02C-D01 (Erenumab)

  • EPhMRA code

    N2C (Anti-Migraine Preparations)

  • Molecular formula C6472 H9964 N1728 O2018 S50
  • CAS Registry Number 1582205-90-0

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Headache Post-traumatic headache Prevention Phase II Denmark SC / Injection Amgen, Novartis 05 Apr 2019
Hot flashes - - Discontinued (I) USA SC / Injection Amgen 21 May 2018
Migraine - In adults, Prevention Marketed USA SC / Injection Amgen, Novartis 18 Jul 2018
Migraine - Prevention Marketed Canada, European Union, Iceland, Liechtenstein, Norway, Spain, Switzerland SC / Injection Novartis 13 Aug 2019
Migraine Erenumab 140 mg Sureclick® autoinjector device and Erenumab 140 mg prefilled syringe In adults, Prevention Registered Japan, USA SC / Injection Amgen 23 Jun 2021
Migraine - Prevention Registered Australia, Singapore, United Arab Emirates SC / Injection Novartis 29 Oct 2018
Migraine - In adolescents, In children, Prevention Phase III Belgium, Canada, Finland, Germany, Hungary, Italy, Japan, Poland, Switzerland, USA, United Kingdom SC / Injection Amgen 05 Sep 2019
Migraine - Prevention Phase III Russia, Turkey SC / Injection Amgen 20 Jul 2015
Migraine - Prevention Phase III Argentina, China, India, Lebanon, Malaysia, Mexico, Philippines, South Korea, Taiwan, Thailand, Vietnam SC / Injection Novartis 26 Aug 2019
Migraine - In adolescents, In children No development reported (I) USA unspecified / unspecified Amgen 28 Jun 2021
Migraine - - Discontinued (I) Belgium IV / unspecified Amgen 22 May 2018
Rosacea - - Phase II Denmark SC / Injection Novartis 09 Jun 2020
Trigeminal neuralgia - - Phase II Denmark unspecified / unspecified Rigshospitalet 28 Oct 2019

Commercial Information

Involved Organisations

Organisation Involvement Countries
Amgen Originator USA
Amgen Owner USA
Amgen Market Licensee Japan, USA
Novartis Market Licensee Canada, Europe, USA
Novartis Licensee World
Rigshospitalet Collaborator Denmark
Amgen Astellas BioPharma Collaborator Japan

Brand Names

Brand Name Organisations Indications Countries
Aimovig Novartis, Amgen Migraine Canada, European Union, Japan, USA

Credit Suisse Market Status

Indication Region Company Phase Expected Launch Year Probability of Success% Patent Expiry Year Expected Generic Entry Last Update
Migraine ex US Amgen, Novartis Marketed 2018 100 2029 18 Dec 2030 01 Feb 2021
Migraine Japan Amgen, Novartis Filed 2021 99 - - 01 Feb 2021
Migraine US Amgen, Novartis Marketed 2018 100 2031 - 01 Feb 2021

Credit Suisse Financial Forecast

Indication Region 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 Last Update
Migraine ex US 0 0 8 103 145 280 400 500 580 625 01 Feb 2021
Migraine Japan 0 0 0 0 0 60 167 192 211 228 01 Feb 2021
Migraine US 0 0 123 306 428 575 735 795 840 910 01 Feb 2021
Total 0 0 131 409 573 915 1302 1487 1631 1763

Scientific Summary

  • Adverse Events Frequent: Respiratory tract infections; Sinusitis
    Occasional: Abdominal pain; Arthralgia; Back pain; Constipation; Dental caries; Fatigue; Gastroenteritis; Influenza virus infections; Injection site pain; Nasopharyngitis; Pharyngitis

Adverse Events

Phase III

In the phase III STRIVE trial in 955 patients with episodic migraine, subcutaneous 70mg or 140mg of erenumab showed a safety profile, which was consistent with previously reported studies. The safety profile was also comparable to placebo across both the treatment arms. Nasopharyngitis, upper respiratory tract infection and sinusitis were observed as the most frequently reported adverse events [39] [40] .

Erenumab was found to be safe and effective in prevention of migraine, including those who live with particularly difficult-to-treat migraine. Results from the phase IIIb LIBERTY trial for erenumab conducted in 246 patients with episodic migraine showed that there were no adverse events leading to discontinuation of treatment in the treatment arm while 0.8% of those in the placebo group experienced adverse events leading to discontinuation of treatment. Injection site pain (5.9%), back pain (4.2%) and nasopharyngitis (4.2%) were the most common adverse events observed. The tolerability and safety profile of erenumab was found to be similar to that of placebo [9] [31] [34] .

The phase III ARISE study demonstrated a similar safety profile of erenumab compared with the placebo and consistent with previously reported studies. The most common adverse events reported were upper respiratory tract infection, injection site pain and nasopharyngitis. The trial enrolled 577 patients who experienced between four and 14 migraine days each month, with an average of eight migraine days per month at baseline and were randomised to receive either placebo or erenumab 70mg subcutaneously, once monthly [81] [44] [43] .

Phase II

The phase II Treadmill Cardiovascular safety trial, the most frequent treatment-emergent adverse events (reported in >2% of patients) were headache (4.5%) and viral upper respiratory infection (4.5%) in the erenumab group, and were hypotension (4.5%), influenza (4.5%) and viral infection (4.5%) in the placebo group. Adverse events were reported by 14% of erenumab -treated patients and by 27% of placebo patients and were consistent with the known safety profile of erenumab. The trial evaluated the effect of erenumab on exercise time during a treadmill test in 89 subjects with stable angina [58] [73] .

Updated resulted from the open-label treatment phase (OLTP) of the phase II trial of AMG 334 in patients for prevention of episodic migraine showed that safety was comparable with that observed in full population during randomised phase of the trial. Exposure-adjusted patient incidence of AEs and serious AEs during OLTP were 92.3 and 2.6 per 100 subject-years, respectively; This was lower than that observed for placebo during double-blind treatment period (DBTP). One fatality (“death unattended”) occurred during safety follow-up period whenAMG 334 was administered and was considered unrelated to AMG 334 by the investigator. Previously, results from the interim analysis of more than four years from a five-year open-label treatment period study demonstrated no new safety signals nor increases in adverse event (AE) or serious AE (SAE) incidence and was well tolerated and safe in patients (n = 383) with episodic migraine. Exposure-adjusted AE and SAE incidence rates were 124.9/100-patient-years and 3.8/100-patient-years. The most frequent AEs reported were nasopharyngitis (10.9/100-patient-years), upper respiratory tract infection (6.8/100-patient-years), and influenza (4.7/100-patient-years). Increase in constipation with long term treatment was not observed. Treatment was discontinued by 19 patients due to AE. Results of a three-year interim analysis from a five-year, open-label extension phase of the randomised, double-blind, placebo-controlled phase IIb 20120178 trial in 383 patients with episodic migraine demonstrated that erenumab had a safety profile consistent with the spectrum and rate of adverse events (AEs) seen in shorter-term placebo-controlled studies, no new AEs and no new causally-related serious AEs. The most frequent AEs were viral upper respiratory tract infection, upper respiratory tract infection, sinusitis, influenza and back pain. There was no increase in cardiovascular events over time and no meaningful changes in systolic/diastolic blood pressure or heart rate up to the ~3.2 year follow-up. Interim data of the open-label portion of erenumab 70mg monthly subcutaneous injection demonstrated safety and tolerability profile similar to that observed in the blinded phase. Arthralgia, influenza, fatigue, nasopharyngitis and back pain were the most commonly reported AEs and there were no grade 4 or 5 AEs. There was one treatment-related serious adverse event amongst others reported in 13 patients. Less than 5% of patients discontinued the trial due to adverse events. A monthly subcutaneous injection of erenumab (7, 21 and 70mg) demonstrated dose tolerability profile similar to placebo across all dosing groups, without any Grade 4 or 5 adverse events (AEs), in a 12-week phase II trial. Fatigue, influenza, nasopharyngitis, arthralgia and back pain were the most commonly reported AEs. The double-blind, randomised (3:2:2:2) trial assessed the efficacy and safety of erenumab for the prevention of episodic migraine in 483 patients [55] [50] [51] [52] [35] [49] [53] [54] .

In a phase II randomised, double bind trial, once in month subcutaneous erenumab showed safety profile similar to placebo in both treatment arms, 70mg and 140mg. Treatment with erenumab did not lead to any adverse event in greater than five percent of patients treated with erenumab. The most common adverse events (in placebo, 70 mg erenumab, 140 mg erenumab groups, respectively) were injection site pain (1.1%, 3.7%, 3.7%), upper respiratory tract infection (1.4% , 2.6%, 3.2%) and nausea (2.5%, 2.1%, 3.2%). The trial enrolled 667 patients of chronic migraine [61] [62] [59] .

Interim results of the open-label extension 20130255 study in 609 patients with chronic migraine showed that the safety results of erenumab after one year were consistent with the established safety profile in previous studies. The most frequent adverse events (AEs) greater than 2 per 100-subject-years were viral upper respiratory tract infection, upper respiratory tract infection, sinusitis, arthralgia and migraine [52] [60] .

Positive results of the randomised, six-month phase II trial in Japanese patients (n = 475) for the prevention of episodic migraine observed similar frequencies of adverse events and serious adverse events across erenumab and placebo groups. The most frequently reported adverse events (in at least 2% of patients in any group) were nasopharyngitis, constipation, pharyngitis, back pain, dental caries, gastroenteritis and upper abdominal pain [57] [56] .

Pooled analysis:

Data from pooled analysis of four placebo-controlled trials showed that erenumab had no significant effect on systolic and diastolic blood pressure over 12 weeks in patients with migraine as well as 24-hours continuously recorded blood pressure in healthy volunteers. Blood pressure remained stable over 12 weeks with no significant difference as compared with placebo treated patients. At week 12, mean (SD) change in systolic blood pressure (SBP) was -0.5 (10) and -1.0 (9.8) mmHg for erenumab; 70mg and 140mg, respectively compared with -0.4 (9.6) mmHg in placebo group. Mean (SD) change in diastolic blood pressure (DBP) was -0.3 (7.7) and -0.4 (7.2) mmHg compared with -0.6 (7.1) mmHg in placebo group. In a phase I trial, 24-hour continuously measured blood pressure was not changed in healthy volunteers receiving erenumab at 70 and 140mg, monthly over 12 weeks [79] [54] [59] [60] [40] [43] .

In both phase II 20120309 and phase III 20170609 trial, the safety and tolerability of erenumab was also consistent with previously available global data. The most commonly reported adverse reactions include constipation, injection site reactions and somnolence at an incidence of 1% or more [23]

Immunogenicity

Summary

Pooled analysis:

Pooled analysis from four placebo-controlled phase II and phase III trial showed that treatment with erenumab was associated with low incidence of anti-erenumab antibodies with high reversal rate without any impact on the efficacy, pharmacokinetic and safety in patients. Incidence of anti-erenumab binding antibodies (BAbs) in serum was 6.3% (56/884) with 70mg. Three patients were found positive for neutralizing antibodies (NAbs) of which two patients were Nab-negative by end of studies. Incidence of BAbs was 2.6% (13/504) with 140mg without any NAb-positive patients. Half of the BAb-positive patients turned BAb-negative by end of study. Change in mean (SD) monthly migraine days compared with baseline at month three in BAb-negative patients was -3.2 (0.2) and -3.6 (0.2) at 70 and 140mg, respectively vs. -3.2 (0.7) and -4.1 (0.8) in BAb-positive patients. Change in mean (SD) monthly migraine days compared with baseline at month six in BAb-negative patients was -3.5 (0.2) and -3.8 (0.2) at 70 and 140mg, respectively vs. -3.2 (0.9) and -5.2 (0.9) in BAb-positive patients. Anti-erenumab binding antibodies (BAbs) had no effect on exposure wherein concentration in BAb-positive patients overlapped with BAb-negative patients at week 12. Anti-erenumab antibodies did not cause any safety issue and no injection-site reactions, hypersensitivity and immune-related disorders were reported [78] [54] [59] [60] [40] [43] .

Therapeutic Trials

Phase III

The phase III STRIVE trial in 955 patients with episodic migraine met its primary endpoint, and statistically significant reduction from baseline in monthly migraine days was observed upon treatment with either 70mg or 140mg erenumab, when compared with placebo. At week 52, patients receiving erenumab 70mg (n=421) or 140mg (n=424) during active treatment phase (ATP) reported –4.2 / –4.6 monthly migraine days (MMD) changes from baseline and –1.1/–1.8 MMD from ATP baseline, respectively. For patients switching from placebo to erenumab change from ATP baseline was reported to be –2.2 and –2.9, respectively. Improvements were also reported in migraine specific medication treatment days. Further 61% of patients on 70mg and 64.9% of patients on 140mg demonstrated a ≥50% responder rates (RR) and 38.5% of patients on 70mg and 40.8% of patients on 140mg achieved a ≥75% RR, 19.8% of patients on 70mg and 21.2% of patients on 140mg achieved 100% RR. At baseline, patients experienced an average of 8.3 migraine days per month. Patients in the erenumab 70mg and 140mg treatment arms showed reductions of 3.2 and 3.7 days from baseline in monthly migraine days, respectively, as compared to a 1.8-day reduction in the placebo arm. Erenumab administration demonstrated reduction in migraine by 50% or greater in 50% patients at 140mg dose and 43% at 70mg dose, compared to 26.6% in placebo group. Odds ratio was noted to be 2.8 and 2.1 respectively for 140 and 70mg; P < 0.001 in both doses, versus placebo. Secondary point of reduction in the number of days of migraine episodes per month using acute migraine-specific medication was noted to be 1.6 days for 140mg, 1.1 days in 70mg dose, compared to 0.2 day placebo; both doses p < 0.001, versus placebo. Reduction in impact of migraine in day-to-day life activities (5.9 points for 140mg; 5.5 points for 70 mg; 3.3 points for placebo; p<0.001 for both doses, versus placebo) was noted as measured by MPFID instrument. Reduction in scores measuring physical impairment (4.8 points for 140 mg; 4.2 points for 70mg, 2.4 points for placebo; p<0.001 for both groups versus placebo) was also noted. Additional results from the trial demonstrated that 52% patients (n=492) out of 955, had history of aura with similar baseline characteristics among groups. In both subgroups, erenumab induced greater reductions in monthly migraine days (MMD) as compared with placebo. The least-squares mean (SE) changes from baseline were -1.5 (0.3) for placebo vs -2.7 (0.3) for 70-mg (p=0.002) and -3.8 (0.3) for 140mg (p<0.001) in patients without aura history, while in patients with aura history, changes were -2.1 (0.3) for placebo vs -3.8 (0.2) for 70mg (p<0.001) and -3.5 (0.3) for 140mg (p<0.001). The responder rates ( ≥ 50% reductions in MMDs) for patients without aura history were 23% (placebo) vs 39% (70mg odds ratio (95% CI): 2.1 (1.3, 3.5); p=0.003) and 49% (140mg OR: 3.3 (2.0, 5.4); p<0.001) and with aura history were 30% (placebo) vs 47% (70mg OR: 2.1 (1.3, 3.3); p=0.001) and 51% (140mg OR: 2.4 (1.5, 3.8); p<0.001). Changes in the respective migraine-specific medication days (MSMD) were -0.1 (0.2) vs -1.3 (0.2) and -2.0 (0.2) for patients without aura history (p<0.001 for both) and -0.3 (0.1) vs -1.0 (0.1) and -1.3 (0.1) for patients with aura history (p<0.001 for both). In an analysis of patients who had failed one or two previous oral preventive migraine medications, erenumab was shown to be superior to placebo in both subgroups. The odds of responding to erenumab increased in those who failed more than two prior preventive medications since the placebo response was attenuated. This indicated that erenumab is effective in those patients who have failed multiple previous preventive medications. The results from the trial showed that patients who received erenumab 70mg or 140mg from week 24 onward displayed an average of 4.2 and 4.6 fewer MMD, respectively, as compared with study baseline (8.3 MMD). Continuous improvements during the active-treatment period (ATP) were witnessed by the patients, with the respective dosages registering 1.1 and 1.8 fewer MMD. An analysis of responder rates from baseline showed that at 70mg or 140mg dosing, more than six of 10 patients displayed 50% fewer MMD, approximately four of 10 patients showed 75% fewer MMD, and one of five patients were completely relieved of migraine, at week 52. The updated results showed that at 52 weeks, 55 % of the patients on 140 mg of erenumab experienced at least 50 % reduction in the number of MMD requiring acute medication. The drug exhibited sustained efficacy in patients with episodic migraine, who failed prior preventions throughout the 52 week period [36] [37] [38] [86] [41] [42] [39] [40] .

In the phase IIIb LIBERTY trial, at week 24, 39.2%, 15.9% and 7.0% patients achieved ≥50%/≥75%/100% reduction in monthly migraine days. The mean change from baseline in monthly migraine days was −2.7 (4.4) and −1.4 (3.0) in MSMD; and −7.6 (8.0), −2.5 (9.2) and −4.0 (9.0) in HIT-6 ™, MPFID-PI and MPFID-EA scores respectively. With sustained use patients experienced sustained efficacy in all outcomes assessed. Patients who switched from placebo to erenumab in the open-label extension phase demonstrated an improvement from the first measurement at week 16 on all outcomes assessed [29] . Patients receiving once monthly subcutaneous injection of erenumab 140mg had nearly three-fold higher odds of having their migraine days cut by at least 50%, with more than twice as many patients taking erenumab achieving this reduction compared to placebo (weeks 9-12: 30% with erenumab, 14% with placebo, p=0.002, odds ratio 2.7). In the study, patients receiving erenumab had statistically significant and clinically meaningful improvements from baseline compared to placebo across all secondary endpoints: reduction in monthly migraine days; decrease in monthly acute migraine-specific drug use; 75% or greater reduction in monthly migraine days (12% vs. 4%; odds ratio 3.2, p=0.025); migraine days were cut by 100% in 6% of patients on erenumab vs no patients (0%) on placebo (secondary endpoint); a substantial reduction in monthly migraine days (MMD) (1.8 vs 0.2 fewer MMD, p=0.004, secondary endpoint) was observed; significant reductions in the number of days per month were reported in erenumab arm using acute migraine-specific medication (1.3 reduction vs 0.5 day increase; p<0.001, secondary endpoint); improved physical functioning and ability to complete everyday activities, such as chores and getting out of bed, compared to placebo (Migraine Physical Function Impact Diary [MPFID] physical impairment scale, 3.5 point difference, p= 0 003; everyday activities scale, 3.9 point difference, p<0 001). Updated results from the open label extension phase (OLEP) of the trial displayed sustained efficacy for erenumab 140mg in lowering monthly MMD at 13-24 weeks in episodic migraine patients with 2-4 prior failures. A sustained reduction in physical impairment and an improved ability to participate in daily activities was exhibited by patients on erenumab, at week 24 [30] [9] [80] [31] [32] [33] [34] .

Topline results from the phase III ARISE trial demonstrated that the primary endpoint in the trial was met with a statistically significant 2.9-day reduction from baseline in monthly migraine days in patients in the erenumab arm compared with a 1.8-day reduction in the patients in placebo arm. The trial enrolled 577 patients who experienced between four and 14 migraine days each month, with an average of eight migraine days per month at baseline and were randomised to receive either placebo or erenumab 70mg subcutaneously, once monthly [81] [44] [43] .

Phase II:

Updated resulted from the open-label treatment phase (OLTP) of the phase II trial of AMG 334 in patients for prevention of episodic migraine showed that five years of treatment demonstrated consistent and sustained response. Mean (SD) change in monthly migraine days (MMD) from DBTP baseline of 8.5(2.5) days was –4.8(3.9) at week 64 (mean of last 4 weeks of 1-year OLTP; N=129), and –5.3(3.9) at week 268 (mean of last 4 weeks of 5-year OLTP). Patients achieving MMD response at week 64/268 was 62%/69% for achievement of =50% reduction; 41%/48% for =75% reduction; and 26%/36% for 100% reduction. In acute migraine-specific medication (AMSM) users at baseline (6.1[2.7] treatment days/month), mean(SD) change in AMSM days was –3.2(3.5) at week 64 and –4.4(3.3) at week 268. Clinically meaningful improvements were observed in HIT-6TM: 68%/72% of patients achieved =5-point reduction from baseline at weeks 64/268. Previous results from the five-year open-label treatment period study demonstrated sustained efficacy in patients with episodic migraine. 4.5 year data reported that 77% of the patients who continued on treatment experienced at least a 50% reduction in monthly migraine days (MMD) at the last month of assessment and 33% of patients who continued on treatment achieved a 100% reduction, and 56% achieved a 75% decrease in MMD. Patients who shifted from 70mg to 140mg specifically, had an average of 5.8 fewer MMD, as compared with study baseline (8.7 MMD). A monthly subcutaneous injection of erenumab (7, 21 and 70mg) met its primary endpoint by reducing monthly mean migraine days (mean baseline = 8.7 days), measured at week 12, in a phase II trial. Statistically significant reductions in monthly migraine days (3.4 vs 2.28; p = 0.021), in monthly headache days (-3.54 vs -2.39) and monthly migraine-specific medication use days (-1.64 vs. -0.69) was observed in patients randomised to 70mg dose group as compared with placebo. Additionally, statistically significant increase in the 50% responder rate was shown by the drug (47% vs 30% placebo; secondary endpoint). The double-blind, randomised (3:2:2:2) trial assessed the efficacy and safety of erenumab for the prevention of episodic migraine in 483 patients [55] [51] [49] [54] .

A phase II double-blind study met its primary endpoint of reduction in monthly migraine days upon once in a month subcutaneous administration of 70mg or 140mg of erenumab in patients with chronic migraine. Erenumab demonstrated a statistically significant reduction in monthly migraine days compared with placebo in patients with chronic migraine. At week 12, a reduction of 50 percent or more in number of monthly migraine days was observed in 40 percent and 41 percent of individuals receiving 70 mg and 140 mg doses erenumab, respectively, compared with 24 percent of those receiving placebo (both p < 0.001). Across both doses, patients observed a statistically significant 6.6-day reduction from baseline in monthly migraine days compared with 4.2 days observed in those on placebo (p < 0.001). Reductions in monthly acute migraine-specific medication days were 3.5 days and 4.1 days in the 70 mg and 140 mg groups, respectively, compared to a 1.6-day reduction the placebo group (both doses p < 0.001 versus baseline). Compared to a 55.2-hour reduction versus baseline in the placebo group, reductions were 64.8 hours (p = 0.28) for 70 mg erenumab and 74.5 hours (p = 0.03) for 140 mg erenumab. Days requiring acute pain-relief medications were also significantly reduced in both dosage arms (2.1-day reduction for placebo, compared to 5.4 days for erenumab 70 mg and 4.9 for erenumab 140 mg; both p < 0.001 versus placebo). Both doses of erenumab were associated with significant improvements in health-related quality of life, headache impact, disability, and pain interference outcome measurements, compared to placebo. In a pre-specified sub-analysis, at the end of the 12-week study, patients who had failed two or more prior treatments experienced a reduction of 7.0 days and 5.4 days in the erenumab 140mg and 70mg, respectively, compared to placebo reduction of 2.7 days (p<0.001). In the erenumab treated arms, the odds of cutting migraine days in at least half was three-to-four fold higher than in the placebo arm (140mg: 41.3% , 70mg: 35.6%, placebo: 14.2% (p<0.001 for both doses versus placebo). The trial enrolled 667 patients (mean age 42.1, 79.0 percent female) who were randomised to receive either subcutaneous placebo (n=286) or subcutaneous erenumab 70 mg (n=191) or 140 mg (n=190) once a month [58] [85] [84] [82] [61] [62] [59] .

Interim data from a five-year open-label extension phase of the randomised, double-blind, placebo-controlled phase IIb 20120178 trial in 383 patients with episodic migraine demonstrated that more than one in four (26%) patients who were assessed over fifteen months, were completely migraine free. Sustained reduction with an average of 5.3 day from a baseline of 8.7 mean monthly migraine days was observed at week 52 with administration of erenumab 70mg monthly subcutaneous injection, regardless of treatment received during the blinded phase. At 52 weeks, there was 62% of 50% responder rate 38% of 75% responder rate and 19% of 100% responder rate. By the end of the study, patients who used (acute migraine-specific medication) AMSM to treat their migraine headaches experienced an average reduction in AMSM use of 4.4 days from the placebo controlled treatment period baseline of 6.2 days [35] [20] [53] [54] .

Updated results from open-label extension phase II trial, showed that after the long term treatment of erenumab conversion of chronic migraine to episodic migraine was observed. The conversion was 64% at week 12, 68% at week 24, 69% at week 40 and 72% at week 52. By end of the last dose, 69% and 76% were converted at week 52. Monthly migraine days for converters against non-converters was −10.6/−3.8 (70mg) and −12.5/−4.2 (140mg). Around greater than 50% patients showed the response for converters as 105/148 (70mg) and 103/125 (140mg) at week 52 and 50% and greater for non-converters response was 9/66 (70mg) and 8/40 (140mg) at week 52 [63] . Interim results of the open-label extension (OLE) 20130255 study in 609 patients with chronic migraine demonstrated sustained benefits up to one year with erenumab treatment. Patients taking erenumab 140 mg and 70 mg (based on last dose received) achieved reductions of average monthly migraine days of 10.5 and 8.5 days, respectively, when compared with a baseline of 18.1 days. Patients treated with erenumab experienced reductions in monthly migraine days of 50% or more (67% patients on 140 mg and 53% patients on 70 mg), 75% or more (42% on 140 mg and 27% on 70 mg) and 100% reduction (13% on 140 mg and 6% on 70 mg). Updated results from an exploratory analysis of the OLE showed that at 52 weeks, more than two-thirds of patients with chronic migraine converted to episodic migraine by the time they received the last dose of erenumab. The monthly migraine days (MMD) reduced from 17 at baseline, to 11 at week 52, for these patients. Both doses explored in the OLE displayed high conversion rates, with the 140mg dose of erenumab being numerically higher (76%), as compared with the 70mg dose (69%) [38] [52] [60] .

Phase I:

In a phase I trial involving 34 healthy adults, baseline mean (SD) systolic BP (SBP), diastolic BP (DBP), and MAP, respectively, were 122.8 (6.5), 70.1 (5.6), and 87.5 (5.0) mmHg. Differences in SBP, DBP, or MAP were not observed between subjects who received sumatriptan alone and those who received concomitant sumatriptan and erenumab (upper limit of the 90% CI for the treatment difference was <5 mmHg). A post-hoc analysis revealed no increase in MAP within the same subjects following erenumab alone (mean [SD] change from pre-dose: -0.3 [5.2]) or placebo (-0.5 [5.7]); but a mean change of 0.7 (4.8) was observed, following administration of sumatriptan alone [66] [67] .

Positive results of the randomised, placebo-controlled, six-month phase II trial in Japanese patients (n = 475) for the prevention of episodic migraine demonstrated that erenumab showed statistically significant differences for all primary and secondary endpoints, when compared with placebo. Patients taking erenumab at the dose of 70 mg and 140 mg observed a significant reduction in mean monthly migraine days (MMD) (differences from placebo in reduction of mean MMD are 2.3 and 1.9 day, individually, p < 0.001). Patients taking erenumab 70 mg and 140 mg doses were significantly achieved a 50% or greater reduction in MMD, than the patients treated with placebo. Acute migraine-specific medication treatment days were also significantly reduced in the patients taking erenumab. Erenumab treated patients reported significant improvements in HIT-6TM, a patient-reported outcome assessing the impact of migraine on their lives, when compared with placebo [57] [56] .

Phase II

The phase II Treadmill Cardiovascular safety trial met it primary endpoint of noninferiority, showing no difference in exercise time among participants receiving erenumab or placebo. As compared with placebo, the change from baseline in total exercise time was non-inferior in the erenumab group, while no differences were observed in the time to onset of 1mm ST-segment depression, time to onset of exercise-induced angina. The treatment difference in mean change from baseline in exercise time was -11.0 seconds (90 percent confidence interval -44.9, 22.9). In addition, no significant differences were seen between the two groups in time to onset of angina or time to onset of electrocardiogram change consistent with onset of myocardial ischaemia. The trial evaluated the effect of erenumab on exercise time during a treadmill test in 89 subjects with stable angina [86] [58] [73] .

In both phase II 20120309 and phase III 20170609 trial, erenumab significantly reduced monthly migraine days (MMD) from baseline over months 4, 5 and 6 of the double-blind treatment period (DBTP) [23] .

Results of a subgroup analysis from phase III STRIVE trial in women of childbearing potential with/without a self-reported history of MRM demonstrated a similar mean baseline MMDs. The least squares means (LSM, SE) of change in MMD for 70mg and 140mg vs placebo (p<0.001 for all) were ‒ 3.3 (0.4)/ ‒ 3.4 (0.3) and ‒ 3.6 (0.4)/ ‒ 3.6 (0.2) vs ‒ 1.5 (0.4)/ ‒ 1.9 (0.3). The change in the LSM (SE) in MSMD was‒ 1.1 (0.2)/ ‒ 1.1 (0.2) and ‒ 1.6 (0.2)/ ‒ 1.5 (0.2) vs ‒ 0.1 (0.2)/ ‒ 0.2 (0.2) for 70mg and 140mg vs placebo (p=0.002/<0.001 for 70mg, p<0.001/<0.001 for 140mg). For 70mg, a ≥ 50% reduction in MMD was achieved, 45%/42% (OR: 2.3/2.0; p=0.016/0.005), 50%/47% (OR: 2.7/2.6; p=0.002/<0.001) for 140mg, and 27%/27% for placebo. Eerenumab equally reduced MMD, MSMD and improved 50% responder rate in women with and without a history of menstrually-related migraine (MRM) [40] [77] .

Future Events

Expected Date Event Type Description Updated
31 Dec 2024 Regulatory Status Novartis intends to file first regulatory application in Migraine in or after 2024 [76] 28 Jul 2020
09 Sep 2019 Trial Update Amgen plans the phase III OASIS (CM) trial for Migraine (In adolescents, In children) in Belgium, Finland, Germany, Hungary, Poland, the United Kingdom and the USA in Septmeber 2019(EudraCT2017-002399-23) (NCT03832998) (700304411) 14 Jul 2020
02 Sep 2019 Trial Update Novartis plans the phase III DRAGON trial in Migraine in September 2019 (NCT03867201) (700305295) 11 Sep 2019
06 Jun 2019 Trial Update Amgen plans the phase III OASIS (EM) trial for Migraine (Prevention, In adolescents, In children) in Belgium, Canada, Colombia, England, Finland, Germany, Hungary, Poland, Russia, Scotland, Switzerland, United Kingdom, USA (SC) (EudraCT2017-002397-39) (NCT03836040) 31 Jul 2019
18 Apr 2019 Trial Update Amgen plans a phase III trial for Migraine (Prevention, In adults, In the elderly) in Japan in April 2019 (NCT03812224) (700303809) 10 Jul 2019
31 May 2018 Regulatory Status Amgen intends to launch erenumab for Migraine in May 2018 [11] 01 Aug 2018
17 May 2018 Regulatory Status FDA assigns PDUFA action date of 17/05/2018 for erenumab for Migraine (Prevention) [13] 21 May 2018
05 Feb 2018 Trial Update Novartis Pharmaceuticals plans the phase III EMPOwER trial in Migraine (Prevention) (SC) (CAMG334A2302; NCT03333109) (700290118) 01 Mar 2018

Development History

Event Date Update Type Comment
28 Jun 2021 Phase Change - No development reported No recent reports of development identified for phase-I development in Migraine(In adolescents, In children) in USA Updated 28 Jun 2021
23 Jun 2021 Phase Change - Registered Registered for Migraine (Prevention, In adults) in Japan (SC) [23] Updated 24 Jun 2021
23 Jun 2021 Scientific Update Pooled efficacy and safety data from phase II and phase III in Migraine released by Amgen [23] Updated 24 Jun 2021
17 Apr 2021 Scientific Update Updated efficacy and adverse events data from open-label extension study of phase II trial in migraine presented at the 73rd Annual Meeting of the American Academy of Neurology (AAN-2021) [55] Updated 23 Jun 2021
01 Feb 2021 Financial Update Credit Suisse financial data update Updated 14 Mar 2021
25 Nov 2020 Trial Update Amgen completes the phase III trial in Migraine (Prevention, In adults, In the elderly) in Japan (SC) (NCT03812224) Updated 09 Dec 2020
03 Oct 2020 Scientific Update Efficacy and safety data from a phase II trial in migraine released by Amgen [35] Updated 06 Oct 2020
01 Sep 2020 Phase Change - Preregistration Preregistration for Migraine (Prevention) in Japan (SC) [24] Updated 30 Oct 2020
22 Jul 2020 Regulatory Status Novartis intends to file first regulatory application in Migraine in or after 2024 [76] Updated 28 Jul 2020
09 Jun 2020 Phase Change - II Phase-II clinical trials in Rosacea in Denmark (SC) (NCT04419259) Updated 25 Jun 2020
25 Apr 2020 Scientific Update Long-term safety data from a phase II trial in Migraine presented at the 72nd Annual Meeting of the American Academy of Neurology (AAN-2020) [50] Updated 22 May 2020
04 Feb 2020 Regulatory Status An independent appeal panel pronounces that NICE needs to request evidence for establishing erenumab effectiveness in a subgroup of patients with Migraine [6] Updated 10 Feb 2020
13 Jan 2020 Trial Update Novartis completes the phase III EMPOwER trial in Migraine (Prevention) in Argentina, India, Mexico, Philippines, Vietnam, South Korea, Lebanon, Malaysia, Singapore, Taiwan and Thailand (SC) (NCT03333109) Updated 16 Apr 2020
31 Dec 2019 Trial Update Danish Headache Center in collaboration with Novartis and Amgen completes a phase II trial in Headache (Prevention) in Denmark (SC, Injection) (NCT03974360) Updated 19 Feb 2020
28 Oct 2019 Phase Change - II Phase-II clinical trials in Trigeminal neuralgia in Denmark (unspecified route) (NCT04054024) Updated 29 Nov 2019
09 Sep 2019 Scientific Update Long-term efficacy and safety data from a phase II trial in Migraine released by Novartis [51] Updated 10 Sep 2019
05 Sep 2019 Phase Change - III Phase-III clinical trials in Migraine (In adolescents, In children, Prevention) in Poland, Germany, Canada, Italy, Japan (SC) (EudraCT2017-002399-23) (NCT03832998) Updated 14 Jul 2020
05 Sep 2019 Trial Update Amgen initiates enrolment in the phase III OASIS trial for Migraine (In adolescents, In children, Prevention) in USA, Belgium, Finland, Hungary, United Kingdom (SC) (EudraCT2017-002399-23) (NCT03832998) Updated 14 Jul 2020
26 Aug 2019 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in China(NCT03867201) Updated 17 Aug 2021
16 Aug 2019 Trial Update Amgen plans the phase III OASIS (CM) trial for Migraine (In adolescents, In children) in Belgium, Finland, Germany, Hungary, Poland, the United Kingdom and the USA in Septmeber 2019(EudraCT2017-002399-23) (NCT03832998) Updated 14 Jul 2020
13 Aug 2019 Phase Change - Marketed Launched for Migraine (Prevention) in Spain (SC) Updated 10 Sep 2019
19 Jul 2019 Trial Update Amgen initiates enrolment in the phase III OASIS trial for Migraine (In adolescents, In children, Prevention) in Germany, Poland, Canada, Italy, Japan (SC) (EudraCT2017-002399-23) (NCT03832998) Updated 14 Jul 2020
19 Jul 2019 Phase Change - III Phase-III clinical trials in Migraine (In adolescents, In children, Prevention) in Finland, Belgium, USA, Hungary, Switzerland, United Kingdom (SC) (NCT03836040) (EudraCT2017-002397-39) Updated 31 Jul 2019
02 Jul 2019 Scientific Update Updated efficacy data from the phase III STRIVE trial in Migraine released by Novartis [37] Updated 03 Jul 2019
01 Jul 2019 Scientific Update Updated efficacy data from the phase IIIb LIBERTY trial in Migraine released by Novartis [30] Updated 05 Jul 2019
05 Jun 2019 Trial Update Amgen completes a phase II trial in Migraine (Prevention) in Japan (SC) (NCT02630459) Updated 10 Jul 2019
04 May 2019 Scientific Update Efficacy data from a open-extension study for phase II trial in Migraine presented at the 71th Annual Meeting of the American Academy of Neurology (AAN-2019) [63] Updated 21 Nov 2019
04 May 2019 Scientific Update Updated efficacy data from the phase III STRIVE trial in Migraine presented at the 71st Annual Meeting of the American Academy of Neurology (AAN-2019) [36] Updated 20 Nov 2019
04 May 2019 Scientific Update Efficacy data from the phase IIIb LIBERTY trial in Migraine presented at the 71st Annual Meeting of the American Academy of Neurology [29] Updated 01 Nov 2019
02 May 2019 Scientific Update Updated efficacy data from the phase III STRIVE trial and a one-year open label extension (OLE) trial in Migraine released by Amgen [38] Updated 07 May 2019
12 Apr 2019 Phase Change - III Phase-III clinical trials in Migraine (Prevention, In adults, In the elderly) in Japan (SC) (NCT03812224) Updated 02 May 2019
05 Apr 2019 Phase Change - II Phase-II clinical trials in Headache (Prevention) in Denmark (SC) (NCT03974360) Updated 12 Jun 2019
04 Apr 2019 Licensing Status Novartis files lawsuit against Amgen concerning the latter's Notice of termination of collaboration agreement [3] Updated 10 Apr 2019
31 Mar 2019 Phase Change - Registered Registered for Migraine (Prevention, In adults) in USA (SC) [4] Updated 06 May 2019
13 Mar 2019 Trial Update Novartis plans the phase III DRAGON trial in Migraine in September 2019 (NCT03867201) Updated 11 Sep 2019
23 Feb 2019 Trial Update Amgen plans the phase III OASIS (EM) trial for Migraine (Prevention, In adolescents, In children) in Belgium, Canada, Colombia, England, Finland, Germany, Hungary, Poland, Russia, Scotland, Switzerland, United Kingdom, USA (SC) (EudraCT2017-002397-39) (NCT03836040) Updated 31 Jul 2019
23 Jan 2019 Trial Update Amgen plans a phase III trial for Migraine (Prevention, In adults, In the elderly) in Japan in April 2019 (NCT03812224) Updated 10 Jul 2019
10 Jan 2019 Regulatory Status The National Institute for Health and Care Excellence (NICE) does not recommend erenumab for routine use on the National Health Services (NHS) for Migraine (Prevention, In adults) [8] Updated 16 Jan 2019
03 Dec 2018 Phase Change - Marketed Launched for Migraine (Prevention) in Canada (SC) [17] Updated 05 Dec 2018
19 Nov 2018 Scientific Update Interim efficacy and adverse events data from a phase II trial in migraine released by Amgen Astellas Biopharma [57] Updated 27 Nov 2018
29 Oct 2018 Phase Change - Registered Registered for Migraine (Prevention) in United Arab Emirates (SC), Singapore (SC) [9] Updated 29 Oct 2018
23 Oct 2018 Scientific Update Efficacy and adverse events data from the phase IIIb LIBERTY trial in Migraine released by Novartis [9] Updated 29 Oct 2018
30 Sep 2018 Phase Change - Marketed Launched for Migraine (Prevention) in Switzerland, Iceland, Liechtenstein, Norway, Norway, European Union (SC) [19] Updated 24 Oct 2018
07 Sep 2018 Trial Update Novartis completes enrolment in its phase III LIBERTY trial for Migraine (Prevention) in Australia, Austria, Belgium, Czech, Denmark, Finland, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, Switzerland and in the UK (NCT03096834) (EudraCT2016-002211-18) Updated 11 Jan 2021
03 Aug 2018 Phase Change - Registered Registered for Migraine (Prevention) in Canada (SC) [18] Updated 07 Aug 2018
30 Jul 2018 Scientific Update Updated efficacy data from a phase IIb trial in Episodic migraine released by Novartis [20] Updated 03 Aug 2018
30 Jul 2018 Phase Change - Registered Registered for Migraine (Prevention) in European Union, Iceland, Liechtenstein, Norway (SC) [20] Updated 01 Aug 2018
26 Jul 2018 Phase Change - Preregistration Preregistration for Migraine (Prevention, In adults) in USA (SC, Injection, 140 mg) [5] Updated 17 Aug 2018
18 Jul 2018 Phase Change - Marketed Launched for Migraine (Prevention, In adults) in USA (SC) [12] Updated 20 Jul 2018
13 Jul 2018 Phase Change - Registered Registered for Migraine (Prevention) in Switzerland (SC) [20] Updated 01 Aug 2018
03 Jul 2018 Phase Change - Registered Registered for Migraine (Prevention) in Australia (SC) [20] Updated 01 Aug 2018
28 Jun 2018 Scientific Update Interim three-year adverse events data from open-label extension of the phase IIb trial in Migraine released by Amgen [52] Updated 06 Jul 2018
28 Jun 2018 Scientific Update Interim efficacy and adverse events data from open-label extension of the phase II trial in Migraine released by Amgen [52] Updated 06 Jul 2018
01 Jun 2018 Regulatory Status The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recommends approval of erenumab for Migraine (Prevention) in European Union [22] Updated 04 Jun 2018
22 May 2018 Phase Change - Discontinued(I) Discontinued - Phase-I for Migraine in Belgium (IV) Updated 22 May 2018
21 May 2018 Phase Change - Discontinued(I) Discontinued - Phase-I for Hot flashes in USA (SC) Updated 21 May 2018
17 May 2018 Regulatory Status Amgen intends to launch erenumab for Migraine in May 2018 [11] Updated 01 Aug 2018
17 May 2018 Phase Change - Registered Registered for Migraine (Prevention, In adults) in USA (SC) - First global approval [10] Updated 21 May 2018
04 May 2018 Phase Change - I Phase-I clinical trials in Migraine (In adolescents, In children) in USA (unspecified route) (NCT03499119) Updated 13 Jun 2018
21 Apr 2018 Scientific Update Efficacy data from a phase III STRIVE trial in Migraine with aura and Menstrually-related migraine presented at the 70th Annual Meeting of the American Academy of Neurology (AAN-2018) [41] [77] Updated 10 May 2018
21 Apr 2018 Scientific Update Immunogenicity and safety data from pooled analysis of clinical trials in Migraine presented at the 70th Annual Meeting of the American Academy of Neurology (AAN-2018) [78] [79] Updated 10 May 2018
18 Apr 2018 Trial Update Amgen plans a phase I trial for Migraine (In Children and Adolescents) in USA (NCT03499119) Updated 19 Apr 2018
17 Apr 2018 Scientific Update Adverse events data from the phase III LIBERTY trial in Migraine released by Amgen [31] Updated 20 Apr 2018
17 Apr 2018 Scientific Update Updated efficacy data from the phase III LIBERTY trial in Migraine released by Amgen [80] Updated 20 Apr 2018
08 Feb 2018 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in Vietnam, Philippines, Mexico, India (SC) (NCT03333109) Updated 16 Apr 2020
08 Feb 2018 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in Thailand, Taiwan, Singapore, Malaysia, South Korea, Argentina (SC) (NCT03333109) Updated 21 May 2018
08 Feb 2018 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in Lebanon (SC) (NCT03333109) Updated 01 Mar 2018
24 Jan 2018 Patent Information Novartis has patent protection for Erenumab in USA and the European Union [75] Updated 20 Apr 2018
22 Jan 2018 Scientific Update Efficacy data from a phase III trial in Migraine released by Novartis [32] Updated 23 Jan 2018
29 Nov 2017 Scientific Update Efficacy data from the phase III STRIVE trial in Migraine (prevention) released by Amgen [42] Updated 01 Dec 2017
08 Nov 2017 Trial Update Amgen completes a phase I trial for Migraine (Prevention) in USA, Belgium and Netherlands (SC) (NCT02542605) Updated 21 Dec 2017
06 Nov 2017 Trial Update Novartis Pharmaceuticals plans the phase III EMPOwER trial in Migraine (Prevention) (SC) (CAMG334A2302; NCT03333109) Updated 01 Mar 2018
07 Sep 2017 Scientific Update Safety and efficacy data from the phase II Treadmill Cardiovascular safety trial released by Amgen [58] Updated 11 Sep 2017
07 Sep 2017 Scientific Update Updated efficacy data from a phase II trial in Migraine released by Amgen [58] Updated 11 Sep 2017
20 Jul 2017 Regulatory Status FDA assigns PDUFA action date of 17/05/2018 for erenumab for Migraine (Prevention) [13] Updated 21 May 2018
20 Jul 2017 Regulatory Status The US FDA accepts BLA for erenumab for Migraine for review [13] Updated 21 Jul 2017
21 Jun 2017 Regulatory Status The European Medicines Agency (EMA) accepts marketing authorisation application (MAA) for erenumab for Migraine for review [14] Updated 25 Jun 2017
19 Jun 2017 Trial Update Amgen completes the phase III STRIVE trial in Migraine (Prevention) in USA, Austria, Belgium, Canada, Czech Republic, Finland, Germany, Hungary, Netherlands, Sweden, Slovakia, Poland, Turkey and United Kingdom(NCT02456740) Updated 04 Jul 2017
31 May 2017 Phase Change - Preregistration Preregistration for Migraine (Prevention) in European Union (SC) [15] Updated 19 Jun 2017
26 May 2017 Trial Update Amgen completes an open-label extension phase II trial for Migraine (Prevention) in USA, Canada, Czech Republic, Denmark, Finland, Germany, Norway, Poland, Sweden, United Kingdom (SC) (NCT02174861) Updated 12 Jun 2017
18 May 2017 Phase Change - Preregistration Preregistration for Migraine (Prevention) in USA (SC) [16] Updated 24 May 2017
24 Apr 2017 Licensing Status Amgen and Novartis agree to co-promote erenumab in USA [2] Updated 02 May 2017
22 Apr 2017 Scientific Update Efficacy data from a phase I trial in Healthy volunteers presented at the 69th Annual Meeting of the American Academy of Neurology (AAN-2017) [66] Updated 13 Jun 2017
13 Apr 2017 Trial Update Amgen completes a phase II cardiovascular safety trial in USA, Slovakia, Bulgaria, Germany, Latvia, Czech Republic, Poland, New Zealand, Romania, South Africa and Switzerland (IV) (NCT02575833) Updated 25 May 2017
20 Mar 2017 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in Australia (SC) (NCT03096834) Updated 23 Jan 2018
20 Mar 2017 Trial Update Novartis initiates enrolment in the LIBERTY trial for Migraine (Prevention) in France, Italy, Norway and Switzerland after March 2017 (NCT03096834) Updated 23 Jan 2018
20 Mar 2017 Trial Update Amgen completes a phase III trial in Migraine (Prevention) in USA, Denmark, France, Greece, Portugal, Russia, Switzerland (NCT02483585) Updated 03 Apr 2017
16 Nov 2016 Scientific Update Safety and efficacy data from the phase III STRIVE trial in Migraine (Prevention) released by Amgen [39] Updated 22 Nov 2016
16 Nov 2016 Trial Update Amgen completes enrolment in the phase III STRIVE clinical trials in Migraine (Prevention) in Czech Republic, United Kingdom, Turkey, Slovakia, Netherlands, Belgium, Poland, Canada, USA, Austria, Finland, Germany, Sweden, Hungary before November 2016 (NCT02456740) Updated 22 Nov 2016
31 Oct 2016 Trial Update Novartis initiates enrolment in the phase III LIBERTY trial in Migraine (Prevention) in United Kingdom, Sweden, Germany, Greece and the Netherlands (EudraCT2016-002211-18) Updated 03 Apr 2017
31 Oct 2016 Trial Update Novartis initiates enrolment in the phase III LIBERTY trial in Migraine (Prevention) in Czech Republic, Finland, and Denmark (EudraCT2016-002211-18) Updated 22 Nov 2016
22 Oct 2016 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in Spain (SC) (EudraCT2016-002211-18) Updated 27 Oct 2016
20 Oct 2016 Trial Update Novartis Pharma initiates the phase III LIBERTY trial for Migraine (Prevention) in Austria (SC) (EudraCT2016-002211-18) Updated 26 Oct 2016
28 Sep 2016 Scientific Update Efficacy and safety data from the ARISE (Phase III) trial in Migraine released by Amgen [44] Updated 03 Oct 2016
15 Sep 2016 Scientific Update Efficacy and adverse events data from a phase II trial in Migraine (Prevention) released by Amgen [61] Updated 19 Sep 2016
01 Sep 2016 Trial Update Amgen completes a phase I drug-drug interaction trial in Healthy female volunteers in USA (unspecified) (NCT02792517) Updated 18 Oct 2016
01 Aug 2016 Trial Update Amgen completes a phase I trial in Healthy volunteers in Belgium (NCT02741310) Updated 26 Sep 2016
16 Jul 2016 Phase Change - No development reported No recent reports of development identified for phase-I development in Hot-flashes in USA (SC, Injection) Updated 16 Jul 2016
16 Jul 2016 Phase Change - No development reported No recent reports of development identified for phase-I development in Migraine in Belgium (IV) Updated 16 Jul 2016
16 Jul 2016 Phase Change - No development reported No recent reports of development identified for phase-I development in Migraine in Belgium (SC, Injection) Updated 16 Jul 2016
08 Jun 2016 Scientific Update Efficacy and adverse events data from a phase II trial in Migraine (Prevention) released by Amgen [62] Updated 13 Jun 2016
30 Apr 2016 Trial Update Amgen completes a phase II trial for Migraine (Prevention) in USA, Canada, Denmark, Finland, Germany, Norway and Sweden (NCT02066415, EudraCT2013-001707-36) Updated 06 Jun 2016
01 Feb 2016 Trial Update Amgen initiates a phase I drug-drug interaction trial in Healthy female volunteers in USA (unspecified) (NCT02792517) Updated 09 Jun 2016
01 Feb 2016 Trial Update Amgen initiates enrolment in a phase I trial in Healthy volunteers in Belgium (NCT02741310) Updated 20 Apr 2016
01 Jan 2016 Phase Change - II Phase-II clinical trials in Migraine (Prevention) in Japan (SC) (NCT02630459) Updated 18 Dec 2015
23 Nov 2015 Trial Update Amgen initiates a phase II cardiovascular safety trial in USA, Slovakia, Bulgaria, Germany, Latvia, Czech Republic, Poland, New Zealand, Romania, South Africa and Switzerland (IV) (EudraCT2015-002322-40) (NCT02575833) Updated 15 Sep 2017
11 Nov 2015 Trial Update Amgen initiates enrolment in a phase I trial for Migraine (Prevention) in Belgium and Netherlands(SC) (NCT02542605) Updated 21 Dec 2017
01 Nov 2015 Trial Update Amgen initiates a phase I trial for Migraine (Prevention) in USA (SC) (NCT02542605) Updated 03 Dec 2015
14 Oct 2015 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in Denmark (SC) Updated 19 Oct 2015
07 Oct 2015 Trial Update Amgen plans a phase II cardiovascular safety trial in USA (NCT02575833) Updated 26 Oct 2015
07 Oct 2015 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in Sweden (SC) Updated 19 Oct 2015
10 Sep 2015 Trial Update Amgen plans to initiate a phase I trial for Migraine (Prevention) in USA (NCT02542605) Updated 10 Sep 2015
01 Sep 2015 Licensing Status AMG 301 licensed to Novartis worldwide excluding, USA, Canada and Japan [1] Updated 07 Sep 2015
20 Jul 2015 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in France, Greece, Portugal, Russia, Switzerland (SC) (NCT02483585) Updated 03 Apr 2017
20 Jul 2015 Trial Update Amgen initiates a phase III trial in Migraine (Prevention) in Spain (NCT02483585) Updated 03 Apr 2017
02 Jul 2015 Trial Update Amgen plans the phase III ARISE trial in Migraine in USA, Denmark, Spain, Portugal, Russia, France, Greece, Switzerland and Mexico (NCT02483585) Updated 02 Jul 2015
01 Jul 2015 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in Czech Republic, United Kingdom, Turkey, Slovakia, Netherlands, Belgium (SC) after July 2015 (NCT02456740) Updated 22 Nov 2016
01 Jul 2015 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in Poland, Canada, USA (SC) after July 2015 (NCT02456740) Updated 10 Sep 2015
01 Jul 2015 Trial Update Amgen initiates enrolment in a phase III trial for Migraine (Prevention) in USA (NCT02483585) Updated 10 Sep 2015
25 Jun 2015 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in Germany, Austria and Hungary (SC) Updated 19 Oct 2015
25 Jun 2015 Phase Change - III Phase-III clinical trials in Migraine (Prevention) in Finland (SC) (EudraCT2014-004464-38) Updated 02 Jul 2015
19 Jun 2015 Scientific Update Interim efficacy and adverse events data from a phase II long-term extension trial in Migraine (Prevention) released by Amgen [53] Updated 04 Jul 2015
15 May 2015 Scientific Update Efficacy and adverse events data from a phase II trial in Migraine (Prevention) released by Amgen [49] Updated 30 May 2015
27 Jan 2015 Trial Update Amgen completes a phase II trial in Migraine (Prevention) in USA, Canada, Denmark, Finland, Germany, Norway and Sweden [48] (NCT01952574) Updated 02 Feb 2015
01 Oct 2014 Trial Update Amgen completes a phase I trial in Hot flashes in USA (SC) (NCT01890109) Updated 02 Dec 2014
01 Jul 2014 Trial Update Amgen completes a phase I trial in Migraine in Belgium (NCT01723514) Updated 05 Sep 2014
30 Jun 2014 Trial Update Amgen initiates enrolment in a phase II trial for Migraine (Prevention) in USA, Canada, Czech Republic, Denmark, Finland, Germany, Norway, Poland, Sweden, United Kingdom (SC) (NCT02174861) Updated 04 Jul 2015
28 May 2014 Trial Update Amgen initiates enrolment in a phase II trial for Migraine (prevention) in Denmark (EudraCT2013-005311-27) Updated 22 Jul 2014
26 Feb 2014 Trial Update Amgen initiates enrolment in a phase II trial for Migraine (prevention) in Germany and Norway (EudraCT2013-001707-36) Updated 06 Jun 2014
17 Feb 2014 Trial Update Amgen plans a phase II trial for Migraine (prevention) in the US, Canada and the EU (NCT02066415) Updated 27 Feb 2014
01 Feb 2014 Phase Change - II Phase-II clinical trials in Migraine (Prevention) in Poland and Czech Republic (SC) Updated 02 Feb 2015
01 Feb 2014 Trial Update Amgen initiates enrolment in a phase II trial for Migraine (Prevention) in USA, Canada, Denmark, Finland, Germany, Norway and Sweden (NCT02066415, EudraCT2013-001707-36) Updated 02 Feb 2015
25 Nov 2013 Trial Update Amgen terminates phase I trial in Migraine in Belgium (NCT01688739) Updated 03 Dec 2013
01 Aug 2013 Phase Change - II Phase-II clinical trials in Migraine (Prevention) in Canada (SC) Updated 02 Feb 2015
01 Aug 2013 Phase Change - II Phase-II clinical trials in Migraine (Prevention) in USA (SC) Updated 02 Feb 2015
01 Aug 2013 Phase Change - II Phase-II clinical trials in Migraine (prevention) in Denmark (SC) after August 2013 Updated 06 Jun 2014
01 Aug 2013 Phase Change - II Phase-II clinical trials in Migraine (prevention) in Germany, Norway and Sweden (SC) after August 2013 Updated 27 Feb 2014
01 Aug 2013 Phase Change - II Phase-II clinical trials in Migraine (prevention) in Finland (SC) Updated 23 Jul 2013
01 May 2013 Phase Change - I Phase-I clinical trials in Hot flashes in USA (SC) (NCT01890109) Updated 16 Jul 2013
30 Nov 2012 Trial Update Amgen initiates enrolment in a phase I trial for Migraine in Belgium (NCT01723514) Updated 22 Jan 2013
07 Nov 2012 Trial Update Amgen plans a phase I trial for Migraine in Belgium (NCT01723514) Updated 04 Dec 2012
31 Mar 2012 Phase Change - I Phase-I clinical trials in Migraine in Belgium (IV) Updated 04 Dec 2012
31 Mar 2012 Phase Change - I Phase-I clinical trials in Migraine in Belgium (SC) Updated 04 Dec 2012

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  83. Amgen Reports First Quarter 2018 Financial Results.

    Media Release
  84. Tepper S, Widnell K, Dolezil D, Ashina M, Reuter U, Brandes JL, et al. Evaluating the Efficacy and Safety of Erenumab (AMG 334) In Chronic Migraine Prevention in a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study. AAN-2017 2017; abstr. 1200.

    Available from: URL: http://submissions.mirasmart.com/AAN2017/itinerary/login.asp
  85. Amgen Presents Erenumab Data At The 59th Annual Scientific Meeting of the American Headache Society.

    Media Release
  86. Emerging Migraine Therapies Show Promise in Basic and Clinical Highlights Presented at 18th Congress of the International Headache Society Sept. 7-10.

    Media Release
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