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   .
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by the British Association for the Study of Headache and the Association of British Neurologists against the final draft guidance (FAD) for erenumab, which did not recommend the drug, within its marketing authorisation, for prevention of migraine in adults who had a minimum of four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    .
In October 2018, Novartis announced that erenumab was approved for migraine in Singapore and the United Arab Emirates  .
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]   . 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      .
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  . In August 2018, erenumab (Aimovig®) was approved by Health Canada  .
In third quarter of 2018, Novartis launched erenumab for the prevention of migraine in adults in Europe  . 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)     .
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   .
In June 2021, pooled data from phase II (20120309) and phase III (20170609) trial [see below], released by Amgen 
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  .
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  .
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  . As of June 2021, patients treated with erenumab saw a reduction from baseline in their monthly migraine days  .
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  .
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)        . In October 2020, Amgen announced two-year data of phase III trial that showed sustained efficacy and no increases in adverse events rates  .
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        .
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  . 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   .
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  .
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  .
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   . 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)       . In October 2020, Amgen announced five-year data of phase II trial  . 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)  .
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  . 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  .
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   . 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   . 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   . 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  . In May 2019, Amgen presented the efficacy data at the 71th Annual Meeting of the American Academy of Neurology (AAN-2019)  .
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  .
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  .
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   .
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  .
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  .
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  .
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  .
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  .
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   .
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  .