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Aimovig™ (erenumab) is an injectable human monoclonal antibody (mAb) co-developed by pharmaceutical companies Novartis and Amgen.
Formerly known as AMG 334, Aimovig belongs to a class of drugs known as selective calcitonin gene-related peptide (CGRP) antagonists, used for the treatment of acute migraine attacks.
The US Food and Drug Administration (FDA) accepted the drug’s biological licence application (BLA) in July 2017 and the drug was approved in May 2018.
Novartis’ marketing authorisation (MA) application was accepted for review by the European Medicines Agency (EMA) in June 2017. Aimovig™ received approval from the European Commission (EC) in July 2018 for the prevention of migraine in adults.
The drug was also registered on the Australian Register of Therapeutic Goods (ARTG) in August 2018 and was approved by Switzerland’s Swissmedic in July 2018.
These regulatory applications were submitted following completion of the pivotal Phase III STRIVE study.
In April 2019, the Scottish Medicines Consortium accepted the use of Aimovig™ to treat chronic migraine patients whose prior treatment with at least three other preventive medicines has failed.
The UK’s National Institute for Health and Care Excellence (NICE), which reviews cost-effectiveness of a drug for use on the National Health Service (NHS),, however, declined to recommend the drug in September 2019 saying it’s not cost-effective. The drug is priced at approximately £5,000 a year per patient in the UK.
Aimovig development background
Novartis and Amgen partnered in August 2015 to commercialise and develop neuroscience treatments for Alzheimer’s Disease (AD) and migraine. The collaboration focused on a number of Amgen’s drugs, including AMG 334 and AMG 301.
The agreement was expanded to include the co-commercialisation of Aimovig™ in the US in April 2017. Aimovig’s commercialisation rights in the US, Canada and Japan are owned by Amgen, while Novartis holds rights in the rest of the world.
In April 2019, Novartis filed a lawsuit against Amgen for allegedly trying to terminate their collaboration agreements related to Aimovig citing breach of material terms as the reason for termination.
Migraine causes and symptoms
Migraine is a neurological disorder characterised by the expansion of blood vessels in the brain due to the release of inflammatory substances from nerves. This results in severe headaches with symptoms, including nausea, vomiting and sensitivity to light or sound.
The root cause of migraine is unknown but the disorder is believed to occur as a result of a temporary change in the brain chemicals and blood vessels. It may also be caused by hormonal, emotional, physical, dietary and environmental changes, as well as certain other medical factors.
Aimovig’s mechanism of action
Aimovig™ blocks the CGRP receptor by inducing a CGRP receptor complex with a CGRP protein to emit migraine-associated pain signals. CGRP levels rise during migraine pain and subside to normal when pain reduces.
Aimovig™ is one of the first fully human mAbs approved for the treatment of migraine. It can be self-administered using a SureClick® autoinjector pen every four weeks.
Details of Phase II clinical study on Aimovig
A Phase II trial designated 20120295 was conducted on 667 patients, which were randomised in a 3:2:2 ratio to receive either 70mg or 140mg of Aimovig™ or placebo.
The randomised, 12-week, double-blind, placebo-controlled study achieved the primary endpoint of minimising the number of migraine days a month in comparison with placebo in both the dosage groups of Aimovig.
The results of the study demonstrated that patient groups of both doses witnessed a mean 6.6-day reduction from an average baseline of 18 migraine days a month, compared to 4.2 days observed in the placebo group.
The drug showed a 50% reduction in the number of days acute migraine-specific medication was used, as well as the cumulative hours of headaches, safety and tolerability.
Phase III trials on Aimovig drug
A multi-centre, randomised 24-week, double-blind, placebo-controlled Phase III study named STRIVE was conducted on 955 patients. They were administered either placebo or subcutaneous Aimovig™ in 70mg or 140mg doses in a 1:1:1 ratio once a month for six months.
The results of the study showed that patients that received higher doses witnessed a 3.7-day reduction in monthly migraine days from the baseline of 8.3 days. It also showed a reduction in the migraine days by half in 50% of the patients that consumed 140mg of Aimovig™, compared with placebo.
With an average baseline of 8.3 migraine days a month, the patients experienced between four and 14 migraine days a month. In the study’s double-blind treatment phase, the patients witnessed a primary endpoint change in the average migraine days each month over the preceding three months.
A Migraine Physical Function Impact Diary (MPFID) assessed the impact of migraines on physical function and everyday activities as secondary endpoints.
The FDA’s approval for Aimovig™ was based on results obtained from a Phase IIIb clinical study known as LIBERTY. It was a multi-centre, double-blind, placebo-controlled study that enrolled 246 patients with episodic migraine who had between two and four unsuccessful treatments. The patients were randomised to receive either 140mg Aimovig™ or placebo for 12-weeks.
The primary endpoint of the study was the percentage of patients with at least a 50% reduction of monthly migraine days from baseline over the last four weeks of the study.
The most common adverse reactions found in patients treated with Aimovig™ were injection site reactions and constipation.
Patients treated with Aimovig showed significant reductions in the number of migraine days each month during the extensive clinical programme that involved the participation of 2,600 patients. The safety and tolerability profile of the drug was found to be similar to placebo.
The five-year study assessed 70mg and 140mg doses of the drug, which decreased monthly migraine days and also cut the number of days on which medication for acute migraine is needed.
Data for 4.5 years from a long-term open-label treatment period (OLTP) showed that that treatment with the drug resulted in a 50% reduction in monthly migraine days in 77% of the patients that continued treatment, while 33% patients achieved full reduction.
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