The FDA has accepted for review the Biologics License Application (BLA) of Amgen and Novartis for the migraine prevention treatment Aimovig™ (erenumab).
Aimovig, also known as AMG 334, is indicated for the prevention of migraine in patients experiencing four or more migraine days per month. If approved, Aimovig would be the first-and-only monoclonal antibody specifically designed for the prevention of migraine, Amgen and Novartis said yesterday.
Aimovig is designed to inhibit the calcitonin gene-related peptide (CGRP) receptor, which is believed to play a causal role in migraine pathophysiology.
The BLA submitted for Aimovig includes data from pivotal studies of more than 2600 patients experiencing four or more days of migraine per month. In Phase II and Phase III clinical studies comparing the drug to placebo, Aimovig showed a reduction in the number of migraine-affected days, disability, and acute medication use for patients with episodic and chronic migraine.
In September 2016, Novartis trumpeted positive topline results from the 577-patient Phase III ARISE trial (NCT02483585). Aimovig patients showed a statistically significant 2.9-day reduction from baseline in monthly migraine days, compared to a 1.8-day reduction in patients randomized to placebo. At baseline, patients experienced between four and 14 migraine days each month, with an average of eight migraine days per month.
Two months later in November 2016, Amgen announced successful topline results from the 955-patient Phase III STRIVE trial (NCT02456740), in which Aimovig showed statistically significant reductions from baseline in monthly migraine days. Episodic migraine patients in the erenumab 70-mg and 140-mg treatment arms experienced reductions of 3.2 and 3.7 days from baseline in monthly migraine days, respectively, compared to a 1.8-day reduction in the placebo arm.
The safety profile of Aimovig was similar to placebo across all treatment arms in the Phase II and Phase III studies for up to six months. The most common adverse events across the studies were upper respiratory tract infection, injection site pain, nausea, and nasopharyngitis, Amgen said.
The FDA has set a May 18 target date for action under the Prescription Drug User Fee Act (PDUFA).
“We look forward to continuing our longstanding history of redefining clinical practice in neurology by working with the FDA to bring erenumab to people suffering from migraine, and to subsequently reduce the overall burden of this debilitating disease,” Vas Narasimhan, M.D., Novartis’ global head, drug development and CMO, said in a statement.
Added Sean E. Harper, M.D., evp of R&D at Amgen. “We are pleased to advance Aimovig, our migraine-specific preventive therapy, to help address the unmet need in this community and potentially mitigate the overall burden of this disease for patients who have already tried other therapeutic options.”
Teva, Lilly Candidates Also Shine in Trials
With Aimovig, Amgen and Novartis are competing against drug developers that include Teva Pharmaceutical Industries, whose migraine candidate fremanezumab (TEV-48125) generated positive results last month in the more than 2000-patient Phase III HALO trial.
Fremanezumab administered monthly improved the average number of migraine days, relative to baseline, by 41.6% for the duration of the trial (–3.7 days vs. –2.2 days for placebo). Participants had a mean of 9.1 migraine days per month and reported 39 days with functional impairment per quarter.
Also generating positive Phase III results has been Eli Lilly’s migraine candidate galcanezumab. In May, Lilly reported that galcanezumab succeeded in the EVOLVE-1, EVOLVE-2, and REGAIN trials:
- EVOLVE-1: Average reduction of 4.7 days for 120 mg and 4.6 days for 240 mg compared to an average reduction of 2.8 days for placebo.
- EVOLVE-2: Average reduction of 4.3 days for 120 mg and 4.2 days for 240 mg compared to an average reduction of 2.3 days for placebo.
- REGAIN: Average reduction of 4.8 days for 120 mg and 4.6 days for 240 mg compared to an average reduction of 2.7 days for placebo.
Amgen and Novartis are co-commercializing Aimovig in the U.S. under a collaboration agreement launched in September 2015 and originally envisioned as involving joint development and commercialization of treatments in Alzheimer's disease as well as migraine.
The companies amended their collaboration agreement in April. Amgen agreed to join Novartis in commercializing Aimovig, while Novartis agreed to exclusively promote the migraine prevention drug in Canada.
Several components of the original deal between the companies remain in effect. Amgen retained exclusive commercialization rights in Japan, while Novartis kept its commercialization rights in the rest of the world. Both companies also continue to collaborate on global co-development of Aimovig.