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Lilly, Teva Meet Endpoints for Cluster Headache & Migraine; Amgen/Novartis Gain FDA Approval of Aimovig

May 17, 2018
Anticipation over CGRPs continues as first medication in the class gains approval and others are on track to do the same

Amgen/Novartis have been awaiting an FDA decision on their collaborative erenumab (Aimovig), a calcitonin gene-related peptide (CGRP) monoclonal antibody for the prevention of migraine since they submitted a BLA for the novel treatment last July. Announced late in the day on May 17, 2018, FDA has granted approval to Amgen Inc. for Aimovig, making the once-monthly self-administered injection the first US FDA-approved preventive migraine treatment in the CGRP class.  

According to an FDA release, the monoclonal antibody was evaluated in three clinical trials that demonstrated effectiveness for those with episodic and chronic migraine compared to placebo. In the first trial (n=955), which included those with a history of episodic migraine, participants experienced, on average, one to two fewer migraine days per month. In the second (n=577) and third (n=667) studies, in which patients had a history of chronic migraine,  subjects experienced one fewer migraine day and 2-1/2 fewer migraine days, per month on average, respectively. Most commonly reported side effects were injection site reactions and constipation. (Read more from Amgen/Novartis representatives)

Amgen codeveloped Aimovig with Novartis, and is one of four companies pursuing regulatory approval of CGRP inhibitors for the prevention of migraine. Read the back story.

Lilly's Galcanezumab

Earlier in the week, Eli Lilly and Company (Indianapolis) announced that its CGRP monoclonal antibody, galcanezumab, met its primary endpoint in a Phase 3 study of patients with episodic cluster headache, which represents 85 to 90 percent of cluster headache cases, according to a company release. The large molecule demonstrated statistically significant differences in the reduction of weekly cluster headache attacks compared to placebo across Weeks 1 to 3 of the 2-month, double-blind treatment period. 

“A statistically significantly greater percentage of patients treated with galcanezumab also achieved at least a 50%reduction in weekly cluster headache attacks compared to placebo at Week 3, the gated secondary endpoint,” according to the release. Results align with previously observed safety and tolerability tests for the prevention of migraine.

The company also conducted a separate Phase 3 study for patients with chronic cluster headache, which represents 10 to 15%of cluster headache cases. This study did not meet its primary endpoint.

"Cluster headache can be difficult to evaluate in clinical studies, which has contributed to few available treatment options for cluster headache, often considered the most severe pain one can experience," noted Christi Shaw, president of Lilly Bio-Medicines, in the release.

Lilly’s combined studies evaluated more than 340 patients, representing the largest controlled preventive trials conducted in cluster headache to date. The company stated that it is working with regulatory agencies around the world to determine the best path forward. FDA is currently reviewing galcanezumab for the prevention of migraine in adults, with a decision expected in Q3 of this year (2018). 

Teva's Fremanezumab

On the same day as Lilly, Teva Pharmaceuticals (Jerusalem) announced the publication of its Phase 3 data for fremanezumab, a CGRP mAb expected to be indicated for episodic migraine.

The company’s Phase III HALO study evaluating the efficacy, safety, and tolerability of both quarterly and monthly subcutaneous dosing regimens of fremanezumab, compared to placebo, for the prevention of episodic migraine were released online by JAMA.  The multicenter, randomized, double-blind, placebo-controlled, parallel group trial (n = 875) met its primary endpoint demonstrating that fremanezumab significantly reduced monthly migraine days for both dosing regimens. Specifically, during the 12-week period after the first dose, monthly migraine days were significantly reduced to 4.9 days for monthly (p < 0.001) and 5.3 days for quarterly (p < 0.001) dosing compared with 6.5 days for placebo, according to the company’s release.

In addition, participants reporting ≥ 50% reduction in the monthly average number of migraine days achieved significantly greater results in monthly (47.7%, P < 0.001) and quarterly (44.4%, P < 0.001) dosing compared with placebo (27.9%). Fremanezumab significantly reduced monthly days of any acute headache medication use as well, to 4.4 days for monthly (P < 0.001) and 4.6 days for quarterly (P < 0.001) dosing compared with 5.8 days for placebo.

Results were observed through a screening visit, a 28-day pre-treatment period, a 12-week treatment period, and a final evaluation at Week 12. The most commonly reported adverse events included injection site pain, induration, and erythema. The Teva CGRP antibody is currently under FDA review for preventive migraine in adults. 

Coming in June: Practical Pain Management's cover story addresses the new CGRP migraine-inhibitor class, featuring perspectives from Amgen, Novartis, Lilly, Teva, Allergan and more!

Last updated on: June 16, 2020
Continue Reading:
Amgen/Novartis Move Successful Endpoint Results of Erenumab to First Migraine Preventive Approval in US
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