- A migraine treatment developed by Washington-based Alder Biopharmaceuticals appeared to deliver less of a benefit over placebo than rival drugs, sending shares in the biotech down more than 20% in early Tuesday trading even though the Phase 3 study met its goal.
- Treatment with a 300 mg dose of Alder's drug, a CGRP inhibitor called eptinezumab, significantly reduced the number of monthly migraine days from baseline by 4.3 days over a three-month period. Patients studied in PROMISE-1 had frequent episodic migraine, defined as 14 headache days or less per month.
- But a high placebo response of 3.2 days translated to a placebo-adjusted lowering of 1.1 days, less than the near 2-day reductions seen in studies testing similar drugs from Eli Lilly & Co. and the team of Amgen and Novartis.
It's not often that a Phase 3 study succeeding on both primary and secondary endpoints cuts a biotech's stock price by a fifth.
Alder's eptinezumab, however, belongs to a closely watched class of drugs known as calcitonin gene-related peptide inhibitors that look set to bring a degree of relief to people suffering from chronic or episodic migraines.
Most existing options for migraine prevention were originally designed for other uses (Botox, for example), while other treatments do little to mitigate the underlying triggers which lead to episodic or chronic migraines. Yet, side effects and toxicity lead to discontinuation of treatment for many patients.
Due to the large potential market opportunity in the U.S., markets have been carefully following a quarter of monoclonal antibodies designed to target and block the CGRP pathway.
Phase 3 results for drugs from the team of Amgen and Novartis, and separately from Eli Lilly and Teva have read out over the past several quarters, setting the bar for Alder to keep up.
In PROMISE-1, the first of two pivotal Phase 3 studies, Alder tested 300 mg and 100 mg doses of eptinezumab. Both delivered a statistically significant reduction in the number of monthly migraine days over placebo, although the 300 mg dose led to better results.
Notably, roughly 30% of patients taking the 300 mg dose experienced at least a 75% reduction in the number of monthly migraine days over the three-month period, compared to only 16.2% for placebo. Over the entire six months of study, an average of one in five patients saw 100% responses with no migraines in any given month, Alder said.
Results from these so-called 'super-responders' could help Alder stay competitive with its big pharma rivals, even if its placebo-adjusted reduction across the entire study check in a notch lower.
Eli Lilly's galcanezumab led to a 38% proportion of patients experiencing a 75% reduction or more in its EVOLVE-1 study, and a 33% to 34% share in the EVOLVE-2 partner trial.
Also in Alder's benefit was eptinezumab's rapid onset of prevention. At the 300 mg dosing, Alder reported a nearly 54% reduction in the proportion of patients experiencing migraine on the day following administration, versus only 21% for placebo.
For patients with higher migraine frequency, rapid onset of effect would translate to more immediate relief — an issue with current treatment options that can take time to show any benefit.
Alder continues to enroll patients into its PROMISE-2 study, which focuses on chronic migraine, and plans to file an application for approval of eptinezumab with the Food and Drug Administration in the second half of 2018.
That would likely put Alder fourth to market, if all goes according to plan among its rivals. Amgen has already submitted a Biologics License Application to the FDA for erenumab, while both Lilly and Teva plan to file a submission later this year.
Both Lilly's galcanezumab and Amgen/Novartis' erenumab are designed for once-monthly subcutaneous dosing. Teva and Alder are aiming for a less-frequent and more convenient quarterly dosing, although Alder's drug is administered intravenously, while Teva's is subcutaneous.