New oral migraine prevention drug approved by FDA
Continuing the wave of cutting-edge new migraine drugs reaching the American market, the U.S. Food and Drug Administration (FDA) has now approved the first oral calcitonin gene-related peptide (CGRP) antagonist for acute migraine treatment.
The FDA approved the first CGRP antagonist for migraine treatment in early 2018. The landmark approval introduced the US market to an entirely new class of drug, developed to block key CGRP receptors in the brain known to play a major role in the onset of a migraine. Since then, several other CGRP antagonists have been approved, however, the first wave of these drugs was expensive and required administration by injection.
Now, the FDA has approved the first oral CGRP antagonist, designed to be taken as a migraine attack begins. Called Ubrelvy (ubrogepant), the new oral migraine drug has been in a race to market against its main competitor, rimegepant, a rival oral CGRP antagonist.
It is fair to say Ulbrevy’s Phase 3 clinical trial results have not been extraordinary. The trials generally did report statistically significant results, but questions have been raised over how clinically meaningful these results actually are. The primary measure of efficacy, pain freedom from migraine within two hours of dose, rarely reached much higher than 20 percent of the cohort, compared to placebo results between 11 and 14 percent.
A secondary measure, defined as “freedom from the most bothersome migraine-associated symptom at two hours” was only mildly better, demonstrating nearly 40 percent efficacy in the cohort. Although with the placebo group reporting nearly 30 percent efficacy, questions surrounding clinical significance can again be raised.
Looking at these results, and the initial Phase 3 data from rimegepant, the other oral CGRP antagonist racing to market, two neurologists last year published an article in the journal Headache suggesting this new class of drug, called gepants, to be akin to the emperor's new clothes.
“Are the effects of ubrogepant and rimegepant clinically relevant? They appear to have far lower efficacy than the triptans, and are not more effective than simple analgesics that can be purchased without a prescription,” the duo wrote. “Their purported safety or tolerability advantages over triptans are speculative and likely to be relevant for only a small proportion of migraineurs. We therefore find it justified to suggest that it is very difficult to see the Emperor’s new gepants.”
Rimegepant is on track for FDA approval in early 2020. It has reported relatively similar efficacy results to Ulbrevy.
Tens of millions of Americans suffer from migraines every year, and analysts are suggesting the market for these new oral CGRP drugs will be in the billions. Despite the questions over broader efficacy, the FDA believes these new drugs will help a large number of patients who otherwise have little current treatment options available.
“Ubrelvy represents an important new option for the acute treatment of migraine in adults, as it is the first drug in its class approved for this indication,” says Billy Dunn, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “The FDA is pleased to approve a novel treatment for patients suffering from migraine and will continue to work with stakeholders to promote the development of new safe and effective migraine therapies.”