Biohaven Pharmaceuticals has become the latest to head to the FDA seeking approval of a new type of migraine drug. But it’s unclear whether the treatment, rimegepant, will stand out amidst a crowd of new medicines aiming to help people fend off the debilitating headaches after they start.
Biohaven (NYSE: [[ticker:BHVN]]), of New Haven, CT, said rimegepant succeeded in two Phase 3 trials, BHV3000-301 and BHV3000-302, enrolling 1,080 total patients. The drug, taken as a pill, bested a placebo at reducing the pain or symptoms associated with a single migraine attack. Biohaven said after a single treatment without additional rescue medications, the drug separated from placebo early and patients’ responses improved over time.
In the two studies, Biohaven enrolled patients who experience an average of 4.5 moderate to severe migraines per month. Each of those migraines last a median of 24 hours.
In study 301 19.2 percent of the 543 patients on rimegepant were pain-free 2 hours after treatment, compared to 14.2 percent of the 541 placebo patients. In study 302, 19.6 percent of the 537 patients were pain-free 2 hours, versus 12 percent of the 535 placebo patients.
Biohaven also reported 36.6 percent of those on rimegepant in study 301 and 37.6 percent of rimegepant patients in study 302 no longer had their “most bothersome symptom,” either nausea or sensitivity to light or sound, 2 hours after treatment. This compared to 27.7 percent and 25.2 percent of placebo patients in the two studies. Separation from placebo on both were the two main goals of the two trials. The company has yet to report data on a variety of secondary measures. It said there was a “numerical separation” on one of those study goals, the onset of pain relief within 30 to 45 minutes, though it didn’t specify whether those results were statistically significant. Biohaven will share additional information at medical meetings this year.
Biohaven aims to file for FDA approval of rimegepant next year, keeping pace with Allergan (NYSE: [[ticker:AGN]]), whose similar, rival drug ubrogepant has already completed one of two Phase 3 trials. But nonetheless shares fell more than 23 percent in early trading. Though its tricky to compare drugs across different clinical trials, in Allergan’s 1,327-patient study, 19.2 percent of patients on a low (50 mg) dose of ubrogepant and 21.2 percent of patients on a high (100 mg) dose were pain-free two hours after a migraine attack, compared to 11.8 percent of placebo patients. Some 38.6 percent of those on a low dose no longer had their most bothersome symptom, compared to 37.7 percent of patients on a high dose and 27.8 percent of placebo patients.
Allergan shares climbed 1.3 percent early Monday.
Migraines affect some 38 million people in the U.S. alone, according to the Migraine Research Foundation. A migraine attack can be debilitating, bringing with it sensitivity to light and sound, and visual disorientation called an aura. Though the aura typically lasts an hour, migraines can last from several hours to several days
Biohaven’s drug is a member of a new class of migraine medicines that block calcitonin gene-related peptide (CGRP), a protein thought to play a role in pain transmission. These drugs are part of two different migraine-treating races. In one race, four different injectable CGRP drugs are either in late-stage testing or undergoing an FDA review, and unlike existing migraine therapies, they are supposed to reduce the number of attacks.
In the second race, anti-CGRP pills are being developed as acute treatments for migraines, possibly providing alternatives to generic triptan pills. Triptans ease pain and are taken at the earliest signs of a migraine attack, but they only temporarily help after symptoms start and can lead to rebound headaches. Biohaven and Allergan are each developing oral CGRP blockers as alternatives, and Allergan reported results from the first of two Phase 3 trials earlier this year. (Eli Lilly’s lasmiditan, which works differently than both of these therapies, is headed for an FDA review and also in the mix.)
Both Biohaven and Allergan, incidentally, licensed their drugs from immuno-oncology rivals Bristol-Myers Squibb (NYSE: [[ticker:BMY]]) and Merck (NYSE: [[ticker:MRK]]) respectively. Biohaven grabbed rights to rimegepant and another preclinical migraine drug, BHV-3500, from Bristol-Myers in July 2016 and used the deal to help springboard to a $168 million IPO in May. Ubrogepant, meanwhile, is the result of a licensing deal between Allergan and Merck. Merck, for one, had stopped developing an older, similar drug called telcagepant in 2011 due to worrisome effects on peoples’ livers, a concern that Biohaven and Allergan have been tracking in their clinical studies.
Biohaven said today that rimegepant was no more likely than a placebo to lead to spikes in liver enzymes beyond the “upper limit of normal,” an indication of possible liver damage. In its two studies combined, 31 total patients (2.8 percent) on rimegepant had enzyme levels beyond the upper limit of normal, compared to 23 (2.1 percent) placebo patients. Nausea and urinary tract infections were the most common side effects reported.
In Allergan’s Phase 3 study, six people saw their liver enzymes spike dangerously high. Allergan at the time said there were “alternative explanations in all cases,” and that a panel of experts monitoring liver safety concluded that none “have a probable relationship to ubrogepant.”
But even if they prove safe to use over the long haul, will the various drugs succeed commercially? While encouraged about the injectable anti-CGRP medicines, for instance, migraine experts expressed concern to Xconomy last year about overestimating their potential and whether their likely high price tags might make them unaffordable. As for the new crop of anti-CGRP pills, Barclays analyst Geoff Meachem recently wrote that despite competition and “likely payer management,” there will be space for “multiple products to take share.” Meachem pegged more than $700 million in peak sales for rimegepant.
Here’s more on the questions and challenges ahead for the new group migraine drugs.
