Rimegepant Has Small But Significant Preventive Effect On Migraines

The oral calcitonin gene-related peptide receptor (CGRP) antagonist rimegepant is effective for migraine prevention, a new phase 2/3 trial shows.

Made by Biohaven Pharmaceuticals, rimegepant is already approved for acute migraine treatment in the U.S. and several other countries.

Patients who took rimegepant every other day for 12 weeks had 0.8 fewer migraine days per month compared to those taking placebo (P=0.01), Dr. Richard B. Lipton of Albert Einstein College of Medicine in the Bronx and colleagues report in The Lancet.

"That's a significant finding because in headache medicine for decades we've drawn a bright line between acute treatments, which people take after the pain begins to relieve pain and restore function, and preventative treatments," Dr. Lipton told Reuters Health in a Zoom call.

Currently, he noted, primary acute treatments available for migraine are triptans and non-steroidal anti-inflammatory drugs (NSAIDs), and preventive medications include beta-blockers and antiepilepsy drugs.

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All were accidentally discovered to be helpful for migraine when they were used for other indications, he added, but rimegepant and five other approved medications were designed to target CGRP, a neurotransmitter implicated in migraine.

Six drugs targeting this pathway have been approved by the U.S. Food and Drug Administration (FDA) for acute migraine treatment, including four monoclonal antibodies given by injection and two oral drugs, rimegepant and ubrogepant.

In the current trial, funded by Biohaven, 747 patients at 92 U.S. sites were randomly assigned to oral rimegepant 75 mg or placebo every other day for 12 weeks, after a four-week observation phase.

By weeks 9-12, individuals on rimegepant were having 4.3 fewer migraine days each month, compared to 3.5 fewer days for the placebo group. In the rimegepant group, 49% had a reduction of at least 50% in the mean number of moderate or severe migraine days in the last month of the study, compared to 41% of the placebo group (P=0.044).

Among the 741 study participants who received either placebo or rimegepant, 36% of each group reported an adverse event. Seven patients on rimegepant and four on placebo left the study due to adverse events. There were no deaths.

"Migraine remains an underdiagnosed and undertreated disorder," Dr. Lipton said. "There really has been an explosion of new treatments over the last few years - drugs, devices, behavioral studies that are all evidence-based."

While many doctors see migraine as difficult to treat, he added, "migraine is very treatable, and the primary-care doctors I know who make an effort to diagnose and treat migraine in their patients are often regarded as heroes by their patients."

While monoclonal antibodies targeting CGRP are effective, Dr. Lipton noted, they are usually prescribed by specialists and must be injected.

The current prescription for rimegepant includes eight pills, which is not enough to use it for prevention. "The plan is to seek regulatory approval for rimegepant as a preventive medication," Dr. Lipton said. "When that regulatory approval is achieved, Biohaven, the company, hopes that people will be able to get an added amount of the drug to use it as a preventive."

In a comment accompanying the study, Dr. Lars Edvinsson of Lund University in Sweden writes: "The improvement relative to placebo associated with rimegepant on this endpoint - less than 1 monthly migraine day (MMD) - is disappointing."

The finding of a 49% responder rate with rimegepant versus 41% for placebo, he adds, "is broadly within the range of 50% responder rates for monoclonal antibodies, although caution should be taken with cross-study comparisons."

Dr. Edvinsson concluds: "There is still some way to go in understanding how the gepant class of drugs can be most effectively used."

—Anne Harding

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