Literature Review

More phase 3 ubrogepant data published as FDA decision nears


 

FROM THE NEW ENGLAND JOURNAL OF MEDICINE

About 20% of patients who receive tablets containing 50 mg or 100 mg of ubrogepant for the acute treatment of migraine are pain free 2 hours later, compared with 12% of patients who receive placebo, according to phase 3 trial results published Dec. 4 in the New England Journal of Medicine. In addition, about 38% of patients who receive ubrogepant no longer have their most bothersome migraine-associated symptom, such as photophobia, phonophobia, or nausea, at 2 hours, compared with 28% of patients who receive placebo, said David W. Dodick, MD, and colleagues.

Dr. David W. Dodick, director of the headache, sports neurology, and concussion programs, Mayo Clinic, Phoenix.

Dr. David W. Dodick

Dr. Dodick, professor of neurology at the Mayo Clinic in Phoenix, and his coauthors described efficacy and safety results from the ACHIEVE I trial. Another phase 3 study of ubrogepant, ACHIEVE II, was published in JAMA in November. That trial evaluated 25- and 50-mg doses of ubrogepant versus placebo and found rates of pain freedom and absence of the most bothersome symptom in the placebo and active treatment arms that were similar to those in ACHIEVE I.

Assessing a gepant for acute migraine treatment

Ubrogepant is an oral calcitonin gene–related peptide (CGRP) receptor antagonist. Allergan, the company developing the drug, has said it expects the Food and Drug Administration to decide in December whether to approve the drug.

To compare ubrogepant 50 mg, ubrogepant 100 mg, and placebo for the acute treatment of migraine, investigators conducted the randomized ACHIEVE I trial. Researchers enrolled 1,672 adults with migraine with or without aura. They excluded patients with clinically significant cardiovascular or cerebrovascular disease. During the trial, patients treated a single migraine attack, and they had the option to take a second dose. In all, 1,436 participants took an initial dose. Patients had an average age of 40.5 years, about 88% were women, and 82% were white.

In ACHIEVE I, the most common adverse events within 48 hours of treatment were nausea, somnolence, and dry mouth, and these events occurred more frequently in the 100-mg–dose group, Dr. Dodick and colleagues reported. Among patients who received ubrogepant, serious adverse events more than 48 hours after treatment but within 30 days of treatment included appendicitis, spontaneous abortion, pericardial effusion, and seizure. No serious adverse events occurred in the placebo group.

The authors noted that, “there was no active comparator and no evaluation of consistency of effect across multiple migraine attacks; therefore it is not possible to determine whether the drug is more or less effective than standard therapies or consistently effective with repeated use.” In addition, “safety and side-effect data from this trial were based on evaluation of a single attack, and therefore safety after repeated use cannot be inferred; an extension trial has assessed the long-term safety of ubrogepant,” they said.

The present trial was performed well, commented Alan M. Rapoport, MD. “The coprimary endpoints of pain freedom and most bothersome symptom freedom, both at 2 hours after dosing, were statistically superior for both doses of ubrogepant versus placebo,” he said. “Some of the secondary endpoints, such as pain relief at 2 hours post dose and sustained pain relief from 2 to 24 hours, were statistically better than placebo.”

Dr. Alan M. Rapoport, clinical professor of neurology at the David Geffen School of Medicine at UCLA in Los Angeles and editor-in-chief of Neurology Reviews

Dr. Alan M. Rapoport

“Based on this data, I suspect that the FDA would approve this gepant after appropriate safety data,” said Dr. Rapoport, clinical professor of neurology at the University of California, Los Angeles and editor-in-chief of Neurology Reviews. “Many more patients need to take this drug before we can be sure it is safe and effective.”

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