Monday, July 2, 2018

New medications for migraine therapy

Researchers reported that a developmental drug relieved migraine pain within two hours for more than one in five patients at the 60th Annual Scientific Meeting of The American Headache Society in San Francisco last weekend.

Rimegepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist. A neuropeptide, CGRP has been implicated in the pathogenesis of migraines, and much of the research presented at the AHS meeting this year focused on new agents that selectively affect CGRP to prevent or treat migraines.

The double-blind, placebo-controlled, multicenter study enrolled 1162 patients with a history of migraines. Researchers randomized participants to receive 75 mg of rimegepant (582) or placebo (580), and to take one dose to treat a single migraine attack that had reached moderate to severe intensity.

Two hours after taking the dose, 19.2% of patients in the rimegepant arm reported freedom from pain, compared to 14.2% of those in the placebo arm, according to the study. Participants who took rimegepant also reported higher rates of freedom from the most bothersome symptoms than those who took placebo, 36.6% vs 27.7%. More than half of those who took the study drug experienced pain relief (56%) compared to 45.7% of those who took placebo. Rimegepant also provided more sustained pain relief, up to 48 hours, than placebo, and a significantly larger proportion of patients who took rimegepant achieved normal function within two hours.

Rimegepant and placebo had similar safety and tolerability profiles, with no adverse events impacting more than 1% of patients in the rimegepant group, and no serious adverse events seen in patients who had received rimegepant.

Two phase 3 trials show that lasmiditan, a novel serotonin agonist, relieves migraine headache pain and other symptoms within two hours for many patients. The results were presented this weekend at the 60th Annual Scientific Meeting of The American Headache Society in San Francisco.

Because lasmiditan, a 5-HT1F agonist, does not constrict blood vessels, it could be used to treat migraines in patients who have cardiovascular disease or risk factors. 

The randomized, double-blind, placebo-controlled SPARTAN and SAMURAI studies enrolled patients who had between three and eight migraines each month, and moderate disability as measured by a Migraine Disability Assessment Score of 11 or more. In the SAMURAI study, researchers randomized patients to either 200 mg or 100 mg of lasmiditan or placebo. The SPARTAN study randomized participants to 200 mg, 100 mg or 50 mg of lasmiditan or placebo. Patients could take a randomly assigned second dose of either lasmiditan or placebo for rescue or recurrence.

In both studies, a much higher percentage of patients who received 200 mg of lasmiditan (32.2%-38.8%) experienced total relief from headache pain than those who received placebo (15.3%-21.3%). More patients in the 200 mg lasmiditan arms (40.7%-48.7%) also had rapid resolution of other bothersome symptoms of migraine compared to patients in the control arms (29.5%-33.5%). More patients in the 100 mg and 50 mg of lasmiditan arms also had prompt relief from headache and other symptoms compared to those in the placebo arms.

The most common adverse effects experienced by patients receiving lasmiditan included dizziness, paresthesia, somnolence, fatigue, nausea and lethargy.

Several antibodies that target the calcitonin gene-related peptide (CGRP) pathway have received U.S. Food and Drug Administration approval for use in migraine based on short-term studies. Now, research shows that patients can safely use at least one of them on a long-term basis.

Patients experienced no unexpected adverse effects during an ongoing five-year open label extension study of erenumab, according to a presentation at the 60th Annual Scientific Meeting of The American Headache Society this weekend in San Francisco. 

After participation in a 12-week double-blind, placebo-controlled study of the CGRP-pathway antibody, 383 patients enrolled in the open-label extension. Researchers conducted the interim analysis after all participants had three years of exposure or had discontinued the study. At data cutoff, 235 (61.3%) remained enrolled. All participants received erenumab for more than one year, and the median exposure was 3.2 years. Participants that continuined in the study had 3.2 years to 3.9 years of exposure.

The most common adverse effects included upper respiratory tract infections, sinusitis, influenza and back pain. Serious adverse effects occurred at a rate of 4.2 per 100 patient years. One patient died during the first year of the study extension, before an amendment to the study protocol, and that death was confounded by comorbidities. Researchers found no increase in cardiovascular events, significant change in blood pressure or heart rate.

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