PHILADELPHIA – The oral, small molecule, calcitonin gene-related peptide receptor antagonist ubrogepant, currently under regulatory review for approval as a treatment for acute migraine headache, was as effective for migraine relief in patients with a history of triptan ineffectiveness as it was in patients for whom triptans had been effective, based on a post hoc analysis of data collected from 1,798 patients enrolled in two phase 3 trials.
Mitchel L. Zoler/MDedge News
Dr. Susan Hutchinson
In the roughly one-quarter of all patients who had a clinical history consistent with triptan ineffectiveness, one 50-mg dose of ubrogepant led to pain freedom 2 hours after treatment in 16% of patients, compared with a response rate of 8% in placebo-treated patients. Ubrogepant’s effectiveness rate that was about the same as seen in patients with a history of triptan effectiveness, who were about 37% of the study population, Susan Hutchinson, MD, said at the annual meeting of the American Headache Society.
Among those with a history of triptan effectiveness, 20% were pain free after 2 hours, compared with 11% of placebo-treated controls, said Dr. Hutchinson, a family physician and headache specialist who practices in Irvine, Calif. Both of these between-group differences were statistically significant. The remaining patients included in the analysis had no triptan history, and among these patients a single, 50-mg dose of ubrogepant produced pain freedom at 2 hours in 24% of patients, versus an 18% response in placebo-treated controls, a difference that fell short of statistical significance.
The analysis Dr. Hutchinson reported came from data collected in two pivotal trials of ubrogepant for treatment of an acute migraine headache, the ACHIEVE I and ACHIEVE II trials, which together randomized more than 2,600 migraine patients eligible for the study’s modified intention-to-treat analysis, and 1,798 patients from that analysis who received a 50-mg dose of ubrogepant or placebo. In March 2019, the company developing ubrogepant, Allergan, announced that the Food and Drug Administration had accepted the company’s application for marketing approval of ubrogepant as a treatment for acute migraine largely based on data from ACHIEVE I and ACHIEVE II.
The researchers defined a history of triptan ineffectiveness as a patient who never used a triptan because of a warning, precaution, or contraindication, a patient who recently used triptans but did not achieve pain freedom within 2 hours more than half the time taking the drugs, or a patient who no longer used triptans because of adverse effects or lack of efficacy. Patients who had used triptans in the past and had complete pain relief within 2 hours more than half the time were deemed triptan-effective patients.
The analysis also looked at two other endpoints in addition to complete pain freedom: complete relief of the most-bothersome symptom of the migraine headache (photophobia for most patients), which resolved in 39% and 36% of the triptan-effective and triptan-ineffective patients, respectively, compared with placebo response rates of 27% and 23%; both between-group differences were statistically significant. A third measure of efficacy was some degree of pain relief after 2 hours, which occurred in 62% of patients in whom triptans were effective and 55% in those in whom triptans were ineffective, which were again statistically significant higher rates than among patients who received placebo.
Safety findings from the two ubrogepant pivotal trials showed good drug tolerability, with no treatment-related serious adverse events, and a profile of modest numbers of treatment-related and total adverse events similar to what occurred among patients who received placebo.
ACHIEVE I and II were funded by Allergan, the company developing ubrogepant. Dr. Hutchinson has been an adviser to and a speaker on behalf of Allergan and several other companies.
SOURCE: Blumenfeld AM. Headache. 2019 June;59[S1]:1-208, Abstract IOR02.