Ubrogepant cuts headache pain, symptoms in acute migraine
The oral CGRP* receptor antagonist ubrogepant significantly reduced headache pain and bothersome migraine-associated symptom of a single-attack, acute migraine, according to the ACHIEVE** I study presented at AAN 2018.
As the number of options available for treating migraine is limited, a fast-acting therapy that is well tolerated with migraine-specific mechanism of action will bring more treatment options for the condition, said Dr Joel Trugman, a neurologist at the University of Virginia Medical Center, Charlottesville, Virginia, US.
In the multicentre, double-blind, parallel-group, phase III study, 1,672 patients (mean age 40.7 years, 87.5 percent female, 82.4 percent Caucasian) with a history of migraine (with or without aura) were randomized in a 1:1:1 ratio to receive placebo or ubrogepant 50 mg or 100 mg to treat a single migraine attack of moderate or severe intensity within 60 days. [AAN 2018, abstract 008]
Among the 1,327 patients in the intention-to-treat population, significantly more patients in the ubrogepant arm were free from headache pain 2 hours after the initial dose compared with the placebo arm (19.2 and 21.2 percent vs 11.8 percent for ubrogepant 50 mg and 100 mg vs placebo, respectively; p=0.0023 and p=0.0003 for each comparison).
Also, the coprimary endpoint of the most bothersome migraine-associated symptom (MBS) was absent in more patients receiving ubrogepant than placebo (38.6 percent and 37.7 percent vs 27.8 percent; p=0.0023 for both comparisons). The most common MBS reported during treatment was photophobia (56.4 percent), followed by phonophobia (22.3 percent), and nausea (20.9 percent).
In terms of safety (population, n=1,436), comparable adverse event profile was observed between the ubrogepant and placebo arms. Nausea, somnolence, and dry mouth were the most common adverse events reported within 48 hours of dosing, but the incidence rates were low at <5 percent for all.
According to the researchers, there did not appear to be hepatoxicity signal with ubrogepant in the study, although they noted six cases of ≥3 time the upper limit of normal ALT and AST*** elevation, of which two were considered “possibly related” and the rest “unlikely” to be related to study drug.
“Both [the] coprimary efficacy endpoints were met with clinically meaningful effects on migraine headache pain and MBS. Ubrogepant was well-tolerated with no identified safety concerns,” concluded Trugman and co-authors.
Ubrogepant blocks the receptors for CGRP, a neurotransmitter released excessively in response to inflammation during a migraine attack, which can increase sensitivity to pain.
Being a small-molecule, orally available drug, ubrogepant is different from the monoclonal antibodies currently under development for migraine prevention, according to Trugman. As small-molecule drugs are rapidly absorbed and cleared from the system within 24 hours, they can be safer than having monoclonal antibody therapy in the long term, he added.
Nonetheless, session chair Dr Natalia Rost of Harvard Medical School, Boston, Massachusetts, US, suggested that a head-to-head clinical trial be done to compare ubrogepant and a comparator drug such as triptan that is already on the market.