Two Phase III studies for ubrogepant for the acute treatment of migraine are completed. Allergan plc

Allergan plc has announced the completion of two positive safety and tolerability studies of ubrogepant for the acute treatment of migraine. The first study (UBR-MD-04) evaluated the long-term safety and tolerability of ubrogepant (50 mg and 100 mg) compared to usual care for the acute treatment of migraine in adults for one year.The second study (3110-105-002) evaluated the hepatic safety and tolerability of ubrogepant 100 mg compared to placebo in healthy study participants over eight weeks.

Study UBR-MD-04 : UBR-MD-04, a multicenter, randomized, open-label extension study, included 1,254 U.S. adult patients (ITT population) with migraine who had been enrolled in and completed one of the previous pivotal studies for ubrogepant: ACHIEVE I or ACHIEVE II. Both 50 mg and 100 mg doses were administered orally to treat up to 8 migraine attacks every 4 weeks for one year. Patients had the option to take a second dose of ubrogepant or rescue medication if the patient had either a nonresponding migraine or a migraine recurrence. This open-label study had a usual care control arm in which patients were instructed to treat their migraine with medication(s) that they routinely used to relieve a migraine attack. Of the 1,230 patients in the safety population, approximately 76% of patients completed the 52-week treatment period with similar rates of completion across all the groups. Over the course of the study, 21,454 migraine attacks were treated with 31,968 doses of ubrogepant. The mean number of migraine attacks treated over the 52-week period was 25.5 (50 mg) and 27.2 (100 mg). In this study, ubrogepant was well tolerated with an adverse event profile similar to usual care arm. The most common adverse events ( greater than 5%) were nasopharyngitis, upper respiratory tract infection, sinusitis, urinary tract infection, and influenza. In terms of hepatic safety, no signal of drug-induced liver injury or a hepatic safety concern was observed.

Study 3110-105-002 : Study 3110-105-002, a multi-center, randomized, double-blind, placebo-controlled trial, included 516 healthy participants (adults ages 18 to 50) for a duration of 8 weeks. Study 3110-105-002 was conducted based on FDA recommendations to complete a hepatic safety study. Ubrogepant was administered intermittently (2 days of consecutive treatment with ubrogepant 100 mg, alternating with 2 days of placebo) to reflect the episodic nature of migraine and mimic the way in which patients often experience and treat migraine attacks. Of the 516 participants in the safety population, approximately 98% completed the 8-week treatment period with nearly identical rates of completion across all groups. In this study, ubrogepant was well tolerated with an adverse event profile similar to placebo. The most common adverse events ( greater than 5%) were headache, oropharyngeal pain, and nasopharyngitis. In terms of hepatic safety, no signal of drug-induced liver injury or a hepatic safety concern was observed.

Comment: Based on the completion of these safety studies for ubrogepant and previously reported efficacy and safety results from the ubrogepant ACHIEVE I (UBR-MD-01) and ACHIEVE II (UBR-MD-02). studies, Allergan will submit a New Drug Application (NDA) to the FDA) by the first quarter of 2019. Allergan anticipates that the ubrogepant NDA will be the first oral CGRP receptor antagonist submitted in the U.S. for the acute treatment of migraine with or without aura.