Results of the phase 3 ACHIEVE I trial showed a high percentage of patients were free from their most bothersome symptoms 2 hours post dose.
Richard B. Lipton, MD
Results from the phase 3 ACHIEVE I study of ubrogepant, an oral, calcitonin gene-related peptide receptor antagonist developed by Allergan, demonstrate that the drug provides significant relief from pain and most bothersome symptom 2 hours post dose in patients with acute migraine.1
Ubrogepant’s new drug application was accepted by the FDA in March based on supporting data from the ACHIEVE I and II trials. In November, results of ACHIEVE II, which examined smaller doses of ubrogepant 25 mg and 50 mg compared with placebo, were published in the Journal of the American Medical Association. The study results showed that both doses were effective, with patients reporting significant rates of pain freedom and freedom from most bothersome symptom at 2 hours postdose.
ACHIEVE I was a multicenter, double-blind, placebo-controlled study (NCT02828020) that included 1672 patients with migraine (mean age 40.5 years, 88.2% women) who were randomly assigned 1:1:1 to either a 50 mg ubrogepant (n=556), 100 mg ubrogepant (n=557), or placebo (n=559). Patients received an initial dose, with an option to receive a second if they continued to experience migraine symptoms. Among the group of patients randomized, 345 (20.6%) were excluded from the efficacy analyses due to not partaking in trial treatment, not recording a baseline, or not recording postdose migraine severity or symptoms. Ultimately, the modified intention-to-treat population included 1436 participants.
At 2 hours postdose, patients were assessed on freedom from pain and absence of the most bothersome migraine-associated symptom. Secondary endpoints included sustained pain relief (from 2 to 24 hours), sustained freedom from pain (from 2 to 24 hours), pain relief at exactly 2 hours, and whether patients experienced migraine-associated symptoms such as photophobia, phonophobia, and nausea at 2 hours.
Among the 3 dose groups, 19.2% of patients in the 50 mg ubrogepant group (P = .002, adjusted for multiplicity, for comparison with placebo), 21.2% of patients in the 100 mg ubrogepant group (P <.0001) and 11.8% of patients in the placebo group experienced freedom from pain at 2 hours after the initial dose. At 2 hours, 38.6%, 37.7% and 27.8% of patients in the 50 mg, 100 mg, and placebo groups had freedom from the most bothersome symptom respectively.
"Based on the recently published ACHIEVE I and ACHIEVE II data, I am confident that ubrogepant, with its novel mechanism of action as a gepant, will make a difference for people with migraine and unmet needs for acute treatment," Richard B. Lipton, MD, who co-authored the trials, said in a statement.2 "The favorable safety and tolerability profile, as well as the efficacy data for ubrogepant are particularly important as we consider new treatment options for people living with migraine,” added Lipton, who is professor and vice chair of neurology at the Albert Einstein College of Medicine and Montefiore Health System, and director of the Montefiore Headache Center.
At 48 hours post initial dose, 12.9% of participants (185 of 1436 participants) reported an adverse event. Within 30 days of any dose, the number of patients who reported an adverse event rose to 26.3% (378 of 1436 participants). Among patients treated with 100 mg of ubrogepant, 28.7% reported an adverse event, the most of the 3 groups. The most common adverse events during the trial were nausea (occurred in 44 of 1436 participants), somnolence (20 of 1436 participants), and dry mouth (16 of 1436 participants). A total of 5 patients across the 3 groups experienced a serious adverse event, though none were recorded within 48 hours after the first dose.
“We are proud of the research and science that have brought us to this point and look forward to continuing innovation in the pursuit of migraine freedom," Mitchell Mathis, MD, chief medical officer, central nervous system at Allergan, said in a statement.2
1. Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the treatment of migraine. N Engl J Med. 2019;381:2230-224 doi:10.1056/NEJMoa1813049.
2. Allergan announces positive phase 3 ACHIEVE I trial results for ubrogepant published in the New England Journal of Medicine [news release]. Dublin, Ireland: Allergan. December 4, 2019. Accessed December 5, 2019.