PHILADELPHIA – An intravenous formulation of a calcitonin gene–related peptide inhibitor monoclonal antibody showed efficacy for preventing chronic migraine headaches for 3 months in a dose-ranging, phase 3 trial with 1,072 patients.
In a separate study with 669 patients, a single IV dose of the antibody, eptinezumab, also significantly reduced the incidence of episodic migraine headaches during 3 months of follow-up, compared with placebo. And in both the chronic and episodic migraine studies a similar 3-month effect resulted from a second IV dose of the humanized antibody that binds the calcitonin gene–related peptide (CGRP) ligand, thereby blocking the pathway, Laszlo L. Mechtler, MD, and his associates reported in a poster at the annual meeting of the American Headache Society.
Eptinezumab follows the therapeutic approach already used by three Food and Drug Administration–approved monoclonal antibody drugs that cut migraine headache recurrences by blocking the CGRP pathway by binding either the peptide ligand or its receptor: erenumab-aooe (Aimovig), fremanezumab-vfrm (Ajovy), and galcanezumab-gnlm (Emgality). Eptinezumab differs from the three approved CGRP antibodies by using an IV route of administration – the other three are delivered by subcutaneous injection – and by a 3-month dosing interval. Both erenumab-aooe and galcanezumab-gnlm are labeled for monthly administration only, while fremanezumab-vfrm is labeled for both monthly and once every 3 months dosing schedules.
The PROMISE-1 (A Multicenter Assessment of ALD403 in Frequent Episodic Migraine) trial randomized 669 patients with episodic migraine (defined as 4-14 headache days/month with at least 4 classifiable as migraine headache days) at 87 centers mostly in the United States and with some in Georgia. The PROMISE-2 (Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine) trial randomized 1,072 patients with chronic migraine (defined as a history of 15-26 headache days/month and with at least 8 of the days involving a migraine headache) at any of 145 study sites, many in the United States, in several countries.
In PROMISE-1, patients could receive as many as four serial infusions every 3 months, and up to two serial infusions in PROMISE-2, but the primary endpoint in both studies was the change in monthly migraine count from baseline during the 3 months following the first dosage.
Among patients with chronic migraine in PROMISE-2, the average monthly migraine number fell by 8.2 migraine days/month, compared with an average 5.6 monthly migraine days drop from baseline among placebo patients, which was a statistically significant difference for the higher dosage of eptinezumab tested, 300 mg. A 100-mg dose linked with an average 7.7 migraine days/month reduction, also a statistically significant difference from the placebo patients, reported Dr. Mechtler, professor of neurology at the State University of New York at Buffalo and medical director of the Dent Neurologic Institute in Buffalo, and his associates.
Among patients with episodic migraine in PROMISE-1, the 300-mg dosage cut monthly migraines by an average 4.3 migraine headache days/month, compared with 3.2 in the placebo group, a statistically significant difference. Among patients who received the 100-mg dosage, the average cut was 3.9 migraine headache days/month, also a statistically significant difference from the placebo controls.
The researchers included no safety findings in their report, but in an interview Dr. Mechtler said that eptinezumab showed an excellent safety profile that was consistent with what’s been previously reported for the approved agents from this class. He cited the safety of the drugs in the class as a major feature of their clinical utility.
PROMISE-1 and PROMISE-2 were sponsored by Alder BioPharmaceuticals, the company developing eptinezumab. Dr. Mechtler has been a speaker on behalf of Allergan, Amgen/Novartis, Boston Biomedical, Promius, Avanir, and Teva, and he has received research funding from Allergan, Autonomic Technologies, Boston Biomedical, and Teva.
SOURCE: Mechtler LL et al. Headache. 2019 June;59[S1]:34, Abstract P12