Alder stated that it expected to receive a PDUFA action date within 74 days of the submission for eptinezumab and is planning a commercial launch of the anti-CGRP agent by early 2020.
Bob Azelby, MBA
The FDA has accepted a biologics license application for eptinezumab, an anti-calcitonin gene-related peptide (CGRP) preventive migraine treatment, according to its manufacturer, Alder Biopharmaceuticals.1
Alder stated that it expected to receive a Prescription Drug User Fee Act (PDUFA) action date within 74 days of the submission and is planning a commercial launch of the agent by early 2020. The BLA is supported by data from the PROMISE 1 and PROMISE 2 phase 3 clinical trials, as well as an open-label safety study and a pharmacokinetic study, among other data sets.
“Migraine is far more than a headache, it’s a serious neurological disease with a debilitating impact to patients that can lead to other issues including depression, anxiety, and sleep disturbances,” said Bob Azelby, MBA, Alder’s president and chief executive officer. “The FDA’s acceptance of our BLA is an important milestone, and the company remains focused on supporting the application review for the first quarterly infusion therapy for patients suffering from episodic and chronic migraine. In the meantime, we continue to make substantial progress scaling our medical, manufacturing and commercial infrastructure to enable a successful launch of eptinezumab for migraine patients, if approved.“
Azelby told NeurologyLive®
that the PROMISE 2 data—which showed that 60% and 33% of patients who averaged 16 migraines per month at baseline dropped to ≤8 migraines or ≤4 migraines per month after treatment, respectively—is the key to displaying the efficacy of eptinezumab. The therapy is an intravenous (IV) quarterly infusion, with 100% bioavailability after the 30-minute infusion.
“The ability to start preventing migraines within 24 hours—that, to us, is a really critical component and differentiation. Additionally, the fact that it’s done on a quarterly basis allows it to match up to when patients actually go to see their clinician,” Azelby explained. Stephen Silberstein, MD, director, Jefferson Headache Center at Jefferson University Hospital, and a primary investigator of eptinezumab, added that the IV formulation provides rapid, long-lasting relief for patients with migraine, and "there may be some economic benefits of the drug based on the formulation," he told NeurologyLive
In the PROMISE 2 trial, part of eptinezumab’s phase 3 development, the monoclonal antibody met all primary and key secondary end points with statistical significance against placebo, including prevention beginning Day 1 (P
<.0001) and 50% (P
<.0001) and 75% (P
<.0001) responder rates from month 1 through month 3.2
Altogether, 15% of patients who received eptinezumab had no migraines for 3 months (P
<.0001, unadjusted). The data also showed a reduced number of average migraines per month in patients with both episodic migraine (≤14 migraines) and chronic migraine (≥15 migraines).
In PROMISE 1, treatment with eptinezumab lowered monthly migraine days by 4.3 days (baseline, 8.0) for patients treated with the 300-mg dose, following their first infusion, at 1 year. Comparatively, those treated with placebo experienced reductions of 3.2 days (P
= .0001). Additionally, about 31% of patients treated with the CGRP inhibitor achieved a 100% reduction of migraine days from baseline on average per month, compared to about 21% of patients administered placebo.3
“What’s really important is that we have to do a better job of making sure we educate society that this is not just this devastating pain,” Azelby said. “It’s impacting their light sensitivity, their sound sensitivity, these people are nauseous, and they’re vomiting. In fact, when you get into the chronic migraine setting with multiple migraines a week, it starts to impact your sleep, anxiety, depression—you’re living with migraine every day, it’s not just the day of the attacks.”
The Alder CEO told NeurologyLive®
what was surprising in the subanalysis of eptinezumab was its efficacy across the whole spectrum of patients. “The interesting thing was we didn’t find anything. The fact that it was consistent across all patients, whether it be age, weight, works in [medication overuse patients]—we’re really pleased in the consistency of the data, not only in terms of the efficacy in general but in the subpopulations,” he explained.
"I'm very excited about a new formulation for delivering adequate treatment to people with migraine," Silberstein added.
1. U.S. Food and Drug Administration Accepts Biologics License Application for Eptinezumab [press release]. Bothell, WA: Alder Biopharmaceuticals; Published April 22, 2019. apnews.com/Globe%20Newswire/aec7efbe2d63f19fec40791661eb4c6b. Accessed April 23, 2019.
2. Alder BioPharmaceuticals® Presents New Six-Month Data for Eptinezumab Demonstrating Improvement in Efficacy in PROMISE 2 Phase 3 Trial for Chronic Migraine [press release]. Bothell, WA: Alder Biopharmaceuticals; Published June 29, 2018. investor.alderbio.com/news-releases/news-release-details/alder-biopharmaceuticalsr-presents-new-six-month-data. Accessed April 23, 2019.
3. Alder Biopharmaceuticals Presents New One-Year Data for Eptinezumab from PROMISE 1 Phase 3 Trial Demonstrating Long-Term Efficacy in Episodic Migraine [press release]. Bothell, WA: Alder BioPharmaceuticals; Published June 29, 2018. globenewswire.com/news-release/2018/06/29/1531751/0/en/Alder-BioPharmaceuticals-Presents-New-One-Year-Data-for-Eptinezumab-from-PROMISE-1-Phase-3-Trial-Demonstrating-Long-Term-Efficacy-in-Episodic-Migraine.html. Accessed February 21, 2019.