BLA for Eptinezumab for Migraine Prevention Submitted to FDA

Bob Azelby, MBA, the chief executive officer of Alder

Bob Azelby, MBA

Alder Biopharmaceuticals has submitted a Biologics License Application (BLA) to the FDA for its investigational monoclonal antibody, eptinezumab, for migraine prevention.¹

The therapy targets the calcitonin gene-related peptide (CGRP), and if approved, would join 3 other medicines—erenumab (Aimovig, Amgen/Novartis), galcanezumab (Emgality, Eli Lilly), and fremanezumab (Ajovy, Teva)—in the CGRP class that have recently been granted approval. Alder stated that if the BLA is accepted, it will be on track to commercially launch eptinezumab in Q1 of 2020.

“Completing the BLA submission of eptinezumab is a significant milestone for Alder that underscores our continued mission to provide new treatment options for the millions of patients living with the debilitating effects of migraine,” said Bob Azelby, MBA, the chief executive officer of Alder. “I’m extremely grateful to all the Alder staff, physicians and other medical professionals who participated in the BLA submission process with a common goal to support patients who are looking for additional preventive treatment options.”

“If approved, eptinezumab will be the first quarterly infusion therapy for migraine prevention designed specifically for rapid, effective, and sustained suppression of migraine,” he added.

The treatment has been assessed in a number of global, randomized, double-blind, placebo-controlled clinical trials, including the PROMISE 1 and PROMISE 2 phase 3 trials.

At 1 year in PROMISE 1, epitnezumab lowered monthly migraine days by 4.3 days (baseline, 8.0) for patients treated with the 300-mg dose, following their first infusion. 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.²

Previously, the therapy reported an average reduction of ≥50% monthly migraine days from baseline in 70.7% of patients, compared to just 58.7% for patients given placebo through months 6 to 12. That was an 8.9% improvement from mean reductions reported during the first 2 quarterly doses of therapy. Another 51.5% of eptinezumab patients reached a mean monthly migraine day reduction of ≥75% from baseline, while only 38.7% of patients given placebo reported that rate—a 12.8% improvement on the reduction rate reported by patients given therapy in the first 2 quarterly doses.³

The safety profile remained consistent with previous findings, with no new safety findings observed with the third and fourth quarterly infusions. The most commonly reported adverse events (AEs), happening at a rate of ≥2.0% across all eptinezumab treatment groups, and greater than that of placebo were upper respiratory tract infection (10.5%), nasopharyngitis (6.8%), fatigue (3.2%), diarrhea (2.3%) and oropharyngeal pain (2.0%).

In total, PROMISE 1 randomized 888 qualified patients to receive either eptinezumab (300 mg, 100 mg, or 30 mg) or placebo infusion, once weekly for 12 weeks. All patients had previously experienced at ≥14 headache days per month, with ≥4 headaches meeting the International Classification of Headache Disorders 2nd Edition (ICD-II) criteria for migraine.

Meanwhile, PROMISE 2 randomized patients to either eptinezumab (300 mg or 100 mg) or placebo, administered by infusion once every 12 weeks. In total, 1072 patients received the trial drug. Those that participated in the trial had an average of 16.1 migraine days per month at baseline. Alder announced in January 2018 that the treatment had met the primary end point PROMISE 2 with very high statistical significance compared to placebo (P <.0001) for both dose levels tested, following a single quarterly infusion.⁴

Additionally, eptinezumab met all key secondary end points with statistical significance against placebo. Those end points included prevention beginning Day 1 (P <.0001) and 50% (P <.0001) and 75% (P <.0001) responder rates month 1 through month 3. As well, 15% of eptinezumab patients had no migraines for a full 3 months (P <.0001, unadjusted). Safety and tolerability were also similar to previously reported eptinezumab studies.

REFERENCES

1. Alder BioPharmaceuticals Submits Biologics License Application to the U.S. Food and Drug Administration for Eptinezumab [press release]. Bothell, WA: Alder BioPharmaceuticals; Published February 22, 2019. investor.alderbio.com/news-releases/news-release-details/alder-biopharmaceuticalsr-submits-biologics-license-application. Accessed February 21, 2019.

2. 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.

3. Saper J, Lipton R, Kudrow D, et al. Primary Results of PROMISE-1 (Prevention OfMigraine via Intravenous eptinezumab Safety and Efficacy—1) Trial: a Phase 3, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Eptinezumab for Prevention of Frequent Episodic Migraines. Neurology. 2018;90(15S):S20.001.

4. Alder Announces Eptinezumab Significantly Reduces Migraine Risk Meets Primary and All Key Secondary Endpoints in Pivotal PROMISE 2 Phase 3 Trial for Chronic Migraine Prevention [press release]. Bothell, WA: Alder BioPharmaceuticals; Published January 8, 2018. investor.alderbio.com/news-releases/news-release-details/alder-announces-eptinezumab-significantly-reduces-migraine-risk. Accessed February 21, 2019.