Alder Biopharmaceuticals’ monoclonal antibody was recently submitted in a BLA to the FDA and is on pace to hit the newly crowded preventive migraine market in early 2020.
Stephen Silberstein, MD
In February, Alder Biopharmaceuticals submitted a biologics license application (BLA) to the FDA for its flagship investigational preventive migraine treatment eptinezumab, an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody. If approved, it is expected to come to market in early 2020.1
However, the market it will be entering is becoming increasingly crowded. In 2018, 3 other CGRP-focused inhibitors—erenumab (Aimovig, Amgen/Novartis), galcanezumab (Emgality, Eli Lilly), and fremanezumab (Ajovy, Teva)—were given the FDA go-ahead, giving patients with episodic and chronic migraine several preventive options in a once bare armamentarium. What gives eptinezumab an advantage may be its dosing frequency and its time to pain-relief.
Both erenumab and galcanezumab are available in monthly doses, while fremanezumab can be administered in a monthly fashion or a triple dose administered quarterly. Eptinezumab, however, is given only in quarterly, 30-minute infusions. In a NeurologyLive® Peer Exchange panel discussion, Stephen Silberstein, MD, professor of neurology and director of the Jefferson Headache Center at Thomas Jefferson University, who is also editor in chief of NeurologyLive®, noted that physicians do not know for sure which of the dosing options is best for clinical practice, but they do offer individualization options.
“There are some patients, for example, who do not want to give themselves injections, and if you’re seeing them quarterly, that might be better,” he said. “Those are patients who don’t want to see us that often and would prefer to do it at home. We have options of drugs with different mechanisms of action, with different groups of administration and with a different frequency of administration.”
Bob Azelby, MBA, chief executive officer of Alder, has expressed the company’s confidence in the therapy’s ability to provide patients advantages over its competing products.2 Studies of the antibody have shown that its bioavailability is 100% by the end of its half-hour infusion.3 Most notably, in a number of statements, he’s touted eptinezumab’s design as focused specifically for “rapid, effective, and sustained suppression of migraine.”
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 3.4
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).
“[It has the] potential to offer both rapid and sustained suppression of migraine that is further improved for patients whose quality of life is severely impacted by this condition,” lead investigator Richard Lipton, MD, director of the Montefiore Headache Center, Albert Einstein College of Medicine, said at the time of the PROMISE 2 trial's 6-month data presentation. “My patients could potentially see great benefit from a treatment that can provide the level of efficacy seen with eptinezumab in the clinical studies.”
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.5
Previously, treatment with eptinezumab was associeated with 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 patients reached a mean monthly migraine day reduction of ≥75% from baseline, while only 38.7% of patients given placebo reported that rate, equaling a 12.8% improvement on the reduction rate reported by patients given therapy in the first 2 quarterly doses.6
With less than a year before its approval in Alder’s planned timetable, eptinezumab may also be able to compete with its price—as the market has been set for its predecessors. The list price of erenumab is $6900 per year, although, in an Institute for Clinical and Economic Review (ICER) report, an applied industry-wide average discount rate of 27% dropped its estimated annual net price to $5000.7 Likewise, both galcanezumab and fremanezumab are being sold by Eli Lilly and Teva, respectively, at list prices of $6900 per year, or $575 per month.8
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 April 17, 2019.
2. Keown A. Interview: With Less Than One Year Under His Belt, Alder CEO Eyes Becoming a Commercial Company. BioSpace website. Published April 10, 2019. biospace.com/article/with-less-than-one-year-under-his-belt-alder-ceo-eyes-becoming-a-commercial-company. Accessed April 17, 2019.
3. Baker B, Schaeffler B, Cady R, et al. Rational design of a monoclonal antibody (mAb) inhibiting calcitonin gene-related peptide, ALD403 (Eptinezumab), intended for the prevention of migraine. Poster presented at: American Academy of Neurology (AAN) 2017 Annual Meeting. April 22 to 28, 2017; Boston, MA.
4.. 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 17, 2019.
5. 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.
6. 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.
7. ICER. Calcitonin gene-related peptide (CGRP) inhibitors as preventative treatments for patients with episodic or chronic migraine: effectiveness and value: final evidence report. Published July 3, 2018. icer-review.org/material/cgrp-final-report/. Accessed January 18, 2019.
8. US FDA approves Lilly migraine drug at a price that is the same as its rivals. CNBC website. Published September 28, 2018. cnbc.com/2018/09/28/us-fda-approves-lilly-migraine-drug-at-a-price-that-is-the-same-as-its-rivals.html. Accessed April 17, 2019.