Rami Apelian and Marija Geertsen Share Insights from 9 Poster Presentations on Migraine Prevention & Treatment at AHS 2022

Shots:

Rami spoke about study design of the P-III study evaluating its lead candidate in migraine
Marija Geertsen talked about different treatment options available for migraine & neurological diseases
The interview highlights the development plans and global expansion of various therapies for brain diseases

Smriti: Explain the details (MOA, ROA, formulations, etc.) of Vyepti.

Rami Apelian: VYEPTI® (eptinezumab-jjmr) is the first and only FDA- approved intravenous (IV) infusion for the preventive treatment of migraine in adults. VYEPTI is a CGRP antagonist (anti-CGRP) that is 100% bioavailable following one 30-minute infusion every 3 months.

Smriti: Give us some insights on the study design of the P-III (PROMISE-1), (PROMISE-2) & P-IIIb (DELIVER) study evaluating Vyepti (eptinezumab).

Rami Apelian:

The efficacy and safety of VYEPTI were demonstrated in two Phase 3 clinical trials; episodic migraine in PROMISE 1 and chronic migraine in PROMISE 2. In PROMISE 1, a total of 665 patients were randomized to receive placebo (n=222), 100 mg VYEPTI (n=221), or 300 mg VYEPTI (n=222) every 3 months for 12 months. PROMISE 2 included a total of 1,072 patients who were randomized to receive placebo (n=366), 100 mg VYEPTI (n=356), or 300 mg VYEPTI (n=350) every 3 months for 6 months. The primary endpoint in each study was the change from baseline in mean monthly migraine days (MMD) over Months 1-3. In PROMISE 2, the study population included patients with a dual diagnosis of chronic migraine and medication-overuse headache, diagnosed in alignment with the ICHD-3β criteria, attributable to overuse of acute medications: triptans, ergotamine, opioids, simple analgesics or combination analgesics.
DELIVER (NCT04418765) is a Phase 3b, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of VYEPTI in patients with chronic or episodic migraine. Chronic migraine was defined as migraine occurring on ≥8 days per month and headache occurring on >14 days, and episodic migraine as migraine occurring on ≥4 days per month and headache occurring on ≤14 days. All patients had to have experienced failures of two to four prior preventive treatments. In the study, 892 patients were randomized to receive eptinezumab 100 mg or 300 mg or placebo by intravenous (IV) infusion. The primary endpoint was change from baseline in the number of monthly migraine days over weeks 1-12.

Smriti: What outcomes did the P-III (PROMISE-1), (PROMISE-2) & P-IIIb (DELIVER) study portray?

Rami Apelian: The primary endpoint was met in both studies; episodic migraine in PROMISE-1 and chronic migraine in PROMISE-2.

In PROMISE-1:

Mean migraine frequency at baseline was approximately 8.6 migraine days per month and was similar across treatment groups.
Mean change from baseline in MMD with VYEPTI compared with placebo months 1-3: -3.9 days for 100 mg (p=0.018), -4.3 days for 300 mg (p<0.001), and -3.2 days for placebo.
Percent responders with at least 50 percent reduction in MMD in months 1-3 compared with placebo: 49.8 percent for 100 mg (nominal statistical significance p=0.009), 56.3 percent for 300 mg (p<0.001), and 37.4 percent for placebo.
Percent responders with at least 75 percent reduction in MMD in months 1-3: 22.2 percent for 100 mg (p= not statistically significant), 29.7 percent for 300 mg (p<0.001), and 16.2 percent for placebo.
Greater percentage of placebo-treated patients had migraine on most days during the first 7 days of treatment compared to VYEPTI-treated patients.

In PROMISE-2:

Mean migraine frequency at baseline was approximately 16.1 migraine days per month and was similar across treatment groups.
Mean change from baseline in MMD compared with placebo months 1-3: -7.7 days for 100 mg (p<0.001), -8.2 days for 300 mg (p<0.001), and -5.6 days for placebo.
Percent responders with at least 50 percent reduction in MMD in months 1-3 compared with placebo: 57.6 percent for 100 mg (p<0.001), 61.4 percent for 300 mg (p<0.001), and 39.3 percent for placebo.
Percent responders with at least 75 percent reduction in MMD in months 1-3: 26.7 percent for 100 mg (p<0.001), 33.1 percent for 300 mg (p<0.001), and 15.0 percent for placebo.
Greater percentage of placebo-treated patients had migraine on each individual day during the first 7 days of treatment compared to VYEPTI-treated patients.

The safety of VYEPTI was evaluated in 2,076 patients with migraine who received at least one dose of VYEPTI. The most common adverse reactions (≥2 percent and at least 2 percent or greater than placebo) in the clinical trials for the preventive treatment of migraine were nasopharyngitis and hypersensitivity.

At the 64^th Annual Scientific Meeting of the American Headache Society, two separate post-hoc analyses from the pivotal PROMISE-1 and PROMISE-2 studies showed eptinezumab was associated with a sustained downward shift in diagnostic frequency of episodic and chronic migraine (measured by monthly headache days) vs. placebo across 6 months of treatment, and subsequent dosing of eptinezumab may provide benefits for patients who initially have suboptimal response.

Further, an exploratory subpopulation analysis of the Phase 3b DELIVER study evaluated the efficacy and safety of eptinezumab for the prevention of migraine in patients with 2-4 previous preventive treatment failures. Prespecified patient subgroups included medication-overuse headache (MOH) diagnosis, disease classification, number of previous treatment failures, and sex. Patients treated with eptinezumab demonstrated larger reductions in monthly migraine days (MMDs) from baseline through week 12 than patients receiving placebo across all subgroups. Mean MMDs for patients with episodic migraine decreased by 3.1 days (100mg; n=162) and 4.0 days (300mg; n=158) versus 1.0 day for placebo (n=164). For patients with chronic migraine, mean MMDs decreased by 6.5 days (100mg; n=137) and 6.6 days (400mg; n=134) versus 3.3 days for placebo (n=134). And, for patients with medication overuse headache, mean MMDs decreased by 5.6 days (100mg; n=38) and 7.3 days (300mg; n=35) versus 2.3 days (placebo; n=37). The safety profile of eptinezumab was consistent with the safety profile observed in the pivotal Phase 3 PROMISE-1 and PROMISE-2 studies of eptinezumab for the preventive treatment of migraine in adults.

Smriti: How has the presentation at the AHS contributed towards bringing Vyepti to the attention of migraine sufferers?

Marija Geertsen: Lundbeck had nine poster presentations at this year’s American Headache Society Annual Meeting reinforcing the scientific evidence for VYEPTI® (eptinezumab-jjmr) as a preventive migraine treatment in adults. These data continue to show and support the clinical benefit of VYEPTI as a preventive treatment option for adults with migraine, both from clinical research and real-world evidence perspective. For those who are highly impacted by migraine and seeking different treatment options, VYEPTI may offer an option to help break the vicious cycle of more frequent migraine days with continued increasing need for acute medications over time.

Smriti: As Lundbeck is focused on providing treatment options for various neurological diseases, would you please give our readers a highlight of your pipeline for such therapies?

Marija Geertsen: Lundbeck has significant R&D efforts focused on advancing the scientific body of evidence for VYEPTI. We have additional trials for chronic migraine and medication overuse headache (MOH), as well as our in-progress investigational Phase 3 trial to evaluate the safety and efficacy of eptinezumab in episodic cluster headache in the ALLEVIATE study.

From our Phase 2 pipeline, Lu AG09222 is an investigational monoclonal antibody designed to bind and inhibit signaling mediated by pituitary adenylate cyclase-activating polypeptide (PACAP); a neuropeptide that is implicated in migraine pathophysiology.

Further, we are progressing with Lu AG22515, a CD40L inhibitor which interferes with the activation of the adaptive immune response by blocking the CD40L/CD40 co-stimulatory interaction on immune cells. We have started clinical studies for this program, which accelerates our R&D strategy within neuroimmunology.

Smriti: Today migraine is a common disease among individuals with many treatment options available, how will Lundbeck’s Vyepti & other therapies stand out from the competition?

Marija Geertsen: VYEPTI is the only FDA-approved IV infusion for the preventive treatment of migraine in adults. VYEPTI provides fast and powerful migraine prevention that’s proven to reduce monthly migraine days from the very first treatment, with sustained effect over 24 weeks, as demonstrated in two Phase 3 clinical trials. There are many treatment options, but migraine disease is different for everyone and can be unrelentless. VYEPTI has a well understood efficacy and safety profile with consistent data supporting its preventive use among adult migraine patients

Smriti: Tell us more about Lundbeck’s development plans for Vyepti.

Marija Geertsen: As of the first quarter in 2022, VYEPTI has been authorized in 41 markets around the world, and review is ongoing with several regulatory agencies. In our global expansion for VYEPTI, we are conducting a clinical trial program to support filings in China and Japan with the SUNLIGHT, SUNRISE and SUNSET studies.

Source: Canva

About the Authors:

Rami Apelian

Rami Apelian, MD, MPH, FAES is Medical Director at Huntington Headache and Neurology based in Arcadia, California. Throughout his nine years in private practice, Dr. Apelian has specialized in diagnosing and treating a number of neurological disorders with particular interests in epilepsy and headache disorders. He provides effective treatment by utilizing a cutting-edge approach for patients suffering from a wide array of neurological disorders.

Marija Simin Geertsen

Marija Simin Geertsen is the Vice President, Medical Affairs at Lundbeck US. She has 15+ years of industry experience in medical leadership roles. Marija translates environmental insights into medical strategies for meaningful drug development and impactful evidence communication. She earned MD from University of Medicine, Rijeka, Croatia and MBA from AVT Business School.