Eli Lilly Submits NDA for Lasmiditan for Acute Treatment of Migraine

Peter Goadsby, MD, PhD, DSc, a professor of neurology at both the University of California San Francisco and King College London

Peter Goadsby, MD, PhD, DSc

Eli Lilly and Company has announced the submission of a new drug application (NDA) to the FDA for lasmiditan for the acute treatment of migraine with or without aura in adults.

The NDA is backed by data from 2 phase 3 single-attack studies (SAMURAI and SPARTAN), which evaluated the safety and efficacy of lasmiditan for the acute treatment of migraine.

“New medicines are being developed, and what we’re seeing is phase 3 studies for 2 classes: the 5-HT1F—receptor agonist and ditans—specifically lasmiditan—which turns off trigeminal pathways and doesn’t have a vessel effect; it is also clearly effective in the acute treatment of migraine,” Peter Goadsby, MBBS, told NeurologyLive when providing a historical perspective on the evolution of clinical management and new therapies.¹

In the studies, participants were randomized to a first dose of treatment (SAMURAI, 1:1:1 ratio of lasmiditan 200 mg/100 mg or placebo; SPARTAN, 1:1:1:1 ratio of lasmiditan 200 mg/100 mg/50 mg or placebo) taken within 4 hours of migraine onset, and for recurrence, participants took a randomly assigned second dose of the previously assigned intervention or placebo. The total time on study was approximately 11 weeks.

At 2 hours following the initial dose of lasmiditan, the percentage of patients with lasmiditan 200 mg (P <.001) who were migraine pain-free was significantly greater than placebo (lasmiditan 200 mg: SAMURAI 32.2%, SPARTAN 38.8%; placebo: SAMURAI 15.3%, SPARTAN 21.3%). Lasmiditan also met the key secondary endpoint, with a significantly greater percentage of patients free of their most bothersome symptom, either sensitivity to light, or sensitivity to sound or nausea, compared to placebo at 2 hours post-first dose (lasmiditan 200 mg: SAMURAI 40.7%, SPARTAN 48.7%; placebo: SAMURAI 29.5%, SPARTAN 33.5%). The results were significant across all studied doses for both endpoints.²

The most commonly reported adverse effects with lasmiditan (≥2% and greater than placebo) after the initial dose were dizziness, paresthesia, somnolence, fatigue, nausea, muscle weakness and numbness—most events were mild-to-moderate in severity. Safety outcomes were consistent across the 2 studies.

Data from these studies were presented at the American Headache Society annual meeting and the American Academy of Neurology annual meeting.

Lasmiditan, the investigational, oral, selective serotonin 5—HT_1F agonist is the first and only molecule in the ‘ditan’ class under evaluation for the acute treatment of migraine in adults. The structurally and mechanistically distinct therapy differs from other approved migraine therapies as it lacks vasoconstrictive activity. If approved, lasmiditan could represent the first significant innovation for acute treatment of migraine in more than 2 decades.

Eli Lilly also announced plans to submit a supplemental biologics license application by the end of 2018 for galcanezumab-gnlm (Emgality) for the preventative treatment of episodic cluster headaches in adults, for which the FDA granted breakthrough therapy designation.³ There are currently no approved preventative treatments for episodic cluster headache in the United States. Emgality, a calcitonin gene-related peptide antagonist, was approved in September by the FDA for the preventative treatment of migraine in adults as a once-monthly, self-administered, subcutaneous injection.⁴

REFERENCES

1. https://www.neurologylive.com/insights/chronic-migraine-current-treatment-options-and-recent-advances/historical-management-chronic-migraine

2.Wietecha L, Kuca B, Asafu-Adjei J, et al. Phase 3 Studies (SAMURAI, SPARTAN) of Lasmiditan Compared to Placebo for Acute Treatment of Migraine (S50.008). Neurology. 2018;90. http://n.neurology.org/content/90/15_Supplement/S50.008.

3.Lilly Submits New Drug Application to the FDA for Lasmiditan for Acute Treatment of Migraine, Receives Breakthrough Therapy Designation for Emgality™ (galcanezumab-gnlm) for Prevention of Episodic Cluster Headache [news release]. Indianapolis, IN: Eli Lilly and Company; Nov. 14, 2018. https://investor.lilly.com/news-releases/news-release-details/lilly-submits-new-drug-application-fda-lasmiditan-acute

4. https://www.neurologylive.com/clinical-focus/galcanezumab-fda-go-ahead-migraine-prevention