Eli Lilly Submits NDA for Lasmiditan in China for Acute Migraine Treatment

On January 29, the listing application for Eli Lilly and Company's Lasmiditan tablets was accepted by the CDE. This is an oral 5-hydroxytryptamine 1F (5-HT_1F) Agonist, used for the treatment of acute migraine with or without aura in adults.

Source: CDE Official Website

Lasmiditan was first approved for marketing by the U.S. FDA on October 11, 2019, under the trade name Reyvow. It is the first approved 5-HT1F receptor agonist. The drug targets and binds with high affinity to 5-HT1F receptors in the trigeminal pathway, penetrates the central nervous system to relieve migraine symptoms, and has no vasoconstrictive activity.

Chemical Structure of Lasmiditan

In two randomized, double-blind, placebo-controlled Phase 3 clinical trials, the SAMURAI and SPARTAN studies, which enrolled 3,177 patients with migraine, lasmiditan significantly increased the proportion of patients whose headaches completely disappeared two hours after taking the medication compared to the placebo group. It also significantly alleviated other most bothersome symptoms of migraine, namely nausea and sensitivity to sound and light. In a subgroup of patients who had an insufficient response to triptans, lasmiditan still demonstrated good efficacy. Based on this, the drug's approval for marketing became the first new mechanism small molecule pharmaceutical approved by the FDA for acute migraine treatment in twenty years.

Migraine is a very common chronic neurovascular disease. According to statistics, migraine affects nearly 14% of the global population, with about 33 million cases in the United States and approximately 13 million patients in China. Patients often experience episodes of the condition, with symptoms including headache, photophobia, phonophobia, visual disturbances, and nausea. Its economic burden ranks second among all brain-related disorders.

However, before the approval of 5-HT1F and CGRP-targeted drugs, the development of migraine medications had stalled for more than 20 years. Drugs approved before 2018 primarily targeted the 5-hydroxytryptamine system and its receptors 5-HT1D/1B, with triptans being the typical representatives and once the mainstay for treating acute migraines. Despite their significant efficacy in relieving migraines, the vasoconstrictive effects caused by the activation of the 5-HT1B receptor subtype led to a series of side effects.

In 2018, the approval of three monoclonal antibody drugs targeting the CGRP pathway brought new hope for migraine treatment. In 2019, rimegepant became the first newly approved drug based on the 5-HT1F receptor. The approval of these drugs also marks a shift in drug development strategies toward novel drug targets. CGRP receptor antagonists (gepants) and 5-HT1F receptor agonists (ditans) offer better efficacy and milder side effects compared to older drugs used for acute migraine treatment. Therefore, they are also expected to provide better outcomes for patients, alleviating the burden caused by migraines.

According to the Insight database, none of these new mechanism migraine drugs have been launched in China yet. Eli Lilly's Lasmitidan is the fastest-progressing one among them, with its first clinical trial application submitted in China in 2018, and Phase III clinical trials initiated in China in 2019. This marketing application submission means that Chinese patients are one step closer to a potentially better treatment option.

Development Status of CGRP Inhibitors in China

From Insight database (http://db.dxy.cn/v5/home/)