番茄社区

SAN FRANCISCO -- Lasmiditan, a new type of drug for acute treatment of migraine, provided prompt relief of pain and other bothersome symptoms as soon as an hour after administration, researchers reported here.

About 20% of patients treated with the highest dose of lasmiditan in one of two phase III trials reported being free of headache pain at 1 hour post-treatment, rising to nearly 40% at 2 hours.

The results were presented at the American Headache Society annual meeting.

Lasmiditan could potentially represent the first major innovation for the treatment of acute migraine in two decades. The drug is a serotonin agonist selective for the 5-HT_1F receptor. Triptans activate that receptor, but they are also active at other 5-HT receptor subtypes that are believed to be responsible for these agents' unwanted cardiovascular effects.

In the current study with lasmiditan, cardiovascular effects were nearly absent.

These phase III results follow the recent approval of the first of another new class of migraine drugs, the calcitonin gene-related peptide (CGRP) inhibitors. Other research presented at the meeting showed that lasmiditan inhibits the release of CGRP from central and peripheral trigeminal nerve terminals in the mouse brain to the same degree as sumatriptan.

"This is an incredibly exciting time to be in the headache field. So much is happening. This is a golden age for people with migraines," AHS scientific program committee chair Peter Goadsby, MD, PhD, told reporters during an advance media briefing ahead of the meeting.

Sheena Aurora, MD, of lasmiditan's developer Eli Lilly, presented results from a pair of randomized phase III studies of lasmiditan.

SAMURAI and SPARTAN were randomized, double-blind trials comparing lasmiditan versus placebo for the treatment of acute migraine. Together, the studies included 4,439 participants. More than 80% were women, most were white, and the mean age was approximately 42 years. They had an average of about five migraines per month, one-third experienced aura, and they had moderate migraine-related disability (MIDAS score of 11 or higher). About 20% used prophylactic medications to reduce migraine frequency.

About 80% of patients had at least one risk factor for cardiovascular disease, including family history, smoking, hypertension, hyperlipidemia, and type 2 diabetes. SAMURAI, but not SPARTAN, excluded people with known coronary artery disease, arrhythmias, or uncontrolled hypertension.

In both studies, participants were randomly assigned to receive lasmiditan or placebo within 4 hours after the onset of migraine. Both studies evaluated oral doses of 100 mg and 200 mg, and SPARTAN also included a 50-mg dose. Patients could receive a randomized second dose, if needed, 2 to 24 hours after the first.

In both studies, patients experienced headache pain relief in as little as one hour, with better response rates seen at the higher doses, Aurora reported.

In SAMURAI, about 15% of people taking the 200-mg dose were pain-free at 1 hour after lasmiditan administration, rising to 32.2% at 2 hours in a modified intention-to-treat analysis. The same proportion in SPARTAN taking the highest dose were pain-free at 1 hour, rising to nearly 30% at 1.5 hours and 38.8% at 2 hours. Response rates in the placebo group at 2 hours were 15.3% and 21.3% in the two studies. Participants taking the 50-mg dose did not see a significant advantage over placebo until 2 hours post-administration.

The researchers also looked at relief of the most bothersome symptom as defined by the patient, most often photophobia. In both studies, about 25% of participants taking the highest dose reported being free of this symptom at 1 hour after administration, rising to 40.7% in SAMURAI and 48.7% in SPARTAN at 2 hours. Corresponding 2-hour rates in the placebo arms were 29.5% and 33.5%. Significant separation from the placebo was seen as early as half an hour in the high-dose lasmiditan arm.

Overall, SAMURAI participants reported about 60% headache pain relief and SPARTAN participants reported nearly 65% relief at 2 hours after the first dose of lasmiditan at either 100 mg or 200 mg. Placebo recipients reported about 40% pain relief in both studies.

Treatment with lasmiditan was generally safe and well tolerated. About 40% of patients receiving the 200-mg dose and 36% of those taking 100 mg experienced treatment-emergent adverse events, all mild to moderate. The most common side effects in the 200-mg arm were dizziness (16.3%-18.0%), paresthesia (6.6%-7.9%), somnolence (5.4%-6.5%), fatigue (3.1%-4.8%), and nausea (2.6%-5.3%). Less than 1% experienced cardiovascular adverse events.

An open-label trial called GLADIATOR is now underway to assess the longer-term safety and efficacy of lasmiditan, Aurora said.

Presentation session moderator Andrew Charles, MD, of the David Geffen School of Medicine at UCLA, told 番茄社区, "As a whole, we're seeing dramatic new approaches from multiple sources. My overall impression is that these are extraordinary times, with new approaches based on new delivery methods and modification of old approaches, but also new molecules."