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New Medicines

ReyvowMigraine - acute treatment

Information

Reyvow
New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Launched
Nov 20Filed in EU via centralised procedure [19].
Feb 20The US Institute for Clinical and Economic Reviews (ICER) final report on lasmiditan, ubrogepant and rimegepant concludes rimegepant and ubrogepant are cost effective at commonly used thresholds for patients for whom triptans are not effective, not tolerated, or are contraindicated, but that lasmiditan exceeds the $150,000 per QALY gained threshold in this population. For patients able to take triptans, sumatriptan and eletriptan are both more effective and less expensive than these newer agents [17].
Jan 20Launched in the US with a list price of $4,610 per year [15,16].
Oct 19Approved in the US [13]
Nov 18Filed in US for acute treatment of migraine with or without aura in adults [11].
Jan 17Eli Lilly will spend nearly $1 billion to buy out CoLucid Pharmaceuticals and get rights to lasmiditan, which Lilly outlicensed to the company back in 2005. A data readout for the SPARTAN study is expected in H2 2017. If this trial is positive, US filing could occur in 2018 [9].
Sep 16CoLucid has announced that lasmiditan achieved both primary and key secondary endpoints in the pivotal PIII SAMURAI study with statistical significance (p<0.001); the second pivotal study (SPARTAN) is on-going [7].
Mar 12CoLucid intends to advance oral lasmiditan into a pivotal PIII trial in the US in 2012. The trial will enrol pts with acute migraine, with or without aura. The company expects the trial to confirm that lasmiditan´s tolerability profile is highly differentiated from triptans & ergotamines [3].

Category

Member of a novel chemical class known as ditans which penetrates the central nervous system (CNS) and selectively targets 5‑HT1F receptors expressed in the trigeminal nerve pathway.
Migraine affects about 6% of men and 18% of women.
Migraine - acute treatment
Oral

Further information

Yes

Trial or other data

Nov 20The US Institute for Clinical and Economic Reviews (ICER) final report on lasmiditan, ubrogepant and rimegepant concludes rimegepant and ubrogepant are cost effective at commonly used thresholds for patients for whom triptans are not effective, not tolerated, or are contraindicated, but that lasmiditan exceeds the $150,000 per QALY gained threshold in this population. For patients able to take triptans, sumatriptan and eletriptan are both more effective and less expensive than these newer agents [17].
Nov 20If approved lasmiditan would be a good pairing for Lillys other big migraine hope galcanezumab, a CGRP inhibitor which, rather than treating acute attacks, works as a maintenance therapy to try to stop them occurring in the first place. Lilly is competing with rivals Teva and Alder Biopharma to bring the first CGRP inhibitor to market [10]. Patients with cardiovascular disease are poor candidates for triptans, and the PIII trials of lasmiditan have emphasised this patient population. If the trials confirm efficacy and safety in this patient group, the drug will fill a significant unmet need in the treatment of migraine. Orally-active CGRP antagonists are being developed for both acute treatment and prophylaxis of migraine. If successful, those for acute migraine will provide the first specific alternative to triptans; those for prophylaxis are likely to provide strong competition to the monoclonal CRGP antagonists.
Jan 19GLADIATOR Phase III open-label study is active but not recruiting. It is estimated that the study will complete in September 2019. [12]
Aug 17Top-line results of the SPARTAN trial show that lasmiditan provided relief from the headache pain and other symptoms associated with acute migraine attack, such as nausea and aversion to light or loud sounds, in as little as two hours, matching the results of its earlier SAMURAI study. With a dose of 50mg, 28.6% of patients were headache-free at two hours, rising to 31.4% at the 100mg dose and 38.8% of those on 200mg. The placebo response rate was 21.3%. Upwards of 40% of patients in all three dose groups were also free of their most bothersome symptom other than headache, compared to a third (33.5%) of the placebo group [10].
Jan 17NCT02565186 (GLADIATOR) is a PIII open-label study in 2580 subjects who have completed SAMURAI and SPARTAN studies, to evaluate the safety and tolerability of long-term intermittent use of lasmiditan 100mg and 200mg as the first dose and as a second rescue dose, for the acute treatment of migraine. The study is due to complete May 18 [8].
Sep 16Lasmiditan achieved both primary and key secondary endpoints in the SAMURAI study with statistical significance (p<0.001) and good tolerance. The study (NCT02439320, n=2231) compared lasmiditan 100 mg and 200 mg to matching placebo in patients with severe disability from acute migraine (mean Migraine Disability Assessment score of 31); 82% of participants had multiple cardiovascular risk factors and would therefore be poor candidates for triptan treatment. The on-going SPARTAN study is currently recruiting in the US, with expansion to the UK and Germany expected [7].
Dec 15NCT02605174 (SPARTAN) is a PIII study of three doses of lasmiditan (50, 100 and 200mg) vs placebo in the acute treatment of migraine in 2968 subjects. The study will start Apr 16 and is due to complete Aug 17 [6].
Nov 1550% of enrollment into the PIII, SAMURAI trial (n=2,225) complete. CoLucid Pharma expects to have the trial fully enrolled in the 1st half of 2016 [5].
Mar 15The PIII Samurai study (A Study of Two Doses of LAsMiditan (100mg and 200mg) Compared to Placebo in the AcUte Treatment of MigRAIne) has started with data expected 3Q 2016. The study will recruit 2,225 patients including those with CV risk and some forms of stable CV disease. The primary endpoint is the proportion of patients headache pain free at two hours. The second pivotal study COL MIG-302 is planned to start 2H 2915 with data expected 2H 2017. Both studies have an SPA agreed with the FDA. An open label long-term study (COL MIG-305) is also planned [5].
Sep 12In a QT/QTc study lasmiditan caused no significant QT prolongation either at 100mg (the putative therapeutic dose) or at 400mg (supratherapeutic dose), whereas moxifloxacin caused a QT prolonging effect similar to that seen in published studies. No pro-arrhythmic effect of lasmiditan was observed in the assessments of ECGs made by a cardiologist [4].
Mar 12NCT00883051 recruited pts in France, Belgium, Spain, Finland & Germany [2].
Mar 12Results of a large European dose-ranging study (NCT00883051) published early online in Lancet Neurology. A total of 512 pts with migraine (± aura) who were not using prophylaxis & who were seen at one of 43 headache centres in five EU countries were randomised to double-blind treatment with lasmiditan (50mg, 100mg, 200mg, or 400mg; n=305) or placebo (n=86), to be taken by the pt at home to treat one moderate or severe attack. The primary endpoint was dose response for headache relief (moderate or severe becoming mild or none) at 2 hrs. There was a linear association between headache response rate at 2 hrs & lasmiditan dose (p<0.0001). Every lasmiditan treatment dose significantly improved headache response at 2 hrs vs. placebo (lasmiditan 50mg: difference 17.9% [95% CI 3.9-32.1]; p=0.022; 100mg: 38.2% [24.1-52.4]; p<0.0001; 200mg: 28.8% [9.6-39.9]; p=0.0018; 400mg: 38.7% [23.9-53.6]; p<0.0001). The proportion of pts with treatment-emergent adverse events increased with increasing doses (from 65% with 50mg to 84% with 400mg, vs. 22% with placebo). Severe adverse events were reported by 20%, 28%, 39%, & 44% of patients on lasmiditan 50, 100, 200, & 400mg, respectively, vs. 6% on placebo. The most common adverse events were CNS related & included dizziness, fatigue, vertigo, paraesthesia, & somnolence [1].

Evidence based evaluations