Effect of a rescue or recurrence dose of lasmiditan on efficacy and safety in the acute treatment of migraine: findings from the phase 3 trials (SAMURAI and SPARTAN)

Abstract

Background We studied the efficacy and safety of a second dose of lasmiditan for acute treatment of migraine. Methods SAMURAI and SPARTAN were double-blind, placebo-controlled Phase 3 studies in which individuals with migraine were randomized to oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo. Study drug was to be taken within 4 h (h) of onset of a migraine attack (moderate or severe pain). A second dose of study drug was provided for rescue (patient not pain-free at 2 h and took a second dose 2-24 h post-first dose) or recurrence (patient pain-free at 2 h, but experienced recurrence of mild, moderate, or severe migraine pain and took a second dose 2-24 h after first dose). Randomization to second dose occurred at baseline; patients originally assigned lasmiditan were randomized to the same lasmiditan dose or placebo (2:1 ratio), and those originally assigned placebo received placebo. Data from SAMURAI and SPARTAN were pooled for efficacy and safety assessment of a second dose of lasmiditan. Results The proportion of patients taking a second dose was lower with lasmiditan versus placebo, and decreased with increasing lasmiditan dose; the majority who took a second dose did so for rescue. In patients taking lasmiditan as first dose, outcomes (pain free, most bothersome symptom [MBS] free) at 2 h after a second dose for rescue were similar whether the second dose was lasmiditan or placebo ( p > 0.05 in all cases). In patients taking lasmiditan for first dose, outcomes at 2 h after a second dose for recurrence were as follows: lasmiditan pooled versus placebo - pain free, 50% vs 32% ( p > 0.05); MBS free, 71% vs 41% ( p = 0.02); pain relief, 77% vs 52% ( p = 0.03). In patients whose first dose was lasmiditan, the incidence of treatment emergent adverse events (TEAEs) reported after the second dose was similar whether second dose was lasmiditan or placebo. Conclusions A second dose of lasmiditan showed some evidence of efficacy when taken for headache recurrence. There was no clear benefit of a second dose of lasmiditan for rescue treatment. The incidences of TEAEs were similar whether the second dose was lasmiditan or placebo. Trial registration SAMURAI ( NCT02439320 ) [April 2015]. SPARTAN ( NCT02605174 ) [May 2016].

The potential of lasmiditan in migraine

“…The proportion of patients taking a second dose was lower with lasmiditan than with placebo and decreased with a higher lasmiditan dose. 32 A second dose of lasmiditan showed some evidence of efficacy versus placebo when taken for headache recurrence for freedom of the most bothersome symptom (71% versus 41%, p = 0.02) and pain relief (77% versus 52%, p = 0.03), but in pain freedom (50% versus 32%, p > 0.05) there was no significant difference. 32 There was also no clear benefit of a second dose of lasmiditan as a rescue treatment.…”

Lasmiditan: Its Development and Potential Use

“…Lasmiditan has a half‐life of approximately 6 hours and is recommended for only once‐daily dosing, as a second lasmiditan rescue dose when migraine continued at 2 to 24 hours was not more helpful that placebo. There was a subgroup of good lasmiditan responders (to the first dose) that did have some benefit from a second rescue dose . Conversely, lasmiditan (50‐200 mg) did offer some migraine relief 24 to 48 hours after the initial dose, compared to placebo, reaching statistical significance ( P values of <.01) for multiple classic migraine outcomes .…”

“…There was a subgroup of good lasmiditan responders (to the first dose) that did have some benefit from a second rescue dose. 13 Conversely, lasmiditan (50-200 mg) did offer some migraine relief 24 to 48 hours after the initial dose, compared to placebo, reaching statistical significance (P values of <.01) for multiple classic migraine outcomes. 14 With respect to concomitant prophylaxis migraine medication (antiepiletpic medications, antidepressants, beta blockers, etc), their use does not appear to affect lasmiditan efficacy and safety.…”

Novel acute therapies in the treatment of migraine: impact of re-dosing on cost–utility outcomes

“…1 Novel therapies include the calcitonin gene-related peptide (CGRP) receptor antagonists rimegepant (NURTEC ODT, Biohaven) 2 and ubrogepant (UBRELVY, Allergan) 3,4 and the 5HT-receptor agonist lasmiditan (REYVOW, Eli Lilly). 5 The design of pivotal trials for these therapies include a key difference, in that the rimegpant Phase III program only allowed for a single dose of study medication, while ubrogepant and lasmiditan trials both allowed for re-dosing: for ubrogepant, 37.6% of patients received a second dose (ACHIEVE) 3 and for lasmiditan 33% of patients required re-dosing (SAMURAI and SPARTAN). 5 The Institute for Clinical and Economic Research (ICER) conducted an evidence review in acute treatment for migraine, including network meta-analysis (NMA) and economic evaluation of…”

“…There is a significant amount of uncertainty regarding base case estimates regarding the impacts of therapies on pain relief more than 2 hours after treatment, on emergency room visits and hospitalizations, and the impact of re-treatment on migraine frequency. 1 With respect to lasmiditan re-dosing, the SAMURAI and SPARTAN trials both allowed for redosing in the first 24 hours, 5 and it is this re-dosing that is used to adjust medication cost in the revised analysis. However, the current product label for lasmiditan explicitly warns to not redose within 24 hours.…”