Lasmiditan for the treatment of migraine

Capi, Matilde; Andrés, Fernando de; Lionetto, Luana; Gentile, Giovanna; Cipolla, Fabiola; Negro, Andrea; Borro, Marina; Martelletti, Paolo; Curto, Martina

doi:10.1080/13543784.2017.1280457

Cited by 38 publications

(32 citation statements)

References 40 publications

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“…Lilly’s re‐acquired (from CoLucid Pharmaceutical) centrally acting serotonin 5‐HT 1F receptor selective agonist lasmiditan also lacks cardiovascular side effect liability and faces a similar challenge for differentiation from the triptans since its efficacy, as measured by pain‐free rates at 2 hours, is similar to the triptan class (28‐32% depending on the dose). Due to its central mechanism of action, lasmiditan use is associated with a higher rate of CNS adverse effects such as dizziness and sedation . It is unknown whether, due to its central site of action, lasmiditan will also carry a warning regarding CNS serotonin syndrome.…”

Section: Competitionmentioning

confidence: 99%

Calcitonin Gene‐Related Peptide Modulators – The History and Renaissance of a New Migraine Drug Class

2019

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Several lines of evidence pointed to an important role for CGRP in migraine. These included the anatomic colocalization of CGRP and its receptor in sensory fibers innervating pain‐producing meningeal blood vessels, its release by trigeminal stimulation, the observation of elevated CGRP in the cranial circulation during migraine with normalization concomitant with headache relief by sumatriptan, and translational studies with intravenous (IV) CGRP that evoked migraine only in migraineurs. The development of small molecule CGRP receptor antagonists (CGRP‐RAs) that showed clinical antimigraine efficacy acutely and prophylactically in randomized placebo‐controlled clinical trials subsequently gave definitive pharmacological proof of the importance of CGRP in migraine. More recently, CGRP target engagement imaging studies using a CGRP receptor PET ligand [11C]MK‐4232 demonstrated that there was no brain CGRP receptor occupancy at clinically effective antimigraine doses of telcagepant, a prototypic CGRP‐RA. Taken together, these data indicated that (1) the therapeutic site of action of the CGRP‐RAs was peripheral not central; (2) that IV CGRP had most likely evoked migraine through an action at sites outside the blood‐brain barrier; and (3) that migraine pain was therefore, at least in part, peripheral in origin. The evolution of CGRP migraine science gave impetus to the development of peripherally acting drugs that could modulate CGRP chronically to prevent frequent episodic and chronic migraine. Large molecule biologic antibody (mAb) approaches that are given subcutaneously to neutralize circulating CGRP peptide (fremanezumab, galcanezumab) or block CGRP receptors (erenumab) have shown consistent efficacy and tolerability in multicenter migraine prevention trials and are now approved for clinical use. Eptinezumab, a CGRP neutralizing antibody given IV, shows promise in late stage clinical development. Recently, orally administered next‐generation small molecule CGRP‐RAs have been shown to have safety and efficacy in acute treatment (ubrogepant and rimegepant) and prevention (atogepant) of migraine, giving additional CGRP‐based therapeutic options for migraine patients.

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Section: Competitionmentioning

confidence: 99%

Calcitonin Gene‐Related Peptide Modulators – The History and Renaissance of a New Migraine Drug Class

2019

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“…9 Although the introduction of triptans improved the acute treatment of migraine, this class of medication is not suitable for all patients with migraine. 12 Lasmiditan has high affinity and selectivity for 5-HT 1F receptors and lacks the vasoconstrictor activity inherent with triptans. 10 Lasmiditan (LY573144) is a novel therapeutic agent designated as a "ditan" in development for the acute treatment of migraine.…”

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confidence: 99%

Onset of Efficacy Following Oral Treatment With Lasmiditan for the Acute Treatment of Migraine: Integrated Results From 2 Randomized Double‐Blind Placebo‐Controlled Phase 3 Clinical Studies

et al. 2019

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Objective To expand on available information on the efficacy of oral lasmiditan for the acute treatment of migraine with particular focus on the timing of the effect and on its impact on migraine‐associated symptoms. Background Lasmiditan is a novel selective 5‐hydroxytryptamine 1F receptor agonist that lacks vasoconstrictive activity. In 2 phase 3 studies, SAMURAI and SPARTAN, lasmiditan met primary and key secondary efficacy endpoints at 2 hours following initial dose. Methods Integrated analyses were completed from 2 phase 3 clinical trials, SPARTAN and SAMURAI. Baseline data and data collected every 30 minutes up to 2 hours after taking lasmiditan (50, 100, or 200 mg) or placebo were analyzed to determine the onset of efficacy. A total of 5236 patients were randomized to be treated with placebo (N = 1493), lasmiditan 50 mg (N = 750), lasmiditan 100 mg (N = 1498), or lasmiditan 200 mg (N = 1495). Data were analyzed to determine the onset of improvement for the following efficacy measures: pain freedom, most bothersome symptom freedom, pain relief, freedom from associated individual symptoms (photophobia, phonophobia, or nausea), total migraine freedom (defined as pain freedom and freedom from associated symptoms), and freedom from migraine‐related functional disability. Time to meaningful headache relief and time to first become pain free were also analyzed. Results Significantly higher rates of pain freedom (100 mg, 10.0%, P = .012; 200 mg, 15.5%, P < .001; Placebo, 7.0%) and total migraine freedom (100 mg, 8.9%, P = .017; 200 mg, 12.4%, P < .001; Placebo, 6.1%) were achieved starting at 60 minutes in 100‐ and 200‐mg lasmiditan‐treated groups compared with placebo group. Rates of freedom from most bothersome symptom (100 mg, 11.1%, P = .015; 200 mg, 13.0%, P < .001; Placebo, 7.9%), and pain relief (100 mg, 17.5%, P = .007; 200 mg, 19.1%, P < .001; Placebo, 13.4%) were significantly higher starting as early as 30 minutes in lasmiditan 100‐ and 200‐mg lasmiditan‐treated groups. A significantly higher percentage of patients in the 200‐mg lasmiditan‐treated group achieved freedom from photophobia (13.7%, P = .005; Placebo, 9.2%) and phonophobia (17.4%, P = .042; Placebo, 13.4%) starting at 30 minutes. A significantly greater proportion of patients in the 200‐mg lasmiditan‐treated group achieved freedom from migraine‐related functional disability starting at 60 minutes (16.4%, P < .001; Placebo, 11.1%). All efficacy measures, except for freedom from nausea, were statistically significant after lasmiditan treatment (50, 100, or 200 mg) compared with placebo at 90 and 120 minutes. Finally, patients taking lasmiditan had a higher likelihood of achieving meaningful headache relief and becoming headache pain free within 24 hours compared with those taking placebo (P < .001). Conclusions Patients treated with lasmiditan for a migraine attack reported an earlier onset of efficacy compared with those treated with placebo. Some of the efficacy measures such as pain relief demonstrated improvement as early as the first asse...

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“…In the development pipeline of new drugs for the acute treatment, there is only one innovative compound, lasmiditan [4], while there are numerous devices and nutraceuticals in both categories [5]. This is surely not the scenario that one billion of migraine patients is hoping for from scientific research, and a new call for action is required in order to promote the study on new innovative drugs for the acute treatment of migraine.…”

Section: Introductionmentioning

confidence: 99%

“…From the mechanism of action point of view, lasmiditan efficacy in migraine is mediated through a nonvascular, first neural pathway, with a loss of the typical vasoconstrictor activity expressed by triptans [4].…”

Section: Preventative Treatment Is Now Moving Forwardmentioning

confidence: 99%