Profiling lasmiditan as a treatment option for migraine

ABSTRACT

Introduction: In recent years, research into acute migraine treatment has aimed to develop molecules capable of inhibiting trigeminal pathways, mediated by agonism to 5-HT1F receptors in order to avoid the vasoconstrictive action due to the stimulation of 5-HT 1B/1D receptors. A novel migraine drug class, called ‘neurally acting anti-migraine agents’, has been developed for the management of acute migraine attacks. Lasmiditan is the only compound of this drug class that has been evaluated in Phase III clinical trials.

Areas covered: This review discusses lasmiditan including its pharmacokinetics, pharmacodynamics, efficacy and safety profile. Original research and review articles, relative to the period 2010–2019, were included in the reviewed literature.

Expert opinion: The most recent phase III trials have demonstrated the efficacy of lasmiditan for acute migraine treatment, even if compared only with placebo. Nevertheless, the low rate of cardiovascular side effects with lasmiditan might offer a potential therapeutic option for migraine patients with cardiovascular disorders. With the lack of data on lasmiditan’s pharmacokinetic features, several phase I clinical trials are still ongoing in order to evaluate half-life, metabolism, excretion and the potential production of active metabolites. Possible pharmacodynamic interaction with drugs acting on central nervous system should be evaluated in future studies.

KEYWORDS:

• Lasmiditan
• NAAMA
• migraine
• ditans
• pain
• 5HT1F agonist
• acute migraine drug

Article highlights

• Migraine is a neurological and disabling diseases with a global prevalence of 12%.

• Pharmacological intervention for acute migraine attack includes triptans and NSAIDs.

• Triptans act as 5-HT1b/d receptors agonism but their use is contraindicated in patients with CVDs for the vasoconstrictive action.

• Ditans present an acute antimigraine activity via 5-HT1freceptor agonism without vasoconstrictive action.

• Lasmitidan is the first compound of this class hat has been evaluated in Phase III RCTs.

• Lasmitidan showed to be superior to placebo in acute migraine treatment.

• Lasmitidan should be tested in future RCTs comparative studies with triptans and NSAIDs.

• Lasmitidan should be tested in future RCTs in migraine patients with CVDs and psychiatric comorbidity to confirm the drug broad safety.

Declaration of interest

P Martelletti has received personal fees for advisory board participation as well as research and educational grants via the University Department from Allergan, Eli Lilly and Company, Novartis and Teva Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work has been supported by The Italian Foundation for the Study of Headaches – ONLUS.