The discovery and development of inhaled therapeutics for migraine

ABSTRACT

Introduction: Migraine is a disabling primary headache disorder that requires effective treatments. Inhalation is currently being explored for the delivery of drugs for migraine. Pulmonary-route delivery of drugs shows potential advantages for its use as a treatment, particularly compared the oral route.

Areas covered: The authors highlight the current state of the literature and review multiple therapies for migraine-utilizing inhalation as the route of administration. The following therapeutics are discussed: inhaled ergotamine, inhaled dihydroergotamine mesylate (MAP0004), inhaled prochlorperazine, and inhaled loxapine. Coverage is also given to normobaric oxygen, hyperbaric oxygen, and nitrous oxide therapies.

Expert opinion: Inhalation of MAP0004 showed promising results in terms of efficacy for acute migraine treatment in phase 3 studies, together with a more favorable tolerability profile compared to parenteral dosing and a better pharmacokinetic profile versus oral or intranasal delivery. In phase 2 trials, inhaled prochlorperazine shows good pharmacokinetics and efficacy, in contrast to inhaled loxapine that did not provide encouraging results in terms of efficacy. The authors see the potential for the use of dihydroergotamine mesylate in clinical practice pending regulatory approval.

KEYWORDS:

• Migraine
• inhalation
• therapies
• clinical trials

Article highlights

• There is still an unmet need for effective treatment of migraine, a disorder characterized by disabling and painful attacks of headache and associated symptoms.

• The use of inhalation therapies is a new field in the treatment of migraine and has been explored with multiple drugs.

• Inhaled DHE mesylate is a promising alternative to other routes administration and brings a better safety and tolerability profile with good efficacy for the treatment of migraine attacks.

• Inhaled neuroleptics such as prochlorperazine an loxapine have been researched but have so far not provided clear beneficial effects after phase 2 trials.

• It is our opinion that the field of inhalational therapies should be explored further for new treatments in migraine given the potential for ease of administration, efficacy, safety, and tolerability.

This box summarizes key points contained in the article.

Declaration of interest

N Vandenbussche reports receiving travel grants and educational grants from Allergan while PJ Goadsby reports grants and personal fees from Amgen Inc and Eli Lilly and Company as well as personal fees from Alder Biopharmaceuticals, Allergan, Autonomic Technologies Inc., Biohaven Pharmaceuticals Inc., Electrocore LLC, eNeura, Impel Neuropharma, MundiPharma, Novartis, Teva Pharmaceuticals, and Trigemina Inc in addition to WL Gore and Associates. PJ Goadsby further declares personal fees from MedicoLegal work, from the Massachusetts Medical Society, Up-to-Date, Oxford University Press, and Wolters Kluwer in addition to a patent on Magnetic stimulation for headache assigned to eNeura without fee. 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 manuscript has not been funded.