2015 review of migraine research
We have all heard that there are limited funds for migraine research, a shortage of qualified doctors, and infrequent launches of new treatments. When was the last time you heard anything about what is actually being done to improve treatment for migraine patients? The really great news is that researchers are working hard on shoestring budgets, trying to find better ways to help us manage migraine. They haven’t given up, so neither should we.
Here is where we stand right now.
Sumatriptan intranasal — Avanir Pharmaceuticals, Inc.
This new intranasal delivery device for low-dose powdered sumatriptan, ran into problems when subjects had difficulty using the device properly during clinical trials. In late 2014, the FDA declined to approve Sumatriptan intranasal until the company assess the cause of these user errors. Avanir planned to provide new data in 2015, but was acquired by Otsuka Pharmaceutical Co. Ltd. Since the acquisition, no new information has been released. Hopefully they will finish the job in 2016.
Semprana® (inhaled DHE) – Allergan, Inc.
Allergan has been working on an inhaled version of DHE that has received three FDA denials. The company announced FDA approval would come in mid-2015, but there’s been no news. I doubt this one will be available any time soon, if ever.
Lasmiditan — CoLucid Pharmaceuticals, Inc.
Phase 3 Trial: A Study of Two Doses of Lasmiditan (100 mg and 200 mg) Compared to Placebo in the Acute Treatment of Migraine: A randomized, double-blind, placebo-controlled parallel group study
If it gains approval, this will be the first triptan without vasoconstriction. This would be a boon for patients who cannot tolerate the side effects of vasoconstriction or for whom it is contraindicated. The Phase 3 clinical trial will enroll over 2000 subjects who all have risk factors for cardiovascular disease (making them ineligible to use current triptans). The study is projected to be completed in mid-2016. Let’s keep our fingers crossed that this one gets to market very soon!
Topofen™ gel (ketoprofen) – Achelios Therapeutics
Phase 1B Trial: Study to Determine the Efficacy and Safety of ELS-M11 in Acute Migraine
This one caught my eye because I used to be able to get ketoprofen over-the-counter. It was my preferred abortive for years, working much better than Excedrin and almost as good as triptans. This topical ketoprofen gel can be applied to the skin over the 3 branches of the trigeminal nerve at the first sign of a migraine attack. So far, there has been one small Phase 1 trial with promising results. 45% were pain-free from 2-24 hours after application. 50% were pain-free after 24 hours. Unfortunately, there’s been no news about future trials.
Subcutaneous Histamine dihydrochloride – BioHealthonomics Inc.
Phase 2 Trial: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of Subcutaneous Histamine Dihydrochloride for Migraine Prophylaxis
In late 2013, filed an application with the FDA for a small human trial. Unfortunately, the study is still listed as “not yet recruiting.”
Intranasal Kinetic Oscillation Stimulation – Chordate Medical
Phase 2 Trial: A Randomized, Placebo-controlled, Double-blind, Multi-center Pilot Study to Evaluate the Prophylactic Effect and Tolerability of Intranasal Kinetic Oscillation Stimulation (KOS) Using the Chordate System S200 in Patients Diagnosed With Migraine
This study was scheduled for completion in 2015. We can expect trial results to be available sometime in 2016.
Intranasal Oxytocin (TI-001) – Trigemina, Inc.
Phase 2 Trial: TI-001 (Intranasal Oxytocin) for Treatment of Chronic Migraine
Study results are expected in early 2016.
Occipital Nerve Stimulation – Boston Scientific Corp.
Occipital Nerve Stimulation (ONS) for Migraine: OPTIMISE will evaluate the safety and efficacy of the ONS Precision System for the management of intractable migraine. Results are expected in June 2017.
Neuromodulation System – Scion NeuroStim
A Non-Invasive Neuromodulation Device for Treatment of Migraine Headache
This study is scheduled for completion soon, so watch for results late in 2016.
MLD10 (magnesium l-lactate dehydrate) – Pharmalyte Solutions, LLC
Phase 2/3 trial: MLD10 in the Prevention of Migraine in Adult
This study is scheduled for completion in late 2016 so results won’t be available until 2017.
MK 1602 (Small molecule CGRP antagonist) – Merck & Co. (acquired by Allergan)
Phase 2 trial is complete. Phase 3 study to begin soon. Watch for details coming later this year. This is the only oral CGRP antagonist currently in development.
LY2951742 (humanized CGRP antibody) – Eli Lilly and Co.
Phase 2B: Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients With Episodic Migraine
Results were reported in 2015 showing that this once-monthly injection safely reduced migraine headache days for episodic migraineurs. This confirmed previous study results. No word on the start of Phase 3 trials. However, Lilly has initiated two Phase 3 trials for episodic and chronic cluster headache. The FDA fast-tracked these trials based on the severity of cluster headache and the woeful lack of available treatments. If it succeeds, this will be the first preventive for cluster headache in history.
ALD403 (CGRP antibody) – Alder Biopharmaceuticals, Inc.
Phase 2B trial: A Parallel Group, Double-Blind, Randomized, Placebo Controlled, Dose-Ranging Phase 2 Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of ALD403 Administered Intravenously in Patients With Chronic Migraine
The study of this genetically engineered humanized CGRP antibody began in late 2014. News of the results are expected in early 2016. Alder also initiated a Phase 1 study to investigate quarterly self-administration of ALD403. Following announcement of the results (also in early 2016), a Phase 2B study will determine optimal dosing for episodic migraine patients. Alder also has a Phase 3 trial planned for high-frequency episodic migraine and one for chronic migraine.
TEV-48125 (humanized CGRP antibody) – Teva Pharmaceuticals
Phase 2 trial: A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, Parallel Group, Multi-Dose Study Comparing the Efficacy and Safety of Subcutaneous LBR-101 With Placebo for the Preventive Treatment of Chronic Migraine
Phase 2 trial: A Multicenter Assessment of TEV-48125 in High Frequency Episodic Migraine
TEV-48125 is a humanized monoclonal antihuman antibody that binds to CGRP, blocking its ability to interact with human CGRP receptors. The results of two Phase 2 trials published in 2015 generated a lot of excitement within the migraine community because 15% of the subjects treated with the drug experienced a full 12-week remission of migraine headache symptoms. 11% experienced a 75% reduction and 53% experienced at least a 50% reduction in migraine days. Even better, no serious side effects were reported. We’re still waiting for news about Teva’s plan for Phase 3 trials.
AMG 334 (fully human CGRP receptor antibody) – Amgen
Phase 2 trials:
A Phase 2 Study to Evaluate the Efficacy and Safety of AMG 334 in Migraine Prevention
A Study to Evaluate the Efficacy and Safety of AMG 334 in Chronic Migraine Prevention
Study to Assess the Long-term Safety and Efficacy of AMG 334 in Chronic Migraine Prevention
Phase 3 trial: Study to Evaluate the Efficacy and Safety of AMG 334 Compared to Placebo in Migraine Prevention
AMG 334 is a fully human monoclonal antibody that targets the CGRP receptors. Results from the Phase 2 trials are expected in 2016. We will have to wait until 2018 for results from the Phase 3 trial.
These are just the highlights.
According to the National Institutes of Health, there are over 622 clinical trials studying the mechanisms of migraine as well as drug and non-drug acute and preventive treatments. So the next time you start to feel discouraged, thinking that nobody is doing anything to help migraine, remember that there are scientists hard at work trying to ease the burden of migraine.
- gov, U.S. National Institutes of Health, retrieved 12/29/2015 online at https://clinicaltrials.gov/ct2/results?term=migraine&cond=%22Migraine+Disorders%22
- Peroutak, Stephen J. MD, PhD, (Nov. 2015), Clinical Trials Update 2015: Year in Review, Headache, 2015, Wiley Periodicals, Inc. soi: 10.1111/head.12744.