Levadex migraine spray shows promising results says Map Pharma

Levadex, a new orally inhaled drug to treat migraine, is currently in final stages of human studies.

Levadex uses a novel formulation of dihydroergotamine (DHE), a drug used intravenously in clinical settings to effectively and safely treat migraines.

Developed by Map Pharmaceuticals, Levadex showed that it provided rapid and sustained pain relief in migraine sufferers for up to 48 hour after dosing. 

Patients taking Levadex had statistically significant improvement at two hours compared to patients on placebo.

The Phase III programme with Levadex analysed data from a total of 792 patients as specified in the protocol of the FREEDOM-301 study, which was conducted under a Special Protocol Assessment agreement with the US Food and Drug Administration (FDA). 

The patient population studied had more severe migraine pain than expected, with 46 percent reporting severe pain and 54 percent reporting moderate pain prior to administration of the study drug.

Levadex therapy achieved statistically significant onset of pain relief at 30 minutes after dosing. Of the sample population, 50% more of the patients receiving Levadex therapy, than the patients receiving placebo, reported pain relief at 10 minutes.

Levadex study reported no serious drug-related adverse events in the trial.  Levadex was well tolerated, with the most common adverse event reported being medication aftertaste at six percent, with two percent of patients receiving placebo also reporting medication aftertaste.

Nausea was the next most common adverse event with Levadex at five percent, compared with two percent for placebo. Symptoms or sensitivities typically associated with commonly used triptan migraine treatments, such as chest discomfort (one percent) or chest pain (0 percent), were rare and comparable to placebo.

There were no changes in lung function, as measured by spirometry, between the active and placebo groups.

“These results show the potential of Levadex to provide both rapid and sustained relief of all migraine symptoms to patients who suffer from migraine,” said Sheena Aurora, MD, a FREEDOM-301 clinical study investigator, director of the Swedish Headache Center and assistant professor of neurology at the University of Washington School of Medicine. 

She said that migraines were painful and could be incapacitating, with current treatments serving only a minority of migraine sufferers.

“Patients continue to seek new migraine therapies that offer both fast and long-lasting relief from pain and migraine associated symptoms so that they can resume daily activities as quickly as possible. Levadex has the potential to address this unmet need and to be a first-line therapy for migraine,” she added.

Migraine is a common, debilitating neurological disorder that affects approximately 30 million people in the United States, according to the National Headache Foundation.

Limitations of oral triptans, the class of prescription drugs widely used for migraines, include slow onset of significant pain relief between 45 and 90 minutes, substantial variability in patient response and side effects such as heightened blood pressure.

“Market research has shown that migraine patients want medications that can treat all symptoms of their migraine rapidly and that are long-lasting as well as convenient to take,’’ said Timothy S Nelson, president and chief executive officer of MAP Pharmaceuticals. 

Compared to currently available migraine therapies, Map believed that Levadex has the potential to address all these patient needs and to offer a significant advancement in migraine therapy for this underserved patient population, he added.

Patients administer Levadex themselves using the company’s proprietary Tempo inhaler. Levadex is designed to incorporate the multiple beneficial mechanisms of action that allow DHE to block initiation of migraine, limit pain, reduce inflammation and stop a migraine at any point in the migraine cycle. 

Map plans to present further data from this trial at an upcoming medical conference.

What is migraine?

Common symptoms of migraine include recurrent headaches, nausea, vomiting, photophobia (sensitivity to light) and phonophobia (sensitivity to sound). 

According to the National Headache Foundation, most migraines last between four and 24 hours, but some last as long as three days.

On an average, migraine sufferers experience 1.5 migraine attacks monthly, although 25 percent of them experience one or more attacks weekly, according to published studies. 

Migraine patients report that currently approved drugs do not fully meet their needs due to slow onset of action, short duration of effect, inconsistent response and unacceptable side effect profiles.

The economic burden of migraine remains substantial despite existing treatments, with the direct and indirect costs of migraine in the United States estimated at over $20 billion annually.

FREEDOM-301 Trial

FREEDOM-301, the first Phase 3 study of Levadex therapy, was conducted under a Special Protocol Assessment with the US Food and Drug Administration.

FREEDOM-301 is a multi-center, randomized, double-blind, placebo-controlled trial. 

The study is designed to evaluate the safety and efficacy of Levadex as a potential treatment for acute migraine. Primary efficacy measures include pain relief, and being phonophobia, photophobia and nausea free at two hours after dosing.

A total of 792 patients (ages 18 to 65) were included in the modified intent to treat population used for primary data analysis, as specified in the protocol.

Patients enrolled in the trial were evaluated for the treatment of a single moderate or severe migraine, and then were given the option to continue in an open label, long-term safety arm.

This safety arm is targeting 300 patients for six months and 150 patients for 12 months, and over 500 patients are continuing in this arm of the trial.

MAP Pharmaceuticals Inc is based in Mountain View, CA. Map has two product candidates in Phase 3 clinical development.

Unit Dose Budesonide is being developed in collaboration with AstraZeneca for the potential treatment of asthma in children, and Levadex inhaled therapy is being developed for the potential treatment of migraine.

In addition, MAP Pharmaceuticals develops new therapies by applying its proprietary drug particle and inhalation technologies to enhance the therapeutic benefits of proven drugs.