MAP Pharmaceuticals submits LEVADEX NDA to FDA for treatment of migraine in adults

MAP Pharmaceuticals, Inc. (Nasdaq: MAPP) today announced that it has submitted a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for LEVADEX® orally inhaled migraine drug for the potential acute treatment of migraine in adults. According to the National Headache Foundation, approximately 30 million people in the United States suffer from migraine, a debilitating neurological disorder. Common symptoms of migraine include recurrent headaches, nausea, phonophobia (sensitivity to sound) and photophobia (sensitivity to light).

"This NDA submission marks a major corporate milestone for MAP Pharmaceuticals and brings us one step closer to our goal of providing the underserved migraine patient population with a potential new treatment option," said Timothy S. Nelson, president and chief executive officer of MAP Pharmaceuticals. "Our comprehensive development program evaluated LEVADEX in approximately 1,000 patients for up to one year, treating nearly 10,000 migraines. If approved by the FDA, LEVADEX could potentially provide a new treatment option for migraine sufferers, including the millions of patients whose migraines are not well treated today."

The 505(b)(2) NDA submission is based on a comprehensive development program for LEVADEX, and includes efficacy and safety data from the Phase 3 FREEDOM-301 clinical trial that has been presented at scientific conferences and was recently published in Headache: The Journal of Head and Face Pain. In the FREEDOM-301 trial, patients self-administered LEVADEX at home using the Company's proprietary TEMPO® inhaler. LEVADEX contains a novel formulation of dihydroergotamine (DHE).  Patients taking LEVADEX in this pivotal trial had statistically significant improvement at two hours compared to patients on placebo for all four co-primary endpoints:

• Pain relief: 58.7 percent of patients who received LEVADEX compared with 34.5 percent for placebo (p<0.0001);
• Phonophobia free: 52.9 percent of patients who received LEVADEX compared with 33.8 percent for placebo (p<0.0001);
• Photophobia free: 46.6 percent of patients who received LEVADEX compared with 27.2 percent for placebo (p<0.0001); and
• Nausea free: 67.1 percent of patients who received LEVADEX compared with 58.7 percent for placebo.

The most common adverse event reported in the double-blind placebo controlled portion of the trial was medication aftertaste at six percent versus two percent for placebo.  The next most common adverse event reported was nausea at five percent compared with two percent for placebo.  There were no differences in changes in lung function, as measured by spirometry, between the active and placebo groups. 

The 12 month open-label, safety extension of the Phase 3 FREEDOM-301 trial was designed to evaluate overall safety of LEVADEX over six and 12 months of exposure.  In total, more than 475 patients completed six months treatment and more than 250 patients completed 12 months treatment.  There were no drug related serious adverse events reported in any LEVADEX trial.  

The NDA submission also includes data from a pharmacokinetics (PK) trial evaluating the PK and safety of LEVADEX in smokers and non-smokers, a pharmacodynamics (PD) trial evaluating the acute effects of LEVADEX on pulmonary artery pressure, a thorough QT trial comparing the acute effects of a supra-therapeutic dose of LEVADEX on the cardiac QT interval as measured by electrocardiogram and a safety trial in adult asthmatics.

• Systemic exposure to LEVADEX was not higher in smokers, potentially due to reduced pulmonary absorption, in the PK study comparing smokers vs. non-smokers.
• There was no difference in pulmonary arterial systolic pressure between the LEVADEX and the placebo group over two hours in the PD study.
• Results of the QT trial showed that a supra-therapeutic dose of LEVADEX does not increase QTc intervals.  
• PK concentrations for LEVADEX in asthmatics were similar to those in healthy subjects.

SOURCE MAP Pharmaceuticals, Inc.