Assistant

A week after moving its inhaled pediatric asthma drug into Phase III testing, MAP Pharmaceuticals unveiled its upcoming Phase III program for MAP0004, an inhaled version of dihydroergotamine (DHE), in migraine.

The Mountain View, Calif.-based firm and the FDA recently reached agreement on a special protocol assessment for the first of two Phase III trials of MAP0004, which is set to begin early this year. It's designed to enroll about 850 patients who will be randomized to receive the drug or placebo to treat a single acute attack of migraine, with the primary endpoint defined by pain relief at two hours, along with relief from other migraine symptoms - nausea, photophobia and phonophobia - at two hours.

"We'll be collecting data on all four of those endpoints," plus a composite endpoint, said Timothy Nelson, MAP's president and CEO. "The goal is to have efficacy data near the end of this year."

Following the efficacy portion of the study, patients will continue in a 12-month open-label phase to provide long-term safety data. Those data, along with results from a planned confirmatory Phase III study, will serve as the basis for regulatory filing. Nelson said MAP will seek approval under the FDA's 505(b)(2) process.

MAP0004 is designed to be self-administered using the company's metered-dose Tempo inhaler, and results to date suggest that it could become a first-line migraine therapy. Phase II data showed that the product provided pain relief within 10 minutes of dosing and provides sustained relief through at least 24 hours, Nelson said.

That gives MAP0004 a clear advantage over oral triptans, the most widely prescribed migraine therapy. Though oral triptan sales topped $2 billion in 2006, Nelson said only a small percentage of the estimated 30 million migraine sufferers in the U.S. take triptans, and even in cases in which triptans are effective, patients must wait for the effects to kick in.

"You take a pill and then you have to go lie down in a dark room," often for between 45 minutes and 90 minutes before the triptans begin alleviating the pain and other migraine symptoms, he said.

MAP0004 is a formulation of DHE, a drug that is administered by intravenous injection and works very well in treating the symptoms of migraines. "But it's very unstable," Nelson told BioWorld Today. "So we figured out how to make it stable," and then formulated it as an inhalable product.

Patients can keep the inhaler close at hand - in a desk drawer, for example - and simply "take a puff on the inhaler" when they feel a migraine coming on, he added. "This is a product that has fast onset and sustained relief."

MAP0004 is one of two MAP programs to reach Phase III testing this year. Last week, the company began a Phase III trial of Unit Dose Budesonide (UDB), a nebulized formulation of the corticosteroid budesonide in pediatric asthma. That study is expected to enroll about 360 children, from as young as 12 months to 8 years, who will be randomized to receive one of two doses of UDB or placebo twice daily for 12 weeks. The primary endpoint will be measured by the change in nighttime and daytime composite symptom scores, evaluating coughing, wheezing and breathlessness.

Both pivotal programs are being funded solely by MAP. The firm had $45.5 million in cash, cash equivalents and short-term investments as of Sept. 30, and added another $62 million in net proceeds in October, when it priced an initial public offering of 5.8 million shares priced at $12 each. (See BioWorld Today, Oct. 8, 2007.)

"Those funds should get us through" the Phase III studies of MAP0004 and UDB, Nelson said. At that time, he added, the firm might look at potential partnerships or other options, "but we don't plan to do any more money raising" prior to getting a look at Phase III data.

Since both drugs are targeted to fairly specific markets, MAP intends to build its own sales force, though in the migraine space the firm likely will look at adding distribution or marketing partners down the road to expand the product's penetration, Nelson said.

Nelson, who joined the company in 2005, added, "We've been fortunate over the last three years to go from a preclinical-stage firm to one that's moving two programs into Phase III."

Earlier in the pipeline, MAP is developing MAP0005, a combination corticosteroid and long-acting beta2 agonist product designed to be delivered using the Tempo inhaler. That product was designed to provide the right ratio of components "at the micron particle level" to make each receptor gets the right mix, Nelson said.

A Phase IIa trial started in the fall in asthma and chronic obstructive pulmonary disease, and the firm expects "to share data later in 2008," he said.

The company has a fourth product in early clinical development that aims to deliver proteins and peptides in an inhalable product without requiring refrigeration.

Shares of MAP (NASDAQ:MAPP) gained $1.01, or 7.2 percent, Wednesday to close at $15.