Medical Device Daily

Anyone who has ever used a standard meter dose inhaler — most commonly prescribed for asthma but more recently being used to treat other diseases, including diabetes — is familiar with the difficulty of trying to pump the drug canister and breathe in at the same time. Even after coordinating the actuation and inhalation as accurately as possible, the patient often feels the puff strike the back of their throat, making them wonder how much of the drug actually reached their lungs as intended.

To simplify inhaler use and ensure dosing consistency, MAP Pharmaceuticals (Mountain View, California) designed the Tempo inhaler, which incorporates a standard meter dose inhaler medication canister with a synchronized trigger and flow control chamber.

Timothy Nelson, CEO of Map Pharmaceuticals, told Medical Device Daily the Tempo inhaler is breath-synchronized so all the patient has to do is put it to their mouth and breathe – the device does the rest.

“The device doesn’t care how you breathe or how I breathe,” Nelson said.

Nelson also told MDD that one spray from the Tempo inhaler is capable of delivering three times as much of the drug down into the lung than with a standard inhaler.

“It’s getting where it needs to go,” Nelson said.

According to a Tempo demonstration video on the company’s web site, the patient simply raises the mouthpiece cover and inhales naturally. The airflow, created by the patient’s inhalation, draws air into the venturi, which signals the synchronized trigger to automatically discharge drug from the canister. As the medicine plume is released from the canister valve it collides with the air from the impinging jet, creating a mushroom effect. Once it reaches the front of the chamber, the drug plume has been slowed to less than one-tenth of the velocity at discharge from the valve. At the same time the particle size of the drug droplets have been reduced. This slower-moving plume of small drug particles is easily entrained in the patient’s respiratory breath and delivered past the mouth and throat into the lungs resulting in less drug delivery in the mouth and far more drug delivered to the lung, according to the video.

MAP is developing a series of inhaled respiratory and systemic drug products delivered with the Tempo inhaler. Though the company’s product portfolio includes drug candidates for the treatment of asthma, chronic obstructive pulmonary disease (COPD), and diabetes, its lead product is a systemic migraine treatment designed to provide faster and more consistent relief than current therapeutics.

The company reported yesterday that its Tempo Migraine drug candidate met its primary endpoints in a Phase II clinical program consisting of two separate trials. The drug is an orally inhaled form of dihydroergotamine (DHE) for the treatment of acute migraine.

Nelson said DHE has been used for 50 years as a rescue medicine for migraine sufferers who have to go to the emergency room and get the drug intravenously because nothing else has worked.

According to the company, the first Phase II study demonstrated clinically significant results in a randomized, outpatient, placebo-controlled study at nine U.S. headache centers. In addition, a second Phase II clinical trial indicated that Tempo Migraine was well tolerated by subjects with impaired pulmonary function.

In the first Phase II study, Tempo Migraine showed statistically significant pain relief at two hours and sustained pain relief at 24 hours compared to placebo in the treatment received population, according to MAP. In addition, Tempo Migraine demonstrated statistically significant pain relief at 10 minutes.

Nelson said the possibility of providing pain relief to migraine sufferers in 10 minutes — without them having to go to the emergency room and receive an IV — is “tremendous.”

“Our migraine therapy is demonstrating for the first time that relief can potentially be achieved within 10 minutes with sustained relief over a 24-hour period,” Nelson said. “The results of this Phase II study underscore our efforts to provide fast onset, long lasting, and convenient therapy to patients who are suffering from acute migraines.”

Furthermore, Tempo Migraine demonstrated total migraine relief (from a composite score of the four main symptoms of migraine) vs. placebo at 60 minutes and sustained relief at 24 hours for subjects receiving treatment, according to MAP. Tempo Migraine was also shown in the study to be well tolerated, with no serious adverse events reported, including cardiovascular or respiratory adverse events, the company said.

The second Phase II study evaluated pulmonary delivery of the drug in adults with compromised pulmonary function. The study was a randomized, double-blind, placebo-controlled, crossover study of Tempo Migraine in adult asthmatics. The trial demonstrated that the therapy was well tolerated by asthmatics with no serious adverse events reported, the company said. The pharmacokinetic profile in adult asthmatics was shown to be similar to non-asthmatic subjects receiving treatment in an earlier Phase I pharmacokinetic study.

Nelson said the company expects to start a Phase III study sometime in the second half of this year.

Sheffield Pharmaceutical developed the Tempo device, and when Sheffield went into bankruptcy in 2004 MAP bought some of those assets.

MAP estimates that about 32 million people in the U.S. and 33 million people in Western Europe suffer from migraine headaches. The company also noted that migraine treatment represents a $2 billion market in the U.S. and $3 billion market worldwide.

In January, MAP reported closing on a $25.25 million Series C preferred stock financing, with several biotech investors adding to the company’s seed round of $1.5 million and then a $30 million B round (Medical Device Daily, Jan. 26, 2006).