By Mary Welch

Recruitment for Phase III trials to test the systemic delivery of insulin through the lungs using a pulmonary delivery system developed by Inhale Therapeutic Systems Inc. has started. Enrollment and dosing will follow. The trials, which will include people with Type I and Type II diabetes, will take place at 117 sites throughout the U.S. and Canada. No timetable for filing a new drug application (NDA) has been set.

"Our partner, Pfizer, is really conducting the trials and will co-develop and co-promote the inhalable insulin product with Hoechst Marion Roussel," said Robert Chess, co-CEO of San Carlos, Calif.-based Inhale. "To have one of the top 10 pharmaceutical companies jointly co-developing and co-promoting your product is extremely beneficial for our company."

Earlier this month, Pfizer Inc., of New York, and Hoechst Marion Roussel, of Frankfurt, Germany, entered into worldwide agreements to manufacture insulin and co-develop and co-promote inhaled insulin based in Inhale's pulmonary delivery system. The two pharmaceutical giants will also construct and jointly own a manufacturing plant in Frankfurt to produce insulin.

Inhale's product, about the size of a flashlight, disperses a dose of dry-powder insulin into a small standing cloud within a clear chamber. It delivers the dose through the mouth and directly into the lungs, where it enters the blood system as rapid-acting insulin.

Pulmonary Delivery Aimed At Boosting Compliance

"Studies show that people don't take as much insulin as they should, because they don't like giving themselves shots," Chess told BioWorld Today in June. "By inhaling, it not only provides a more convenient way to take insulin, but we feel that more people will take all their prescribed insulin. And people who don't take any insulin, but should, would take it if they could inhale it, according to our research." (See BioWorld Today, June 18, 1998, p. 1.)

If more diabetics took insulin, complications from the disease — which include blindness, kidney failure, heart disease and stroke — likely would be reduced. The disease affects more than 142 million people worldwide, with the number of cases expected to double by 2025, according to the Geneva, Switzerland-based World Health Organization. The total cost of diabetes, including treatments and lost productivity, is $98 billion a year — five times the cost of HIV, AIDS and breast cancer combined, Chess said.

The Phase III trials will further evaluate clinical efficacy and safety within an expanded patient population. "Of course, the real endpoint is the control of glucose," Chess said.

Results of a three-month Phase IIb trial with 121 outpatients showed that inhaling insulin and taking it by injection resulted in similar blood glucose control and dose-to-dose reproducibility numbers. Patients, however, significantly preferred inhaling to injecting.

The collaboration between Inhale and Pfizer goes back to 1995, when Pfizer paid an undisclosed up-front fee and promised research. It also committed to research fees, milestone and royalty payments. Pfizer made equity investments of $5 million up front and $5 million after certain milestones were met. (See BioWorld Today, Jan. 20, 1995, p. 1.)

"We have received both payments. The second payment was made in 1997," Chess said. "We don't disclose the amount of the partnership, but we can say that it is several times the equity investment."

Inhale's stock (NASDAQ:INHL) closed Wednesday at $26.625, up $1. n