By Charles Craig
Alkermes Inc. shares fell 31 percent Monday after the Cambridge, Mass., company reported disappointing results from a Phase II trial of its drug delivery agent, which is designed to ferry therapeutic compounds through the hard-to-cross blood-brain barrier.
The U.S. study was the third Phase II trial, but the only one designed with a placebo-controlled group to yield statistically significant findings on the delivery system's efficacy. Two previous European studies, which produced positive findings on effectiveness of the drug delivery agent, were open-label evaluations. (See BioWorld Today, Dec. 19, 1996, p. 1.)
Richard Pops, Alkermes CEO, said the U.S. trial did not meet its primary endpoint, but data from the three Phase II studies support proceeding to Phase III trials.
Alkermes' product, receptor-mediate permeabilizer 7 (RMP-7), is a synthetic analogue of bradykinin, which is a naturally occurring molecule with vascular permeability properties. Use of RMP-7 is aimed at getting more drug into a patient's brain than is possible when the compound alone is administered.
By relaxing the tight cellular configuration of the blood-brain barrier, RMP-7 also is viewed as a method for delivering drugs that have not been prescribed because they could not penetrate into the brain.
In Alkermes' three Phase II trials, RMP-7 was used with the chemotherapeutic drug carboplatin for treatment of recurrent malignant brain tumors.
The primary endpoint for the U.S. study was evaluation of time to tumor progression in patients treated with RMP-7 and carboplatin compared with progression in patients receiving carboplatin and a placebo. Time to progression was defined as how fast the tumor increased in volume by 50 percent.
The data revealed intravenous treatments of RMP-7 and carboplatin did not result in significantly slower progression than intravenous administrations of carboplatin alone.
Pops said the progression times for all patients were "brief." He added early analysis of other endpoints, such as survival and progression of functional impairment, indicate patients benefited from the RMP-7-delivered carboplatin compared with the drug itself.
Pops said Alkermes intends to proceed with Phase III studies of RMP-7 and carboplatin following further review of the Phase II trial data and discussions with the clinical investigators and FDA officials.
He added the U.S. study was designed as a controlled trial to support submission of a new drug application with the FDA based on Phase II results. New treatments for brain cancer are given accelerated reviews because of the life-threatening severity of the disease.
If the primary endpoint on the U.S. Phase II trial were achieved, Alkermes could have filed for market clearance of the treatment without conducting the Phase III studies normally required for FDA approval.
"We're optimistic," Pops said. "We've completed a Phase II series with a wealth of data to move into Phase III."
However, investors punished Alkermes for missing the U.S. Phase II study's primary endpoint. Shares dropped $6.25 to $14.
Pops blamed the general slump in biotechnology stocks for exacerbating the market's reaction to the negative clinical trial news.
"Overall the market is awful," he said. "There are sellers, but no buyers."
The RMP-7 program is supported by a limited partnership, called Alkermes Clinical Partners, set up in April 1992 to develop the drug delivery agent.
RMP-7 is one of several Alkermes drug delivery systems. Another is ProLease, which uses polymeric microspheres similar to dissolving sutures to achieve sustained release and biological activity of large, unstable molecules such as proteins and peptides. And a third technology, Medisorb, is similar to ProLease but designed for sustained release of traditional small molecule drugs.
Both ProLease and Medisorb are the focus of partnerships with pharmaceutical and biotechnology companies.
In February, Alza Corp., of Palo Alto, Calif., bought a 9.7 percent stake in Alkermes, buying 2 million shares, at $25 per share, for $50 million. Alza also is a drug delivery company specializing in sustained-release forms of traditional pharmaceuticals.
Pops said Alkermes has $90 million in cash. The company's fiscal year ended Monday. For the last three quarters of 1996, Alkermes reported a net loss of $13.9 million. *