BioWorld International Correspondent

Paion AG is accelerating the Phase III development program for its lead compound, the recombinant plasminogen activator Desmoteplase, which is in development for treating acute ischemic stroke.

The clot-busting compound, a genetically engineered version of a protein derived from the saliva of the vampire bat, Desmodus rotundus, already is undergoing a Phase III clinical trial, DIAS-2, which Aachen, Germany-based Paion is conducting with its North American partner Forest Laboratories Inc., of New York. The compound, which has fast-track status from the FDA, is being developed to widen the treatment window for stroke patients to three to nine hours, well beyond the current three-hour limit associated with tissue plasminogen activator, marketed by Genentech Inc., of South San Francisco.

Late last month, Paion said that the study was on target to complete enrollment by the end of 2006 and that the second of three planned interim safety analyses indicated that the rate of symptomatic bleedings, a major concern for treating physicians, had been below pre-defined levels.

DIAS-2, which is slated to recruit 186 patients in total, will be completed by the middle of 2007. Rather than wait for the conclusion of that study, Paion opted to bring forward the start of a second Phase III study, which will be conducted initially in Europe and other territories outside the U.S., to the fourth quarter, assuming it receives permission from regulatory authorities.

That will give it additional safety data that could help it decide on how to proceed with a possible regulatory filing for the compound, Peer Nils Schroder, head of public relations at Paion, told BioWorld International. "We want to have the maximum number of patients being treated with Desmoteplase to strengthen that safety database," he said.

Obtaining early conditional approval on the basis of interim data from DIAS-2 would be the "optimum" outcome, Schroder said, and the second study providing additional supporting safety data already would be under way.

The second study will be of a similar scale to DIAS-2, which has recruited around two-thirds of the 186 patients set out in the study design. The FDA has required Paion and Forest to investigate the efficacy of two different doses of Desmoteplase - 125 mcg and 90 mcg. The second study will be limited to a single dose, Schroder said.

"We expect only a 125-mcg dose," he said. That exhibited best clinical outcome in a previous Phase II trial. Paion is embarking on the second Phase III trial with the agreement of its partner, H. Lundbeck A/S, of Copenhagen, Denmark, which signed a commercialization agreement covering Europe and Asia last year. (See BioWorld International, July 13, 2005.)

Paion also said it would book revenues of €3 million (US$3.9 million) in the third quarter, arising out of its agreement with Lundbeck.