BioWorld International Correspondent

Paion AG got its stroke drug desmoteplase back on track by signing a new agreement with its existing partner H. Lundbeck A/S, under which the latter firm will take on future development and global commercialization responsibility for the compound.

Aachen, Germany-based Paion is receiving an up-front payment of €8 million (US$11.7 million) and could receive a total of €38 million and €25 million in development-based and sales-related royalties, respectively. It also would get double-digit royalties on product sales, although at a reduced rate compared to its earlier agreement with Copenhagen, Denmark-based Lundbeck. The latter company now has expanded its position to having worldwide rights. It previously held European rights only.

Desmoteplase, a genetically engineered version of a clot-busting protein isolated from the saliva of the vampire bat Desmodus rotundus, is being developed in order to extend the stroke treatment window from three hours to nine hours.

Its development was derailed during the summer, when data from a Phase III clinical trial indicated that desmoteplase performed no better than placebo, while it caused symptomatic intracranial bleeding in some patients.

Shortly afterward, its North American partner, New York-based Forest Laboratories Inc., terminated its interest in the program and returned its rights to Paion. (See BioWorld International, Sept. 5, 2007.)

However, a subsequent angiographic analysis of the data indicated that a high percentage of the patients in the trial did not have a blood clot in one of the main arteries of the brain, despite the presence of a penumbra of salvageable tissue that previously was considered to be a key indicator for the presence of visible clots in larger arteries and undetectable clots in smaller blood vessels.

A subgroup analysis indicated that the drug did demonstrate efficacy in patients with confirmed clots, in agreement with earlier studies, although the signal was not sufficient to be statistically significant, given the high placebo effect seen in the Phase III trial.

Paion and Lundbeck conducted the data analysis jointly, and they also consulted with stroke experts. "That has contributed to the comfort level we have reached with Lundbeck," Paion CEO Wolfgang Söhngen said on a conference call.

He was unable to set out a new development timeline for the product, but Lundbeck may commence a new Phase III clinical trial in the second half of 2008. "With the next study, the profile of the drug will become more clear," he said. "From our perspective, the market potential is difficult to assess at this moment."

For Paion, this is the second - and more serious - obstacle that desmoteplase has cleared. Last year, the steering committee on the Phase III trial put a temporary hold on recruitment, following an interim safety analysis. However, that was lifted very quickly, and the trial resumed without any protocol amendment.

"A vampire never really dies," joked Söhngen, in reference to the drug's origin. "Desmoteplase has always shown good potential for coming back when people think it's dead."