CD&D

SAN DIEGO — Stroke meets many of biotech and pharma's requirements for an attractive development opportunity, Warren Wasiewski, vice president and chief medical officer of Neurobiological Technologies (Emeryville, California), said during the International Stroke Conference here. It's a large global market, but it can be penetrated by a niche sales force targeting stroke centers. Additionally, with tPA only being used in about 2% of stroke patients, there is a large unmet need and almost no competition.

But despite all this, Big Pharma has very little appetite for developing new stroke drugs, Wasiewski said during a panel. "There have been too many failures," he lamented.

Among the casualties are Neurobiological Technologies' own Viprinex (ancrod), which was the subject of two Phase III stroke trials that were halted in December after a futility analysis indicated they were unlikely to show benefit.

Other failures include Renovis (Emeryville, California) and AstraZeneca's (London) NXY-059, which was discontinued after failing a Phase III study, and Nuvelo's (San Carlos, California) alfimeprase, which had failed two Phase III studies in peripheral occlusion and catheter occlusion before being tried in stroke and eventually discontinued as Nuvelo did a reverse merger with ARCA Biopharma (Broomfield, Colorado).

There also have been plenty of smaller setbacks. Wyeth Pharmaceuticals (Collegeville, Pennsylvania) ended a Hedgehog agonist partnership with Curis (Cambridge, Massachusetts) in stroke and other indications, and Ambit Biosciences (San Diego) discontinued a pre-clinical stroke program.

Meanwhile, a German study of anemia drug Eprex (epoetin alfa) from Johnson & Johnson (New Brunswick, New Jersey) in stroke caused an imbalance of deaths, and Stem Cell Therapeutics' (Calgary, Alberta) Phase IIb stroke trial, which also involves EPO, remains on hold.

Some failed candidates continue to move forward. Paion AG's (Aachen, Germany) clot-buster desmoteplase failed a Phase III stroke trial and got dumped by partner Forest Laboratories (New York) only to be picked up by H. Lundbeck A/S (Copenhagen, Denmark), which started two new Phase III trials in December.

And sometimes moving forward in the face of a setback can pay off. ImaRx Therapeutics (Redmond, Washington) ran into trouble with intracranial hemorrhage associated with high doses of stroke drug MRX-801, but Phase I/II data presented at the conference showed that lower doses improved recanalization and clinical outcomes without bleeding problems.

Other acute stroke programs in development include ThromboGenics NV's (Heverlee, Belgium) Phase II microplasmin, Athersys' (Cleveland) Phase I adult stem cell product MultiStem, Remedy Pharmaceuticals' (New York) pre-clinical ATP gated channel program, and Aldagen's (Durham, North Carolina) pre-clinical adult stem cell program, while other companies are trying a preventative approach.

Why have there been so many failures? Aside from the fact that nine out of 10 biotech products fail, and the brain is a particularly tricky organ that lowers those odds, Claiborne Johnston of the University of California, San Francisco said a review of more than 1,000 pre-clinical stroke drugs showed no difference in data indicating a likelihood of success for those that were advanced compared to those that were shelved.