By Lisa Seachrist

Washington Editor

Just one week after announcing excellent financial results for the third quarter, Biogen Inc. stopped six Phase II clinical trials of Antova, a humanized anti-CD40 ligand antibody, as a result of thrombo-embolic events.

The company's stock slipped 11 percent in trading of 18 million shares on the news as several analysts downgraded the stock. The Cambridge, Mass.-based company's stock (NASDAQ:BGEN) closed at $64.375, down $8.187. It lost $19.94, or nearly 24 percent, for the week.

"We have seen several of these clotting events over time," said Kathryn Bloom, Biogen's director of communications. "We do not know if it is the drug. A lot of the patients in these studies were a risk for blood clots as a result of their underlying medical conditions. The company was very proactive in deciding to halt the studies and the FDA concurred with us."

Biogen began Phase II clinical trials of Antova as a possible therapy for Factor VIII inhibitor syndrome, islet cell transplantation, multiple sclerosis, immune thrombocytopenic purpura (ITP), kidney transplantation and systemic lupus erythematosus. The company isn't releasing the number of patients who have been dosed with Antova nor the number of patients who suffered from the blood clots, but the events occurred in more than one indication.

Bloom said at this time the studies in Factor VIII inhibitor syndrome, islet cell transplantation and multiple sclerosis have been placed on hold. Patients already receiving the drug in the renal transplantation program will continue on therapy and those patients who've benefited from therapy in the ITP indication will continue on the drug. Biogen and the FDA are still negotiating the continuation of the lupus trial.

"We are being tight-lipped about the specifics because we have to evaluate the data and determine what is happening here," Bloom said. "We're not going to start speculating until we have some solid information."

Albert Rauch, senior vice president and biotech analyst with First Union Securities Inc. in Chicago, said the fact that the adverse events happened in several indications doesn't bode well for Antova.

"My feeling is this news is the end of Antova," Rauch said. "When you have clots forming in patients, they are now at risk for strokes and heart attacks. They are seeing this in more than one indication and that is what concerns me."

Rauch said it was likely the antibody interacting with platelets or some other clotting factor - and not the CD40-ligand as a drug target - was the root of the problem. He noted it is possible to retool the antibody to make clotting less likely, but such an effort would take a significant amount of time.

"I believe Antova is dead in its present form," Rauch said.

Lesley Marino, an analyst at BancBoston Robertson Stephens Inc. in New York, agreed with Rauch that the news was a major setback, but she still sees life for the drug.

"I think this news is a big deal," Marino said. "But it's still a little premature to say Antova is dead. We are really just going to have to wait and see."

Marino noted if it turns out the clotting events are rare or only certain patients are susceptible, the drug could move forward. Both analysts agree the bigger problem for Biogen is a gap in its product pipeline. In addition to Avonex - its blockbuster multiple sclerosis drug - and Antova, Biogen is developing Andentri (adenosine A1 antagonist) in Phase II as a therapy for edema associated with congestive heart failure and Amevive, a human fusion protein in Phase III studies for the treatment of moderate-to-severe psoriasis.

"There has always been a gap between Avonex and what product comes next," Marino said. "With Antova, at least temporarily, out of the picture, that only leaves them with two products. So the Street's reaction was a reasonable one, considering."

Rauch agreed, noting Amevive is the most developed product that could become a billion dollar drug, but it is unlikely to make it to market before 2003.

"I think it would be a pretty good strategic move for them to make an acquisition to enhance their pipeline," Marino said. "If you look at their history, though, they've not had a lot of activity like that in the past. But, it would be a reasonable move."