New hope for Alzheimer's treatment tempered by earlier failures

The latest promising Alzheimer's disease drug trial is causing a burst of excitement for Biogen Idec Inc. investors. It may be too early to celebrate.

Other Alzheimer's drugs that later failed in larger, more comprehensive effectiveness tests showed the same sort of initial promise as Biogen's, say neurologists. The biotechnology company said yesterday that it would move the drug, BIIB037, into a final-stage trial based on positive Phase 1 data, sending its shares up as much as 9.1 percent when the market opened.

The trial of fewer than 200 patients showed the drug removed a protein fragment that causes plaques in the brain that are a hallmark of Alzheimer's. Patients also did better on cognitive tests, Doug Williams, Biogen's head of research and development, said at a Deutsche Bank conference this week.

That's "good news, but not necessarily good enough news," said Samuel Gandy, director of New York's Mount Sinai Center for Cognitive Health. What counts as statistical success in a trial doesn't always mean a meaningful clinical difference for doctors and patients, he said.

The investor excitement over Biogen's data reflects the desperate need for a successful drug. There have been more than 100 failed attempts to develop a treatment for the neurodegenerative disease since 1998, according to a 2012 report by the trade group Pharmaceutical Research and Manufacturers of America. Only a handful of drugs have been approved to manage symptoms, and none to treat the cause.

Meanwhile, the Alzheimer's population is growing. An estimated 5.2 million Americans have the disease, according to the Alzheimer's Association. By 2025, that number is expected to grow 40 percent as the U.S. population ages. Alzheimer's causes memory loss, dementia, and is the sixth-leading cause of death in the U.S., according to the Alzheimer's Association.

Biogen said it will present full data from the trial early next year, which may clear up questions on how much the drug helped.

Biogen hasn't said how many patients were used in the analysis or given details on how long they took the drug. While Schmidt said he thinks about 200 patients were included, Mark Schoenebaum, an analyst at Evercore ISI, estimates closer to 150 patients, since the trial was still bringing in new participants.

Biogen spokeswoman Kate Niazi-Sai declined to say exactly how many patients were counted in the analysis, saying only that "the majority" of about 200 patients were included.

Other drugs that have showed early promise haven't cleared later hurdles. Eli Lilly & Co.'s experimental drug "solanezumab showed a statistically significant benefit on cognitive testing but that was not reflected in any meaningful benefit," Gandy said by e-mail. The drug failed in a final-stage trial of patients with mild to moderate patients. Lilly is now examining it for earlier-stage disease.

The market for Alzheimer's drugs may reach $30 billion worldwide at its peak, according to Schoenebaum. Biogen's BIIB037 could reach $10 billion worldwide, according to Ian Somaiya, an analyst at Nomura Securities International Inc.

Biogen is following Lilly and Roche Holding AG in targeting beta amyloid, the protein fragment that causes the brain plaques. Pfizer Inc., Johnson & Johnson and Elan Corp. also codeveloped a drug, which failed, with the same target.

Roche's drug, called gantenerumab, is in a final-stage trial. Merck & Co. has a drug, MK-8931, that works by blocking amyloid production rather than removing it from the brain and belongs to a class called BACE inhibitors. It's also in late- stage tests.

One of the drugs will eventually show that it works, said Schoenebaum. "It's becoming harder and harder to argue that this approach will not hit in Phase 3 trials," he said.

Another lingering question is on safety. Biogen said its drug caused some mild to moderate cases of brain swelling, or ARIA, which stands for amyloid-related imaging abnormality. The side was self-resolving, and "we believe that we have a safety window to work with," Williams said.

The next step for Biogen is to design and conduct a large trial enrolling thousands of patients. Along with cognition, the next trial may include "functional" endpoints, said Michael Yee, an analyst at RBC Capital Markets, by telephone. "Memory is one thing — can you remember words and numbers — functional includes being able to feed yourself, go to the bathroom."

It may take until 2017 or 2018 before Biogen's final results read out, said Schoenebaum.