Safety review boosts hopes for return of MS drug
No more cases of brain disease
Biogen Idec Inc. said yesterday it screened patients who took the multiple sclerosis drug Tysabri and didn't find any new cases of the rare brain disease that led the company to pull it off the market.
The report, part of an ongoing safety evaluation of Tysabri, renewed hopes for multiple sclerosis patients who have clamored for the drug since it was voluntarily suspended by Biogen Idec and its partner, Elan Corp., Feb. 28 after a patient in a clinical trial of the drug died of the brain disease. The review looked at patients who were treated with Tysabri in long-term clinical trials and those who took it during the three months it was on the market.
If it is determined that Tysabri is safe, ''there's going to be a lot of happy people, and I'm not talking about shareholders," said Art Mellor, president and chief executive of the Accelerated Cure Project, a group that funds MS research.
Shareholders, of course, did find reason to celebrate. Yesterday's news sent both companies' stock prices climbing. Shares of Biogen Idec, which is based in Cambridge, gained 7 percent to close at $41.24. Elan -- whose future hinges largely on Tysabri -- rose $1.09, or nearly 14 percent, to close at $9.09.
Biogen Idec executives, who have been guarded in their comments about Tysabri's possible return, made their most optimistic comments to date on the drug's prospects.
''We're encouraged that we now have a better understanding of what the risk is, and we're encouraged that it'll be coming back onto the market," James C. Mullen, Biogen Idec's chief executive, said in a conference call. ''Until the regulators have time to look through this information, it's going to be hard to predict what the timeline is going to be."
One key question is whether the Food and Drug Administration might require additional clinical trial data before allowing Tysabri to be prescribed. Such studies could take several years, giving an advantage to other experimental MS treatments that might receive approval during that time.
Dr. Dennis Bourdette, chairman of the neurology department at Oregon Health & Science University, said in a recent interview that he would prefer a trial in which patients would be treated with Tysabri while being monitored for the appearance of the virus that causes the disease, called progressive multifocal leukoencephalopathy. ''I'd think two years would be a good study period," he said. If the results were positive, Bourdette said, he could envision Tysabri being allowed back on the market.
Multiple sclerosis is a disease in which the body's immune system attacks the protective outer sheath of neurons in the central nervous system. It typically progresses over many years, causing steadily worsening symptoms including paralysis, loss of vision, and numbness.
The FDA approved the drug in November after accelerated review of one year's data from an ongoing two-year trial. Tysabri showed a remarkable ability to prevent debilitating relapses in the type of MS characterized by flare-ups and periods of remission. The data indicated Tysabri would be far more effective than current treatments on the market, including Biogen Idec's Avonex and Rebif, a similar treatment sold by Serono SA.
But the companies stopped sales and trials Feb. 28 after one patient died of PML after receiving 37 doses of Tysabri, along with Avonex, in a company trial. A second patient in the combination trial, a 46-year-old man, also developed PML, but he survived and continues to recover from the devastating disease.
In March, the companies said a third patient had contracted PML in a trial using Tysabri to treat Crohn's disease, an inflammatory ailment of the large intestine. The patient, who died in 2003, was re-diagnosed based on preserved tissue samples.
The first two cases indicated a possible connection between using Tysabri and Avonex in combination and the risk of developing PML. That has bolstered the belief among some doctors that Tysabri by itself would prove safe to treat MS.
In June, the Globe and other newspapers reported two possible additional PML cases, based on FDA records. But results of the review released yesterday said those cases were not PML, and show that no other MS patients who participated in the trials developed signs of the disease. Nor did the review find any PML cases among the 5,000 patients who took Tysabri during the three months it was on the market.
''We feel confident that if you haven't had signs or symptoms of PML yet, that eliminates the possibility of you developing PML," said Amy Brockelman, a Biogen Idec spokeswoman.
Patients who took Tysabri in trials for Crohn's disease or rheumatoid arthritis are still being evaluated. That part of the safety review is expected to be completed by late September.
Biogen Idec said it would soon submit paperwork to the FDA to restart the clinical trials halted in February. The company said it would try to recruit patients who previously participated. Such testing will provide long-term data on the safety and effectiveness of Tysabri.
A key question is whether the FDA or European regulators will require results from new trials before allowing Tysabri back on the market. That could delay reintroduction by several years.
''We do not believe we would need additional clinical trials to return to the market," Brockelman said.
Some doctors agreed.
''I personally think it may very well be reasonable to allow the drug back on the market to be used in patients who are seriously ill and are not responding to other therapies," said Dr. Aaron Miller, chief medical officer of the National Multiple Sclerosis Society and medical director at Corinne Goldsmith Dickinson Center for Multiple Sclerosis in New York.
Still, it seems unlikely that Tysabri will be able develop into the blockbuster drug it once seemed destined to become. When it was introduced, Tysabri was a front-line therapy with distinct benefits, compared to its competitors. Now, because of the higher risks associated with the drug, Tysabri may be reserved for much smaller subsets of MS patients.
The drug would most likely be used for patients who haven't responded to existing treatments and those for whom the treatments no longer provide significant benefits, said Jennifer M. Chao, senior analyst at Deutsche Bank. ''It's fair to say that a Tysabri commercial re-launch will face significant inertia, in any regard."
Jeffrey Krasner can be reached at krasner@globe.com.