Biogen, Elan stand by MS drug after illnesses

The Associated Press
Published: August 1, 2008


NEW YORK: Biogen Idec Inc. and Elan Corp. defended their multiple sclerosis drug Tysabri on Friday after reporting two new cases of a potentially fatal side effect, saying the treatment is still worth the risk to patients.

There are no plans to pull the drug off the market, and the company said its current monitoring program for cases of a rare but sometimes fatal brain disorder is adequate.

The announcement of two new cases of the rare viral infection called progressive multifocal leukoencephalopathy, or PML, sent shares for both companies plummeting and reignited already simmering concerns about the drug's sales potential. It was pulled from the market in 2005 after being linked to the rare brain disease but was reintroduced under restricted sales conditions in mid-2006.

"These cases underscore the importance of continued clinical vigilance so PML can be discovered and managed appropriately," said Dr. Cecil B. Pickett, president of research and development at Biogen.

He and several other executives tried to allay concerns over additional cases during a conference call with financial investors and analysts Friday morning. The company said it would also hold calls with several physician and patient groups.

The risks associated with the drug are clearly labeled, the company said, and all patients are not only notified but have to sign a waiver acknowledging the risks. PML almost always occurs in people with a severe immune deficiency, as is the case with most patients taking Tysabri.

Multiple sclerosis is an autoimmune disorder that results in physical and neurological damage.

There are about 32,000 patients on Tysabri worldwide, with 17,800 in the U.S., the company said. It would not comment on its financial outlook, but did say future cases of Tysabri were anticipated and factored into the goal of eventually getting the drug to 100,000 patients worldwide.

The companies maintain the drug still has a favorable risk-reward profile, meaning it is more helpful than hurtful, and monitoring programs are set up in the U.S. and Europe to catch any potential cases of PML early. Those systems rely on physicians to test for the condition if they start to see symptoms. Biogen and Elan would not comment the number of suspected cases, only confirmed cases.

Both new cases came out of European, with the first patient having been on Tysabri for 17 months. Another, who is still hospitalized, had been on Tysabri for 14 months. Still, the company said it can count about 6,600 patients on the drug for about 18 months now, reinforcing its stance that the treatment is worth the risk.

Food and Drug Administration officials could not immediately be reached for comment as of Friday morning.

The broader market, meanwhile, remains concerned over the impact on sales, which nearly tripled to $200 million during the second-quarter. The treatments costs about $30,000 per year.

"We do not believe that Tysabri will be withdrawn, based on this data, but it is likely to spook investors as the true rate of PML in Tysabri monotherapy is unknown," Goldman Sachs analyst Stephen McGarry said in a note to Elan investors.

Shares of Cambridge, Massachusetts-based Biogen fell to $50.28, their lowest point in more than a year, while shares of Ireland-based Elan fell to $10.67, their lowest point in nearly three years.

Obesity Pill From Sanofi Gets Review

By JENNIFER CORBETT DOOREN

WASHINGTON -- The Food and Drug Administration Monday said Acomplia, a proposed weight-loss drug by Sanofi-Aventis SA, was effective at promoting weight loss but appeared to double the rate of suicidal thoughts and behavior.

Acomplia is sold in several European countries and the Paris company is seeking approval to sell the drug in the U.S., a key market that would likely propel it to blockbuster status of $1 billion or more in annual sales. Acomplia, which would be sold under the brand name Zimulti in the U.S., faces a review Wednesday by an FDA panel of outside medical experts. Acomplia is also known by its generic name, rimonabant.


WSJ's health blogger Jacob Goldstein discusses new FDA documents that state Acomplia from Sanofi-Aventis was effective at promoting weight loss but appeared to double the rate of suicidal thoughts and behavior.

The FDA typically follows its panels' advice but isn't required to do so. The FDA is set to make a final decision on whether to approve the drug by the end of July. The panel will be asked to decide several questions, including whether rimonabant should be approved or if additional studies are needed. The panel will also have to decide if it believes rimonabant increases the incidence of "suicidality," psychiatric and neurological adverse events, or side effects and seizures.

Suicidality is a term used to describe an increase in suicidal thoughts and behaviors and doesn't refer to completed suicides.

In briefing documents posted to its Web site Monday, the FDA said the 20-milligram dose of rimonabant was "associated with statistically and clinically significant weight loss." However, the FDA said it was concerned about an increase in psychiatric side effects as well as seizures. Sanofi had studied a 5- and a 20-milligram dose. The FDA said the 5-milligram dose wasn't effective at helping people lose weight.

Sanofi is seeking FDA approval to sell a 20-milligram dose to people considered obese and to people who are overweight who have at least one cardiovascular disease risk factor such as high blood pressure. Studies of the drug typically showed patients on the drug lost about 15 pounds over the course of a year while those in the placebo group lost about three pounds. They also had gains in HDL, or "good," cholesterol and declines in decline in triglyceride levels, or a type of fat found in the blood.

Rimonabant is designed to help block a chemical in the endocannabinoid system, a physiological system in the body that is believed to play a role in how the body regulates food intake. The FDA is concerned, however, that blocking the same chemical could increase the risk for other problems including mood disorders and neurodegenerative disorders like multiple sclerosis.

The FDA reviewed clinical studies of the drug as well as post-marketing reports of the drug from Europe. The agency said the 20-milligram dose of rimonabant is "statistically, significantly increased suicidality" compared to placebo or a fake drug.

The agency said a detailed meta-analysis of the suicidality data will be presented to the advisory panel Wednesday, but noted that patients on rimonabant were twice as likely to report an increase in "suicidality."

The FDA also said there was a higher rate of other psychiatric side effects among rimonabant users and the drug increased the risk of seizures. The agency said one set of studies showed 26% of patients on the 20-milligram dose of rimonabant reported a psychiatric side effect -- ranging from depression to insomnia -- compared to 14% of patients in the placebo group.

"We anticipate that much of the discussion at the advisory committee meeting will center on the relationship between rimonabant and depression, and on the methodology, results and interpretation of FDA's meta-analytic assessment of suicidality from completed rimonabant studies," the FDA said in a letter to panel members.

In its briefing document, Sanofi said that the "overall benefits in body weight, waist circumference and metabolic parameters...outweigh the risks that are manageable in clinical practice." The company said it would recommend that rimonabant not be used in patients with an existing psychiatric disorder like major depression and that the drug be used "cautiously" in patients with epilepsy, which causes seizures.

Last February, the FDA rejected Acomplia as a smoking-cessation product and said it needed more information on psychiatric side effects before it would consider approving the drug as a weight-loss treatment.

Sanofi shares edged lower on the New York Stock Exchange, falling 36 cents, or 0.8%, to $45.14.

Write to Jennifer Corbett Dooren at jennifer.corbett-dooren@dowjones.com