June 13th, 2007 4:43 pm By Ed Silverman - Thank you Pharmalot
The advisory committee unanimously voted against recommending the diet drug after hearing evidence that Acomplia increases the risk of suicidal behavior. Sanofi-Aventis didn’t help its cause by failing to convince the panel that the pill is safe. This is obviously a blow to the drugmaker, which already sells the diet pill in other countries, but was counting on the huge US market to make Acomplia a blockbuster.Source: Associated Press
“There is a reasonable suspicion we better learn some more and watch this affair more closely before we launch into massive use of this drug,” said panelist Dr. Jules Hirsch of Rockfeller University.
Given the microscope the FDA is under these days, it’s questionable whether the agency will approve Acomplia, especially since FDA officials usually follow the recommendations of its advisory panels. However, a final thumbs down may well create a black market for Acomplia, since many Americans are already reported to be crossing the border and buying the pill in Mexico.
Ironically, Sanofi-Aventis was going to call its pill Zimulti in the US, because the FDA thought Acomplia sounds too much like accomplished, which may be too suggestive for desperate dieters. So far, though, the drugmaker itself hasn’t accomplished anything. The FDA already declined to approve the pill to help smokers kick the habit.
In studies, patients given the once-daily tablet reported twice as many psychiatric side effects, including depression, anxiety and sleep problems, than those who received a placebo, Amy Egan, a FDA medical officer told the panel. “The numbers of events are small, but in aggregate they are worrisome,” she said.
Sanofi-Aventis execs suggested that patients be screened for depression before they are prescribed the drug, and also advised that patients visit their doctors five times during the first year of treatment to be reassessed to curtail any potential problems.
“Who is the right patient to receive rimonabant? Not everybody,” Richard Gural, the drugmaker’s vp of scientific affairs, told the panel The drug is not appropriate for anyone with a history of depression or suicidal thoughts, or who has been diagnosed with depression or is taking antidepressant medication, he conceded.
The FDA is to make a final decision on the drug by July 27.
The litany of mental problems associated with the drug clearly gave the panelists pause. “I think this is a drug that needs further understanding with respect to what it does to people’s psyche,” said panelist Sid Gilman, a University of Michigan neurologist.
Even if the FDA does approve the Acomplia the findings make it highly likely it would bear stern warnings. Company officials embraced the idea of such warnings, which could exclude FDA-approved use in some patients.
When used in conjunction with a modest-calorie diet and physical exercise, the drug significantly decreases body weight and waist circumference in overweight or obese patients, according to Sanofi-Aventis. In yearlong studies, patients on the drug lost roughly 14 pounds. Those given dummy pills lost only about 4 pounds. Patients regained weight when treatment was stopped after a year, the company said.
FDA reviewers didn’t question whether Zimulti works but remained worried the drug’s effect on the body could lead to an array of psychiatric symptoms, including anxiety, phobias, post-traumatic stress disorders and depression.
The company believes those increased cases were associated with depression or other disorders and weren’t directly caused by its drug. Egan, however, said they were. “We strongly believe that it is causal,” Egan said. She noted 88 percent of those reporting psychiatric problems while on the drug had no prior history of depression.
Furthermore, patients in the studies were carefully screened and monitored, suggesting the problems would be more common should the drug enter broad use, Egan added.
The screenings proposed by the company won’t keep the depressed and obese from Zimulti, warned Lynn McAfee, head of medical advocacy for the Council on Size & Weight Discrimination, a fat acceptance group. “If this gets out to be a real big deal in the public, you can figure out how to answer those questions to get the drug. It’s not going to stop anyone.”
The potential market for the drug is huge, as obesity rates have exploded in the past two decades. Today, nearly one in three American adults age 20 or older is obese, according to government data.
Sid Wolfe of Public Citizen said the obese are more likely to be depressed, and that many of them likely would take Zimulti along with the antidepressants they already use - with unknown consequences.
Rimonabant blocks the same pleasure centers in the body activated when pot smokers get the munchies. Blocking the receptors leads to patients eating less and losing weight. Sanofi-Aventis also believes the drug decreases fat storage.
The FDA previously told the French company it would not approve the drug to help smokers quit.
Sanofi-Aventis seeks to sell 20-milligram Zimulti tablets to the obese and to those who are overweight and have type 2 diabetes, high blood pressure or other conditions that put them at risk of cardiovascular disease.
There currently are two FDA-approved prescription drugs for the long-term treatment of obesity: Meridia, an appetite suppressant, and Xenical, which limits the amount of fat the body can absorb. Sales of Alli, a lower-dose version of Xenical that won’t require a prescription, start this week.