December 7th, 2004

"Accutane becomes more controversial"

Ever since Accutane made its 1982 U.S. debut, intended to treat severe forms of acne that failed to respond to other treatments, it has been the source of medical and regulatory controversy. Now, a Florida lawsuit against Accutane drugmaker Hoffmann-La Roche is charging the company disregarded its internal doctor''s recommendation that users of the drug are monitored for signs of depression and that a warning indicating this is added to the label.

According to evidence, Hoffmann-La Roche marketing officials argued such Accutane warnings could cost the firm sales or prompt lawsuits. Both the doctor''s recommendation and the marketing debate have so far not been publicized in Accutane''s over 20-year controversy.

No official findings link Accutane to depression or any other psychiatric illnesses, but Roche''s global head of drug safety, Martin Huber, testified in a pretrial deposition for the Florida case that the firm''s internal analysis showed Accutane “probably caused” depression and other psychiatric illnesses in some patients, according to the court file summary of his deposition.

Huber also testified that the FDA and Roche consultants had told company officials the rate of depression among Accutane users was 1.5 times higher than among non-users, according to the summary. Roche''s global head of drug regulatory affairs, Daniel Zabrowski, testified separately that a company doctor, Peter Schifferdecker, based at the Basel, Switzerland headquarters, studied data on depression and other adverse psychiatric events reported by Accutane patients in 1997.

According to the summary of Zabrowski''s deposition testimony, Schifferdecker wrote a report recommending changes in Accutane''s U.S. label and core data sheet, the internal company document used by Roche to ensure consistency of the firm''s products worldwide. Legal summaries of depositions by Zabrowski, as well as other Roche officials, show Schifferdecker recommended Accutane''s U.S. label warn users “should be supervised for signs of depression during therapy and, if necessary, referred for appropriate treatment.”

Records in the Florida case show that Roche modified the core data sheet to reflect Schifferdecker''s recommendation, but Zabrowski testified Roche''s marketing division was worried the monitoring warning on Accutane''s U.S. label could hurt sales. Medical consultants in the marketing department revised Schifferdecker''s report to remove the reference to monitoring, which was then sent to the FDA, according to the summary of Zabrowski''s deposition.

There are also internal records of another marketing staffer who wrote an email stating any decision that would “add the proposed label change” should not be finalized “without full consideration of the enhancements to Dr. Schifferdecker''s report.” Currently, Roche is the target of about 70 lawsuits for allegations of adverse reactions because of Accutane. Plaintiffs claim Accutane adverse effects include suicides, depression, birth defects and gastrointestinal injuries.

The internal Roche documents and employee testimony comes at an especially bad time. At the end of September, Merck''s arthritis pain reliever Vioxx was recalled. IN an already heightened scrutiny of drug companies and of the FDA''s oversight of the industry, an FDA whistleblower testifying in front of a Senate panel last month regarding the Vioxx recall named Accutane as one of the five drugs currently on the market that should be studied for a possible withdrawal due to safety concerns.