FDA Center for Drug Evaluation & Research Director Janet Woodcock, MD, is scheduled to testify on patient safety issues related to Roche's acne drug Accutane during a Dec. 5 hearing convened by the House Government Reform Committee.

The hearing will focus on reports of psychiatric adverse events associated with isotretinoin.

FDA's Dermatologic & Ophthalmic Drugs Advisory Committee met in September to review the reports, and the committee unanimously agreed that more risk management for Accutane-associated psychiatric adverse events is necessary (¹ Also see "FDA To Study "Labeling Fatigue": Do Serial Changes Influence Prescribing?" - Pink Sheet, 25 September, 2000.).

Woodcock is scheduled to be accompanied by Office of Drug Evaluation V Deputy Director Jonca Bull, MD, Medical Review Officer and Phyllis Huene, MD, and Clinical Reviewer David Bostwick, MD. The Accutane NDA is handled by the Dermatologic and Dental Drug Products Division within ODE V.

Committee members such as Ranking Democrat Waxman (D-Calif.) could use the hearing as a forum to air more general concerns about drug safety.

The hearing will take place one week after Glaxo Wellcome withdrew the irritable bowel syndrome therapy Lotronex - the eighth product approved under the user fee program to be withdrawn or sharply restricted due to side effects (² Also see "Glaxo Lotronex Withdrawal Follows Failed Risk Management Negotiations" - Pink Sheet, 4 December, 2000.).

Roche Consultant Douglas Jacobs, MD, Harvard Medical School, will also testify at the hearing.

Jacobs spoke during the September advisory committee on behalf of Roche, noting "no significant relationship" between Accutane use and concurrent depression. "There's no exacerbation of underlying psychiatric disorders," he said.

Roche also plans to submit a written statement to the committee, the company said.

The American Academy of Dermatology will be represented at the hearing by David Pariser, MD, Pariser Dermatology Specialists. He has been asked to educate the committee on acne, the committee said.

AAD released a policy statement on isotretinoin Nov. 30 calling for "a study designed to determine if there is a direct causative link between isotretinoin and psychiatric events."

Other witnesses at the hearing will include Rush Medical School Assistant Professor of Pharmacology James O'Donnel, who will present the position that a link between Accutane use and depression has been demonstrated, the committee said.

A panel of consumers representing the "family perspective" will also testify. The panel includes two sets of parents of children who committed suicide while on Accutane, as well as a patient who attempted suicide while taking the drug.

Following the suicide attempt, the patient was continued on the drug until February 1998, when Roche issued a "Dear Doctor" letter notifying healthcare professionals of Accutane's link to depression. The warning section of labeling was revised to add a boldface notice that "Accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts and suicide."

The acne drug's link to psychiatric adverse events has been the subject of recent congressional inquiry. Rep. Stupak (D-Mich.), whose son committed suicide in May while on Accutane, voiced a need for independent controlled studies on Accutane's link to psychiatric adverse events in October letters to Roche and FDA.

The letters outline recommendations to improve Accutane patient safety while additional research is conducted.

The recommendations include a moratorium on direct-to-consumer advertising aimed at teenagers. Reps. Waxman (D-Calif.), Brown (D-Ohio), Barrett (D-Wisc.), Roukema (R-N.J.), Coburn (R-Okla.), Wamp (R-Tenn.) and Bryant (R-Tenn.) also signed the request.

In an Oct. 17 response, Roche CEO Patrick Zenner agreed to cease educational television ads targeted at teenagers until the link between Accutane and suicide, suicide attempts, suicidal ideation and depression has been studied. The company will continue to publish print educational ads, Roche said.

"We are discontinuing televised non-branded acne education messages directed to young people until further risk management steps...have been addressed," the letter says. Roche does not disseminate any branded DTC advertising for Accutane.

During the September advisory committee review, several committee members objected to a Roche non-branded education print advertisement, which depicted a teenager with acne, because it might attract patients whose acne was not severe enough to require Accutane treatment. The drug is indicated for treatment of severe recalcitrant nodular acne.

Through May, FDA had received 147 case reports of suicide and hospitalized depression associated with the drug since its launch in 1982.

The Stupak letters to FDA and Roche recommend that Accutane patients receive and sign an informed consent form clearly warning of Accutane's risk of depression, suicide and other psychiatric disorders when the drug is prescribed. Roche is in the process of updating its consent form to incorporate the psychiatric information included in labeling, the company said.

Roche said it is also exchanging Accutane packages in the market to assure that all drug packaging is consistent with the 1998 updates to labeling.

Roche is also working with FDA on an Accutane Medication Guide, which will include a discussion of psychiatric adverse events, the company said.

The hearing on Accutane's association with psychiatric disorders is taking place while Roche is awaiting approval for an Accutane line extension. A once-daily formulation of isotretinoin has been "approvable" at FDA since Oct. 27.

Roche may consider phasing out the twice-daily Accutane formulation three years after launching the once-daily version (³ Also see "Accutane Once-Daily Version Should Have Three-Year Phase-In - FDA Cmte." - Pink Sheet, 25 September, 2000.).

The decision to bring Accutane before the Government Reform Committee is likely related to the interest of Chairman Burton (R-Ind.) in patient safety issues. Burton has been investigating vaccine safety in part due to the occurrence of potential vaccine-associated adverse events in his family.

House Accutane Safety Hearing Will Include Testimony From FDA's Woodcock

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