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Sanofi-Aventis could be in for rough ride on Wednesday when advisers for the US regulators review the Franco-German drugmaker’s obesity pill Acomplia® (rimonabant).
In briefing documents released ahead of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee review panel meeting, agency staff expressed concern over “increased frequencies of psychiatric adverse effects” including suicide and seizures linked to Acomplia which, if approved, will be sold as Zimulti®.
The drug has been available in Europe since June 2006 but the FDA has not looked too kindly on Acomplia in the past, despite its first application for US approval being submitted in April 2005. In February this year the FDA said the review period for rimonabant had been extended for another three months, until 27 July, representing another postponement by the agency.
The agency had asked for extra data and the FDA staff stated that “among the most significant adverse events throughout the phase III programme were those in the primary system organ class psychiatric disorders, specifically depressive events, anxiety, psychomotor agitation, and sleep disorders”. Sanofi noted in its briefing document for the advisory committee that “a greater incidence of dizziness, anxiety, depressed mood and depressive disorders was observed in the 20mg rimonabant group” for obese patients, compared to placebo.
As a result, Sanofi is proposing that rimonabant “should not be initiated in patients with uncontrolled psychiatric illness such as a major depression” and notes that “there is limited data” in patients taking antidepressants in combination with its drug, “therefore the use of rimonabant is not recommended in these patients”.
The study also found that depressive disorders, including suicidality-related reactions, were reported in 133 medically confirmed cases, a ratio of 12.2 per 10,000 treated patients. Of these, 26% were considered serious and it was found that adverse reactions started during the first month in 99 cases. Fifty-four patients had a prior psychiatric history and/or suffered from psychiatric diseases.
Nevertheless, over a 12-month period, patients on Acomplia lost an average of 5.3kg compared to 1.4kg for those who received placebo and the treatment also improved measures of patients’ blood sugar and high-density lipoprotein or ‘good’ cholesterol levels. Sanofi added that the drug’s “overall benefits in body weight, waist circumference and metabolic parameters outweigh the risks that are manageable in clinical practice”. Whether the FDA agrees will become clearer on Wednesday.