December 19, 2006
Ketek may lose two of three indications
An FDA advisory committee said Sanofi-Aventis’ Ketek should no longer be marketed for two of its three indications, bronchitis or sinusitis, saying the drug’s risks outweigh its benefits for these infections.
However, the committee voted 16 to 3 that the antibiotic should still be approved as a treatment for community-acquired pneumonia, just not as a first-line therapy. Members also said labeling should include a black-box warning to address risks associated with the drug.
The decision may cause other antibiotics approved for bronchitis and/or sinusitis to come under scrutiny, since the agency may have relied on data from the same type of non-inferiority trials for approval. While it doesn’t plan to reassess all of those prior approvals, “If we think there are others that warrant looking, we’ll take that into consideration,” said John Jenkins, MD, director, Office of New Drugs, CDER.
As to whether the FDA will rescind the two less serious indications, “I can’t announce today what our regulatory action will be, but we will certainly take the committee’s advice very seriously,” Jenkins said during a media briefing. The FDA typically follows the advice of its outside expert panels.
Doug Greene, Sanofi-Aventis chief US medical officer, said in a statement released after the meeting that the firm “will be in further discussion with the FDA regarding today’s recommendations.” During the meeting, the company had defended the drug, saying its benefits outweighed the risks.
Ketek, which has been the subject of congressional investigations due to concerns about liver toxicity and the controversy over a study used to establish the drug’s safety, was taken under advisement by two committees, the Anti-infective Drugs Advisory Committee and the Drug Safety Risk Management Advisory Committee.
Members voted 17 to 2 for removing the two indications, acute bacterial exacerbation of chronic bronchitis and acute bacterial sinusitis.
Areas of concern discussed during the meeting related to the use of non-inferiority trials, the standard when Ketek was approved in 2004. The two-day meeting also focused on four safety issues: liver toxicity, blurry vision, reports of loss of consciousness and exacerbation of myasthenia gravis, a neuromuscular disease.
Sanofi-Aventis revised Ketek’s label in June to include risk of liver damage and other issues.
The chair of the advisory committee said the votes could diminish interest in the development of anti-infective agents by the pharmaceutical industry.
Ketek had 2005 US sales of $193 million, according to IMS Health, The Wall Street Journal reported.