FDA has asked GSK and Takeda to place boxed warnings of congestive heart failure risks on the labeling for their type 2 diabetes drugs, Avandia and Actos.
That revelation came in FDA commissioner Andrew von Eschenbach’s testimony today before the House Committee on Oversight and Government Reform on Avandia risks. Von Eschenbach told the committee the agency had requested the warnings in letters dated May 23. “Although this issue is already prominent in the Warnings section for both drugs, FDA decided to make this request because, despite the existing warnings, these drugs were being prescribed to patients with significant heart failure,” said von Eschenbach.
The hearing, prompted by a meta-analysis of cardiovascular events in Avandia studies authored by Cleveland Clinic’s Dr. Steven Nissen and published in the May 21 issue of the New England Journal of Medicine, also featured testimony by Dr. Nissen and GSK R&D head Dr. Moncef Slaoui.
Under questioning by committee members, von Eschenbach allowed that none of the three large-scale studies on the drug had been designed specifically to address heart risks, but noted that this was not the agency’s chief concern at the time of approval. Committee chairman Rep. Henry Waxman framed the drug as a case study in the need for more expansive postmarket safety surveillance.
The questioning was often pointed, as Democrats pilloried the company and the agency and Republicans suggested collusion between Democrats and Dr. Nissen in an effort to hurt GSK and the FDA (Nissen sought help from a number of Democratic officials in gathering data for his analysis prior to its publication). Republican members also questioned Nissen’s methodology and the reliability of meta-analyses. Democrats inquired on the fate of the FDA press officer who recently circulated an email to journalists challenging Nissen’s credibility (von Eschenbach said a letter of reprimand had been placed in his file) and harped on GSK predecessor SmithKline Beecham’s browbeating of Dr. John Buse, who first raised concerns about Avandia’s cardiovascular effects in 1999. SKB officials told Buse he might be liable for a resulting $4 billion loss in the company’s market capitalization, and he agreed to sign a “clarifying statement” to the investor community and assist SKB in future research into the drug.
Predictably, Democrats also addressed GSK’s consumer advertising of Avandia. Rep. Paul Hodes (D-NH) took issue with the language used in GSK’s newspaper ads defending Avandia, which appeared yesterday, chiding FDA for not requiring that the company use the term “heart attack” for cardiovascular events to make it more accessible to the lay reader.
Meanwhile, US market share for GlaxoSmithKline’s Avandia diabetes drug continues to slip, according to Wall Street investment firm Morgan Stanley.
Avandia and Avandamet had a combined 35.3% share of the TZD drug market in the week ended June 1, down from 37.1% in the prior week, Morgan Stanley analyst Jamie Rubin said in a research note, citing marketing data for new weekly prescriptions provided by IMS Health.
David Pernock, Glaxo’s SVP for pharmaceuticals and vaccines told The Wall Street Journal figures show a 15% to 20% drop in Avandia prescriptions since Dr. Nissen’s paper was published. Pernock said doctors are telling the company they don’t want to switch patients currently taking Avandia to a different drug. But they “might slow off putting new patients on it.”