Grassley Questions FDA About Risks to Children, Infants in Antibiotic Drug Trials

GRASSLEY QUESTIONS FDA ABOUT RISKS TO CHILDREN, INFANTS IN ANTIBIOTIC DRUG TRIALS

Sen. Chuck Grassley today asked the Food and Drug Administration to explain what it is doing to inform parents about the safety concerns surrounding pediatric trials of the Ketek antibiotic

Grassley said he posed the same question of the nation's drug safety agency six weeks ago but hasn't gotten an answer yet. He said he was repeating his inquiry based on a New York Times story today that revealed experts' concerns about these trials involving children and infants. "The adverse events identified with Ketek are serious ones and the possibility that any six-month old child is being exposed to these kinds of risks unnecessarily is unconscionable," Grassley wrote in a letter to Acting Commissioner Andrew C. von Eschenbach.

Grassley's oversight of the Food and Drug Administration began in 2004 over the agency's reluctance to allow information to become public about the risks of pediatric use of certain anti-depressants. He has put pressure on the Food and Drug Administration to make administrative changes to improve its transparency and post-market surveillance of drugs, in addition to introducing legislation to make these kinds of reforms.

The text of Grassley's June 8 and April 27 letters to von Eschenbach follow here.

June 8, 2006

Andrew C. von Eschenbach, M.D.
Acting Commissioner
U.S. Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857

Dear Dr. von Eschenbach:

The United States Senate Committee on Finance ("Committee") has jurisdiction over the Medicare and Medicaid programs and, accordingly, a responsibility to the more than 80 million Americans who receive health care coverage, including prescription drugs, under those programs.

I read with great interest and concern today's New York Times article entitled, "Halt Is Urged for Trials of Antibiotic in Children," regarding the recommendations of officials in the Office of Drug Safety ("ODS") at the Food and Drug Administration ("FDA" or "the agency") and a consult conducted by Dr. Danny Benjamin, an infectious disease specialist at Duke University. I understand that Dr. Benjamin was asked by the FDA to examine the pediatric trials.

According to the article, a recent internal review of safety reports by ODS officials found 110 cases of liver problems (liver failure and serious liver injury) associated with telithromycin ("Ketek"), since the antibiotic was approved in April 2004. It is alarming that most of these serious events occurred in otherwise healthy people. Based on their review, these officials recommended that the FDA "consider forcing Sanofi-Aventis [the manufacturer of Ketek] to withdraw Ketek from the market, severely restrict its uses, even in adults, or add a prominent warning to its label about potentially fatal side effects."

The New York Times further reports that in light of the risk of fatal liver failure, blurred vision and loss of consciousness, Dr. Rosemary Johann-Liang, an FDA official in ODS, questioned the agency's decision to allow pediatric trials of Ketek to proceed. She also questioned whether or not it was possible to assess blurred vision and loss of consciousness in very young children. In his separate consult, the article reports that Dr. Benjamin also "concluded that the pediatric trials with Ketek were a cause for concern and 'hard to support.'"

My concern about the safety risks to infants and children was first expressed to you in my letter of April 27, 2006. Now my concerns are even further heightened by the New York Times article on ODS's assessment of adverse events associated with Ketek and Dr. Johann-Liang's and Dr. Benjamin's conclusions regarding the pediatric trials.

Let me reiterate that more than 6 weeks ago I asked you to advise the Committee of "what action has been taken to fully inform the parents of infants and children enrolled in this study about the risks and benefits of Ketek." Unfortunately, I have not received a response to this important question, and I presume that parents who have enrolled their children in the trials have not been advised of anything either.

Accordingly, as Chairman of the Committee, I request that the FDA respond to the following immediately:

1. Describe the current efforts by the agency to provide parents and patients with updated safety information regarding Ketek and specify the timeframe for implementation of these efforts. If there are no plans to update consent forms and patient brochures at this time, please provide a rationale for the FDA's decision.

2. A search of the ClinicalTrials.gov website shows that Sanofi-Aventis has three ongoing trials in children ages 6 months to 13 years, "TELI COM - Telithromycin in Children With Otitis Media," "TELI TON - Telithromycin in Tonsillitis," and "Comparative Study to Evaluate the Efficacy and Safety of Telithromycin Given Once Daily Versus Cefuroxime Axetil Given Twice Daily in Children With Middle Ear Infections," and a fourth trial involving adolescents 13 years of age and older, "TELI TAD - Telithromycin in Tonsillitis in Adolescents and Adults." Is the FDA considering temporary suspension of these trials until the serious concerns and issues related to Ketek are resolved?

3. Please make available Dr. Rosemary Johann-Liang for an interview with my Committee staff no later than June 28, 2006. Please ensure that Dr. Johann-Liang is provided with a copy of this letter and have your staff contact my staff by no later than June 12, 2006, to make arrangements for the interview.

Thank you for your attention to this very important matter. I look forward to hearing from you regarding my questions and concerns immediately. The adverse events identified with Ketek are serious ones and the possibility that any six-month old child is being exposed to these kinds of risks unnecessarily is unconscionable.

Sincerely,

Charles E. Grassley
Chairman

http://grassley.senate.gov/index.cfm?FuseAction=PressReleases.Detail&PressRelease_id=5092&Month=6&Year=2006