A Food and Drug Administration advisory committee will decide Friday whether to recommend that a widely used but controversial antibiotic be removed from the market.
The drug, known as Ketek, is used to treat respiratory tract infections such as bronchitis, sinusitis, and pneumonia. U.S. Doctors have written an estimated 6 million prescriptions for the drug since it was approved in April, 2004.
But FDA is revisiting that approval in two days of expert hearings Thursday and Friday because of reports suggesting the drug could carry a higher risk of liver failure and other dangerous side effects than similar antibiotics.
The hearings also come one day after a Senate committee investigation blasted agency officials for their handling of Ketek’s original approval.
Ketek was never shown to be more effective than other antibiotics at curing most infections. FDA requires only that new antibiotics show evidence of “non-inferiority” to existing drugs. The rationale, experts say, is to help ensure a steady stream of available drugs to combat antibiotic resistance.
The drug was judged to be as safe as other antibiotics when it was approved in 2004, based on pre-market studies.
“Ketek is being (targeted) because of the safety concerns that have arisen,” said John Jenkins, director of FDA’s Office of New Drugs.
Sanofi Aventis, which manufactures Ketek, reported to FDA 212 cases of liver injury in patients who took the drug over the last two-and-a-half years. However, company and agency experts characterize the reports as initial signals of both minor and severe injuries that cannot be reliably blamed on the drug.
The company argued Thursday that the injuries occurred over 6 million uses of Ketek, and that the drug, known generically as telithromycin, carries about the same overall risk as similar antibiotics.
“Take your pick of antibiotics, they are all associated with liver injury,” said James Lewis, a professor of Medicine at Georgetown University who testified on behalf of the company.
But an analysis commissioned by the agency found 35 cases of severe injuries ncluding seven resulting in a liver transplant or death that analysts say were very likely attributable to Ketek.
“What we have is a higher number of these hospitalized patients” than are seen with other drugs, said William Lee, director of the Clinical Center for Liver Diseases at the University of Texas Southwestern and one of the analysts commissioned by FDA.
The advisory committee is scheduled Friday to consider other data linking Ketek to more side effects, including temporary blindness and abnormal heart rhythms.
But the meeting is taking place against a backdrop of stark criticism from the Republican chairman of the Senate Finance Committee, which has spent the last year investigating FDA’s handling of Ketek’s approval.
A committee report released Wednesday concluded that FDA officials did not tell the advisory panel that recommended Ketek’s approval in 2003 that unethical practices by some doctors conducting Sanofi Aventis’ safety study had corrupted the trial.
Instead, FDA officials presented the study, called “3014,” to the committee as usual, the report found.
“In sum, the FDA did not ensure that the public received accurate, science-based information regarding the Ketek (application),” Sen. Charles Grassley, R-Iowa, wrote in the report.
On the other hand, FDA officials have said they did not take the flawed study into account when they approved Ketek. They instead relied on European safety studies, attempting to measure Ketek’s safety on the market in France, Germany, and other countries.
Jenkins, who leads the FDA division in charge of approving new drugs, said he had not yet digested the 53-page report.
“I don’t want to get into the details of that today,” he told reporters.
Controversy surrounding Ketek’s approval is also bringing harsh criticism from inside the agency.
David Graham, a scientist in FDA’s Office of Drug Safety, wrote a brief article in the New England Journal of Medicine in November condemning agency officials for resorting to overseas postmarket safety studies to approve Ketek in 2004. Such data is generally considered far less reliable than controlled studies like the discredited 3014 trial.
In addition, Ketek has shown little benefit for patients with sinusitis and bronchitis, who usually get better without any medication, he added.
In an interview, Graham called the hearings an example of “damage control” over Ketek safety issues that have come back to haunt FDA.
“They’ve built a house of cards with no foundation in fact or even in truth,” he said.
Jenkins did not comment on the decision to present the European data to the panel in 2004.
However, he did say that the absence of additional safety issues in 4 million European patients made the officials “comfortable making the decision for approval.”