Doribax Trial Ended Early Due To Death Rate

Drug maker Johnson & Johnson just ended a Doribax trial early over increased risk of death and reduced cure rates in pneumonia patients. Drugmaker Shionogi & Co. of Japan, manufactures Doribax.

Doribax (doripenem) is approved in the United States for the treatment of adults diagnosed with complicated urinary tract or abdominal infections; the drug is not approved for any type of pneumonia, the Food and Drug Administration (FDA) said, wrote Reuters. In Europe, Doribax is approved for hospital-acquired pneumonia. The halted trial was being conducted as part of a post-marketing mandate from the European Medicines Agency (EMA), said Shaun Mickus, spokesman at Janssen, the Johnson & Johnson unit that markets the drug, said Reuters.

The trial was testing the use of Doribax in pneumonia patients who were also receiving ventilator treatment, an approved European use, said Bloomberg Businessweek, which noted that the agency indicated that Doribax is considered safe and effective for the uses for which it is approved in the U.S.

The halted study involved 274 people and the closedown recommendation came from an independent monitoring committee, said Shaun Mickus, a company spokesman, said Businessweek. Mickus would not say why Doribax failed, but the firm said doctor and patient advice for the drug remains unchanged. “The bottom line is Doribax is safe and effective when used according to its approved label,” Mickus told Businessweek in a telephone interview.

In the trial, Doribax patients died 21.5 percent of the time, versus 14.8 percent in the control group treated with different medications, said the FDA. Also, the agency noted that Doribax patients were cured of pneumonia 45.6 – 49.1 percent of the time, versus 56.8 – 66.1 percent in the control group, wrote Businessweek.

This translates into, said Reuters, a 6.7 percent-increased rate of death from any cause versus patients receiving an alternative treatment. Also Doribax patients had an 11.2 percent decreased rate for cure than patients taking a different drug.

The trial, which was halted in May, involved several study sites worldwide, including in the U.S. In June 2007, Johnson & Johnson applied for U.S. approval of Doribax to treat hospital-acquired pneumonia, also known as nosocomial pneumonia, which includes ventilator-associated pneumonia, Reuters explained. In November 2008, the agency requested more information on the drug and, said Mickus, it resubmitted its applications and discussions are ongoing.

An FDA safety announcement informed the public that the recent Doribax trial was halted early over significant safety concerns, including excess mortality and numerically poorer clinical cure rates in patients treated with Doribax versus patients treated with the drug, imipenem-cilastatin, said PharmaLive.

Doribax is still considered safe and effective for its approved indications—treatment of adults with complicated intra-abdominal infections and urinary tract infections, including pyelonephritis. The recommended dose of Doribax—for adults—is 500 mg every eight hours intravenously, with the dose administered over one hour and for between five and 14 days, depending on indication, said PharmaLive.