Cubist Pharmaceuticals Incorporated is seeking approval from the Food and Drug Administration (FDA) for expanded use of its drug Cubicin. The drug received FDA approval in 2003 to treat skin infections, and Cubist is hoping to extend the approval to fight bacteremia, or bacteria in the blood, as well as heart-valve inflammation caused by staph infections.

Cubist, based in Massachusetts, said expanded approval would be beneficial because a resistant staph infection in the heart valve is one of the hardest to treat. Drug-resistant staph infections can spread to a patient's heart, bones, lungs and bloodstream. By 2002, more than half of the staph bacteria found in US hospitals were resistant to conventionally prescribed antibiotics, including methicillin, penicillin and amoxicillin.

Cubist began Cubicin's trial testing in 2002, but had trouble recruiting patients with the heart-valve problem in question, called endocarditis. Cubist was also unsuccessful at recruiting enough patients with bacteremia. When the trial ended in 2005, only 53 of the 235 participants had confirmed endocarditis. After the trial, Cubist announced that the results of the study surpassed expectations. FDA staff reviewer Alfred Sorbello, however, was skeptical.

Out of the 19 patients in the trial diagnosed with an infection in the right heart valve, eight were successfully treated. For those with a left-valve infection, only one out of nine was successful. Older drugs worked in seven out of 16 patients with right-side infections, and two out of nine with left-side infections.

Dr. Sorbello said analyzing such a small sample was like asking a baseball manager to assess a rookie who got six hits in his first 20 chances at bat, suggesting the possibility that Cubist got lucky with the results. Without more data, he said, the trial was "insufficient to draw any meaningful inferences." In addition, he was worried about persisting infections in six patients in the trial, two who later died, who took Cubicin and then developed a strain of bacteria that was less susceptible to the drug.

In March 2006, Cubist received approval for Cubicin to be used for bacteremia, but not for endocarditis. Michael Booney, Cubist's chief executive, argued that a trial with enough endocarditis patients to meet the highest statistical standard for proving a drug's equivalence to older treatments would take so much time and money that it would never happen. He also said evidence of about Cubicin shows the drug is effective against endocarditis.

On May 5, 2006, Dr. Janice Soreth, chief of the anti-infectives division of the FDA, overruled Sorbello and other reviewers and approved Cubicin for patients with endocarditis. She also noted that doctors were already using the drug for endocarditis without FDA approval.

Source: Anna Wilde Mathews, "Inside FDA, a battle over drug to treat "Darth Vader" bacteria," Wall Street Journal, December 1, 2006.