National Editor

Meeting its self-imposed deadline by more than a week, Cubist Pharmaceuticals Inc. submitted the new drug application for injectable Cidecin as a treatment for complicated skin and skin structure infections caused by Gram-positive organisms, including Staphylococcus aureus.

"It's a replacement drug for vancomycin and it's a better drug all around," said Thomas Shrader, an analyst with Gerard Klauer Mattison in New York, which makes a market in Cubist.

The submitted package includes data from two Phase III trials, safety data from several Phase II trials, and safety data from Phase I studies on drug-drug interactions, renally and hepatically impaired subjects and other special populations. In all, the data involve almost 1,800 patients treated with the drug.

Shrader called the package "small but, I think, big enough." He said the FDA "has made so much noise about the need for these [antibacterial] drugs" that the agency is likely to approve Cubist's "unless they can really come up with something" that would disqualify it. Cidecin has proven safe and efficacious once the single, daily dose regimen was established, he noted.

Scott Rocklage, CEO of Lexington, Mass.-based Cubist, said Cidecin (daptomycin) has been tested against about 21,000 clinical bacterial isolates. There are an estimated 500,000 skin and skin structure infections annually in the U.S., and "it's an entry point into many subsets of infections," he added.

Shrader predicted a market launch by late 2003 if expedited review is granted (as he expects) by the FDA and by 2004 if not, with sales of $137 million in the U.S. in 2005.

In trials, "they had to fiddle with the dose for about half the patients on vancomycin, and with none on Cidecin," Shrader said, adding that the condition targeted by the drug is serious.

"These are not children's ear infections," he said. "These are skin infections gone bad, [as in] botched surgeries. You don't look at these pictures during lunch."

Cubist's stock tumbled more than 46 percent at the beginning of the year when Cidecin failed in a Phase III trial against community-acquired pneumonia (CAP), even though that was considered a relatively small market for the drug - an estimated 5 percent to 10 percent of the total, the company said. (See BioWorld Today, Jan. 18, 2002.)

The stock "got crunched a little bit," Shrader acknowledged, as some in the industry said Cubist's management should have foreseen the difficulties in the CAP trial.

"It's hard to go from a $40 to a $4 stock with no commercial changes in the potential of your drug," he said.

Cubist's shares (NASDAQ:CBST) closed Friday at $8.64, down 24 cents, but dipped lower during the fall of this year.

Shrader told BioWorld Today he had "talked to a lot of people, and one guy warned me [the CAP trial] was trickier than people were thinking." His source was the chief medical officer at another company.

"There can be Gram-negative contamination [in CAP patients] and the drug fails because it was never intended for that," Shrader said, although whether that was the case in Cubist's trials is unknown.

Rocklage pointed to another, somewhat ironic problem. He said Cubist "happened to do a fantastic job with ceftriaxone," which is sold as Rocephin by Basel, Switzerland-based F. Hoffmann-La Roche Ltd. and is the standard treatment against which Cidecin was compared. The cure rate was 88 percent for ceftriaxone - previous tests with the drug had only done as well as the low 80s, he said - and 80 percent for Cidecin.

"Eighty percent doesn't sound like a bad number, but the goal of the trial was to demonstrate equivalence," Rocklage said. "We don't know if at higher doses [Cidecin] would do better or not," but the company will make a decision next year on whether to pursue the CAP indication, he said.

"It's not a priority," he said. A key goal in the CAP trial was to gather safety data, which are contained in the NDA submission, he added.

Shrader said he didn't include any sales for Cidecin against CAP in his estimates, but said no safety issues surfaced in the CAP trials that likely would cause the FDA concern, and results were close enough to the comparing therapy, ceftriaxone, that regulators probably would not worry about possible off-label use of Cidecin against CAP.

But Cubist's shares never really recovered from the hit and in September, Foster City, Calif.-based Gilead Sciences Inc. returned European rights to the drug to Cubist, which blamed a disagreement about labeling. Three months later, Gilead disclosed its plan to merge with Triangle Pharmaceuticals Inc., but said that move was unrelated to action taken on Cidecin. (See BioWorld Today, Sept. 11, 2002, and Dec. 5, 2002.)

"The story got too complex for them," Shrader said, and Gilead decided its focus was better directed at antivirals. Rocklage told BioWorld Today that Cubist has made "significant progress" in finding another overseas partner and expects to have news regarding that in the first half of 2003.

The company also has Phase III studies under way with Cidecin in both infective endocarditis/bacteremia and in vancomycin-resistant Enterococcal (VRE) infections. Rocklage said an independent board will review the trial when 30 of the 100 evaluable patients are enrolled in the former trial, probably in mid-2003. He had no estimate when the VRE trial might yield data, saying it's "not a huge project and not a big part" of the plan for Cidecin.