Cubist Pharmaceuticals Inc. said its investigational antibiotic, Cidecin, failed to meet its primary endpoint in the first of two pivotal Phase III trials for community-acquired pneumonia.
The news sent Lexington, Mass.-based Cubist’s stock (NASDAQ:CBST) tumbling 46.4 percent Thursday, falling $14.73 to close at $17.02.
Cubist Chairman and CEO Scott Rocklage told BioWorld Today the company’s next move will be to work with the FDA in evaluating the data from the CAP I study and to determine the best course of action. The company had projected a third-quarter new drug application filing.
Rocklage said the FDA is the “primary gatekeeper” for pursuing this strategy.
As to how the news affects the company overall, Rocklage said, “It’s one Phase III trial within a collection of Phase III trials. When you develop antibiotics you often pursue multiple indications.”
Rocklage said the stock’s nosedive was simply a matter of “investors absorbing the news.”
“We also had expectation that it would succeed in all regions of the world, but we did not meet the endpoint in international,” Rocklage said.
He said the company remains strong. Cubist had $93 million in cash as of Sept. 30 and raised $165 million in the fourth quarter, bringing the pro forma total to $258 million.
The company had two Phase III trials under way simultaneously, known as CAP I and CAP II.
In the first study of 714 patients, Cidecin, or daptomycin for injection, failed to demonstrate equivalence as defined by a 10 percent or less decrease in achievement in the resolution of signs and symptoms in the intent-to-treat population to the comparator agent, Rocephin (ceftriaxone sodium). The evaluable patients demonstrated a clinical success rate of 79 percent and the ceftriaxone arm demonstrated an 87 percent clinical success rate.
Rocklage emphasized during a conference call to announce the news that the North American population showed more improvement with Cidecin than ceftriaxone, or 72 percent compared to 62 percent in the intent-to-treat population. The success rate in clinically evaluable patients in North America and Western Europe was 85 percent for Cidecin and 84 percent for ceftriaxone.
However, patients in Eastern Europe, including Russia, who made up two-thirds of the patient enrollment, did not respond well. South Africa was also among the study sites.
“At this point, we do not have a cogent hypothesis as to why Eastern Europe failed,” Rocklage said.
One important finding of the study, he said, is that Cidecin’s safety profile is similar to ceftriaxone’s. One of the goals of the study, Rocklage said, was to build a safety database for Cidecin beyond two other successful Phase III trials in preparation for submitting the NDA.
In light of these results, Cubist has suspended the CAP II study, which was being conducted in Eastern Europe, South America and Latin America.
Cubist’s senior vice president of drug development, Bob McCormack, said it is not uncommon to see different results in different geographical regions, including in the antibiotic area.
“But people have worked through it and gotten plans back on track,” McCormack said.
Cidecin also has been studied for complicated skin and soft-tissue infection (cSST), successfully showing safety and efficacy in two pivotal Phase III trials.
Cubist had planned to file a new drug application with the FDA in the third quarter of this year. The fact that Cidecin failed for community-acquired pneumonia (CAP) does not compromise the company’s planned filing for cSST. Rocklage said there will be continuing discussions with the FDA to ascertain whether it makes sense to go forward with the NDA during the previously scheduled time frame, and also whether it would be for the one cSST indication or also for CAP.
“That’s the next decision point for the company,” he said.
Thomas Dietz, of Pacific Growth Equities in San Francisco, said in a research note that “the uncertainty in the timeline for Cidecin is based upon whether it makes economic sense to launch Cidecin into just the cSST marketplace.”
“This information will become more apparent as Cubist performs their stated market research plan to canvass physicians and formularies to determine their potential view of Cidecin in light of the CAP results,” Dietz wrote.
Cubist has a strategic alliance with Gilead Sciences Inc., of Foster City, Calif., for marketing the product in Europe, an agreement entered into in January of last year. This agreement covers all of the European Union plus Switzerland. The company is in negotiations for an Asian alliance, Rocklage said. (See BioWorld Today, Jan. 9, 2001.)
“My impression is that Gilead remains very, very supportive of daptomycin for the European market,” Rocklage said.
Community-acquired pneumonia, while important, is not a major part of the overall marketing strategy, Rocklage said, noting that some analysts have estimated CAP would make up only 5 percent to 10 percent of the potential market for Cidecin.
Cubist will be studying Cidecin intravenously for endocarditis in a Phase III trial scheduled to begin this quarter. There also is a Phase II trial under way for complicated urinary tract infection.
And there is an ongoing Phase III trial for vancomycin-resistant enterococci infections, which was begun in the fall.
In another area, Albany Molecular Research Inc., of Albany, N.Y., and Cubist entered a research and licensing agreement for the discovery of a new class of anti-infective drugs designed to break through the resistance of stubborn microorganisms in August. (See BioWorld Today, Aug. 21, 2001.)
In August 2000, Cubist acquired TerraGen Discovery, of Vancouver, British Columbia, for $29 million in stock. (See BioWorld Today, Aug. 9, 2000.)
TerraGen’s technology included methods to collect environmental samples and clone large DNA samples to create its NatGen collection of organisms that produce novel compounds. In addition, the company’s chemical extract library, called NatChem, also could be screened as drug candidates.
Syrrx Inc., of San Diego, signed its first deal when it formed an anti-infective drug discovery collaboration with Cubist in June. (See BioWorld Today, June 28, 2001.)