By Lisa Seachrist
Cubist Pharmaceuticals Inc. initiated a pivotal study of daptomycin, the company¿s rapidly acting antibiotic for the treatment of life-threatening infections.
The Cambridge, Mass.-based company will test the new antibiotic in trials in the U.S. and Europe as a treatment for complicated skin and soft tissue infections caused by Gram- positive bacteria strains ¿ the major players in hospital-based infections ¿ including antibiotic-resistant strains.
In addition to the Phase III studies, the company is also exploring the drug¿s use in treating bacteremia, or bloodstream infections, in a Phase II dosing study.
¿We feel very lucky to be developing such an important drug,¿ said Scott Rocklage, president and CEO of Cubist. ¿The FDA embraced the strategy of finding new therapies for life-threatening infections, and we are working with them to move this product quickly.¿
Daptomycin is naturally occurring antibiotic that is produced during fermentation by streptomyces bacteria. The drug was originally discovered by Eli Lilly and Co., of Indianapolis, in the late 1980s, during soil screening assays. The drug is a rapidly active bactericide that kills all Gram-positive bacteria. Lilly began clinical development on the molecule and tested the drug in 300 patients before shelving its development in 1991.
Cubist licensed the intravenous drug from Lilly in 1997 and raised $14 million in September 1998 to steer it through Phase III studies. The FDA granted fast-track status, and approved the company¿s plan to test the drug as a therapy for complicated skin infections; soft-tissue infections, such as wound infections; and burns.
The Phase III clinical trials in the U.S. and Europe will each enroll 400 patients ¿ 200 to be treated with 4 milligrams per kilogram of body weight of daptomycin intravenously once every 24 hours, for up to 14 days. The 200 patients in each control group will receive vancomycin or either nafcillin or oxacillin, which represent the current standard of care for serious resistant bacterial infections.
The primary endpoint for the study will be clinical outcome, as determined by disappearance of signs and symptoms. Secondary endpoints of efficacy will be bacteriological eradication, and time to reduce body temperature to normal levels.
¿We are measuring the time to reduce body temperature to get a comparison of how quickly daptomycin gives a clinical result,¿ Rocklage said. ¿If you look at the time course for killing bacteria, daptomycin is much faster than vancomycin. Vancomycin takes 8 to 10 hours to kill the same number of bacteria that daptomycin kills in 40 to 50 minutes. Theoretically, daptomycin should provide a clinical result faster.¿
The company is testing the drug against vancomycin because it is the drug of last resort for patients who have developed antibiotic resistant bacterial infections. Every year, more than 200,000 hospitalized patients develop a complicated skin infection or soft-tissue infection following surgery, intravenous drug administration and ulcerated skin conditions. Many of these infections are resistant to a number of antibiotic therapies.
Cubist is also testing the drug in a Phase II study of bloodstream infections. Patients with bloodstream infections not associated with endocarditis will receive either 4 milligrams per kilogram of body weight or 6 milligrams per kilogram intravenously once a day, or the control drugs vancomycin, or either nafcillin or oxacillin. The primary endpoint will be bacterial eradication from the bloodstream. Secondary endpoints will include 28-day mortality; time to sterilization of the blood; and time to reduce temperatures to normal levels.
Other Infections Targeted Soon
¿We will be looking at other indications in the future including pneumonia; osteomyelitis, which is a bone infection; and hospital-based, urinary-tract infections,¿ Rocklage said.
Rocklage said the company hopes to conclude the pivotal trials in both the U.S. and Europe in the first or second quarter of 2000, and file a new drug application in the first quarter of 2001.
Cubist¿s stock (NASDAQ:CBST) closed Monday at $3.687, down $0.125. n