LEXINGTON, Mass.—A new treatment for some of the most antibacterial-resistant infections has edged closer to the end of the drug pipeline. Cubist Pharmaceuticals, a biopharmaceutical company focused on therapies for the acute-care environment, recently submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) following positive results from Phase 3 clinical trials of ceftolozane/tazobactam. The drug was shown to be effective at treating both complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI).
“We’re thrilled with the results and believe these two trials provide a strong basis for approval from the FDA and the European Medicines Agency,” Dr. Steve Gilman, chief scientific officer at Cubist, tells DDNews. “The data show that ceftolozane/tazobactam could be effective against extremely difficult- to-treat Gram-negative pathogens in cUTI and cIAI.”
Cubist conducted one trial of ceftolozane/tazobactam with 1,000 patients with cUTI and another trial with 1,000 patients with cIAI. Data from the two trials, which Cubist presented at the 2014 European Congress of Clinical Microbiology and Infectious Disease in Barcelona, Spain, revealed that the drug was effective at eradicating three pathogens that are common causes of cUTI and cIAI: Pseudomonas aeruginosa, extended-spectrum beta-lactamas-producing Escherichia coli (E. coli) and Klebsiella pneumoniae. “We found that 84 percent to 100 percent of the pathogens were eradicated by ceftolozane/tazobactam in our trials of cUTI and cIAI,” Gilman says. “These results met primary endpoints that were agreed upon with the FDA and European Medicines Agency.”
Ceftolozane/tazobactam is made up of two drugs. Ceftolozane is a novel drug that has demonstrated potent activity against Pseudomonas aeruginosa. Tazobactam is a commonly used lactamase inhibitor that is known to be safe and effective. Cubist added tazobactam to ceftolozane to broaden the range of pathogens against which its antibiotic is effective.
Ceftolozane/tazobactam could move especially swiftly towards commercialization due to its status as a Qualified Infectious Disease Product (QIDP) under the Generating Antibiotic Incentives Now (GAIN) Act, a 2012 law that enables the FDA to provide incentives to encourage the development of new antibiotics. The FDA granted the antibiotic candidate Fast Track status under the Gain Act in 2013, allowing a significant reduction in the amount of time it will take the FDA to review Cubist’s NDA. Cubist expects a decision from the FDA by the end of December. If approved, ceftolozane/tazobactam’s QIDP status could also qualify it for a five-year extension of the exclusivity provided through the Hatch-Waxman Act.
The GAIN Act was enacted as a response to the growing urgency surrounding the threat of antibiotic resistant bacteria. A widespread consensus within the medical research community has emerged regarding the need to develop new, effective antibiotic therapies to replace those vulnerable to drug-resistant bacteria. A recent World Health Organization (WHO) effort focusing on this problem specifically highlights the need to develop antibiotics for the treatment of urinary tract infections caused by E. coli—one of the pathogens targeted by ceftolozane/tazobactam. Without the development of such new antibiotics, notes Dr. Keji Fukda, WHO’s assistant director-general for health security, the world could be “headed for a post-antibiotic era, in which common infections and minor injuries, which have been treatable for decades, can once again kill.”
Cubist has remained focused on the development of new antibiotics during a period when the overall antibiotic pipeline has contracted. “There’s been a general lack of research and development in novel antibacterials at same time that antibacterial resistance is increasing,” Gilman notes. “We are one of the companies that has stayed the course and remained focused on developing antibiotics that combat increasing antimicrobial resistance and rising hospital-acquired infections.” Cubist plans to invest $400 million this year in R&D directed toward antibiotic treatments.
The company is also waiting for FDA approval of another antibiotic candidate, Sivextro, which is designed to treat bacterial skin infections. “If things go well, we could have two antibiotics approved for the U.S. market this year,” Gilman says. An FDA advisory panel recently issued a unanimous recommendation for Sivextro’s approval, and a final decision is expected in June.
Cubist sees the potential for ceftolozane/tazobactam to be developed into a commercial drug with market reach rivaling the company’s most successful drug to date, Cubicin. “We think this is a billion-dollar opportunity worldwide, with roughly the same-sized market opportunity as Cubicin,” says Gilman. Cubist is also developing ceftolozane/tazobactam as a potential treatment for hospital-acquired bacterial pneumonia.