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FDA approves Cubist’s MRSA-killer Sivextro

By Michael Fitzhugh, Staff Writer

Cubist Pharmaceuticals Inc. gained FDA approval Friday evening for Sivextro (tedizolid phosphate), realizing the first big payoff from its $704 million acquisition of Trius Therapeutics Inc.

The once-daily oxazolidinone antibiotic for treating certain gram-positive bacteria infections, including methicillin-resistant Staphylococcus aureus (MRSA), is one of the first antibiotics approved under the Generating Antibiotic Incentives Now (GAIN) provision of the FDA Safety and Innovation Act and comes at a time when President Barack Obama has proposed more than doubling the funding for antibiotic R&D to combat drug-resistant microbes. (See BioWorld Today, March 6, 2014.)

Sivextro is approved to treat patients with acute bacterial skin and skin structure infections (ABSSSIs) caused by certain susceptible bacteria, including S. aureus, various Streptococcus species, and Enterococcus faecalis. Sivextro is available for intravenous and oral use. It’s the second new antibacterial drug approved by the FDA in the past month to treat ABSSSI. On May 23, the agency approved Durata Therapeutics Inc.' Dalvance (dalbavancin). (See BioWorld Today, May 27, 2014.)

“We are pleased by the FDA approval of Sivextro, which provides a new option for physicians to treat patients with serious bacterial skin infections, including those caused by MRSA,” said Michael Bonney, CEO of Cubist.

Taken together, Cubist estimates patients in the U.S. and Europe account for about 45 million days of therapy for gram-positive infections, such as MRSA. Thomson Reuters Cortellis analyst consensus forecasts Sivextro to achieve U.S. sales of $37 million in 2015, with sales climbing steeply to $231 million by 2019.

Sivextro’s approval and news that the company applied for approval of a second antibiotic Thursday are moving Cubist nearly half-way toward its plan to deliver at least four new antibiotics in support of the Infectious Diseases Society of America’s challenge to drugmakers: Bring 10 new antibiotics to market by 2020.

Despite efforts to incentive the development of antibiotics in the U.S., at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die, according to the Centers for Disease Control and Prevention.

Cubist’s application, which received unanimous support from FDA’s Anti-infective Drugs Advisory Committee in March, was based on positive data from two global phase III studies, ESTABLISH-1 and ESTABLISH-2. The studies showed that a six-day course of Sivextro was acceptably safe and achieved noninferiority with a 10-day regimen of Zyvox (linezolid, Pfizer Inc.) given twice daily.

The company also used the data to seek European approval of Sivextro for the treatment of complicated skin and soft-tissue infections. It expects a decision on that from the European Commission during the first half of 2015.

Cubist expects that Sivextro’s shorter six-day regimen will give it an obvious advantage not only with patients, but also with payers. The drug can be given to patients either intravenously or as a pill and has been proved equally effective in both formulations. Cubists’ executive vice president of research & development and chief scientific officer, Steve Gilman, told BioWorld Today that option provides health care providers important flexibility.

“Physicians need more option in delivery,” said Gilman. “With all the concerns about hospital costs, this is one of the ways patients can be migrated to home therapy.”

Cubist has worldwide exclusive rights to Sivextro, except in North and South Korea, through an exclusive license Trius struck with Dong-A ST Co. Ltd. in January 2007. The Lexington, Mass.-based company also has an agreement with Bayer Pharma AG for the distribution of Sivextro in Japan, China and most other countries in Asia, Africa, Latin America and the Middle East.

Cubist also is studying Sivextro as a treatment for ventilator-associated bacterial pneumonia, a type of lung infection.

Diagnostics on the way?

As investors awaited news of FDA’s decision on Sivextro Friday, Sunnyvale, Calif.-based Cepheid Inc. said it would partner with Cubist, AstraZeneca plc and GlaxoSmithKline plc to develop a rapid diagnostic test that can target multidrug- resistant pathogens and support the appropriate use of antibiotics.

“Antibiotic resistance is a serious health crisis that demands immediate attention,” said Lorianne Masuoka, senior vice president of Clinical Development and Medical Affairs at Cubist and the company’s chief medical officer.  “A comprehensive and targeted approach combining rapid diagnostics with antibiotics will advance efforts to treat the right patients at the right time at the right dose and duration.”

Cubist already markets Cubicin (daptomycin), a treatment for complicated skin and skin structure infections and S. aureus bacteremia, and Entereg (alvimopan), first approved in 2008 to help accelerate the time to upper and lower gastrointestinal recovery following surgeries that include re-connection of the bowel following removal of a resected segment. It also markets Dificid (fidaxomicin) in the U.S. and Canada, for the treatment of Clostridium difficile-associated diarrhea.

The company also reported this week that the FDA accepted for review its new drug application for the investigational gram-negative antibiotic ceftolozane/tazobactam, also known as CXA-201, as a potential treatment for complicated urinary tract infections and complicated intra-abdominal infections. The agency assigned the drug a Dec, 21 PDUFA date. Cubist plans to submit a marketing authorization application for ceftolozane/tazobactam to the European Medicines Agency in the same indications in the second half of 2014. (See BioWorld Today, May 13, 2014.)

Cubist’s shares (NASDAQ:CBST) rose 5.4 percent Friday on anticipation of the approval, closing at $72.24, and gained another 2.4 percent in aftermarket trading following news of Sivextro’s approval.