New superbug treatment Sivextro approved in US

Cubist's Sivextro, a new weapon in the war against antibiotic-resistant infections, has been approved in the US.

Novel antibiotics are desperately needed, as 'superbug' bacteria which are resistant to standard treatments are becoming increasingly common. This risks the clock turning back to the early 20th century before the advent of antibiotics, when deaths from everyday infections were commonplace.

There are many barriers to the discovery and development of new antibiotics, including lack of market incentives for pharma companies to launch new products. The US and Europe have now put in place a number of incentives and joint-working initiatives to help accelerate the development of promising candidates.

Sivextro (tedizolid phosphate) is a novel oxazolidinone to treat susceptible Gram-positive pathogens including MRSA, one of the most notorious superbugs.

There are an estimated 80,000 severe MRSA infections and 11,000 deaths from MRSA in the US evey year, according the country's Centers for Disease Control and Prevention (CDC).

Sivextro is now licensed for adult acute bacterial skin and skin structure infections (ABSSSI). Available in intravenous (IV) and oral formulations, the drug is taken once a day for six days.

This is one of the key therapeutic and commercial benefits of the drug over existing treatments, which must be taken for longer, and can only be taken intravenously, and therefore require hospital treatment.

Generating Antibiotic Incentives Now (GAIN)

The drug is one of the first medicines approved in the US that the FDA designated as a Qualified Infectious Disease Product (QIDP) for its indication, ABSSSI, according to the Generating Antibiotic Incentives Now (GAIN) Act of 2012. The QIDP designation qualifies Sivextro for incentives including a five year extension of patent exclusivity.

Sivextro's approval was supported by two Phase 3 studies, which showed that it was statistically non-inferior to 600 mg of Pfizer's Zyvox (linezolid) taken twice a day for 10 days. In these studies, the adverse event rates were similar for patients treated with Sivextro and linezolid. Gastrointestinal adverse events (diarrhoea, nausea and vomiting) were the most commonly reported in both treatment groups.

The company, based in Lexington, Massachusetts is one of the few companies with an extensive pipeline of new antibiotics, and around 75% of its R&D resources are focused on the therapy area, amounting to $400 million this year.

Cubist's chief executive Michael Bonney says it is aiming to launch at least four new antibiotics by 2020, which will contribute to the goal of the Infectious Diseases Society of America (IDSA) for 10 new antibiotics to be available in this time.

"MRSA is still problematic in the US and is responsible for the deaths of more than 11,000 Americans each year," said Ralph Corey, M.D., Professor of Medicine and Infectious Disease, Duke Clinical Research Institute and Duke University Medical Center. "Not every antibiotic will work for every patient and more drug options are an imperative. Physicians should evaluate the use of Sivextro. A six-day course of therapy with the option to choose - and, if needed - change from IV to oral administration is a welcome new development."

Senator Richard Blumenthal (D-CT), who introduced the GAIN legislation in the US, commented on the approval.

"I am proud to have introduced the GAIN Act, which is one important piece of addressing the public health crisis of untreatable infections and drug-resistant pathogens. "Today's announcement shows that we are starting to see new products enter the market – which is a promising step in addressing these life-threatening conditions. I look forward to working with my colleagues on other initiatives to continue the fight against deadly antimicrobial resistance."

Peak sales forecast

The drug will compete with Pfizer's existing treatment, Zyvox (linezolid) which earned $346 million in global sales in 2013, as well as the generic vancomycin.

Sivextro's more convenient once daily dosing for six days compares favourably with the Zyvox regimen of twice a day for 10 days, and with vancomycin, which must be taken several times a day.

It is envisaged that most patients will begin treatment on Sivextro intravenously at a hospital and then 'stepped down' to a pill form which they can take at home.

There are signs that the regulatory incentives are beginning to help drugs reach the market. The first new product approved under the FDA's QIDP system was Durata Therapeutics' Dalvance, which won approval in May. Dalvance is licensed to treat the same serious skin infections as Sivextro, but can only be administered intravenously.

Based on these market dynamics, analyst predict Cubist's drug could reach peak annual sales of $300 million and upwards.

In Europe, the EMA has accepted for review Cubist's marketing authorisation application for Sivextro, for which the company is seeking approval for use against complicated skin and soft tissue infections (cSSTI). A decision from the European Commission is expected during the first half of 2015. Clinical studies are also ongoing for use of the drug in treating hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP).

The FDA has just accepted another new drug application from Cubist - ceftolozane/tazobactam for the treatment of complicated urinary tract Infections and complicated intra-abdominal infections. The drug has been accepted as a Priority Review and the FDA expects to publish its ruling on 21 December.