FDA Advisory Committee recommends approval of Cubist’s Sivextro

In the unanimous 14 – 0 decision, the AIDAC found that substantial evidence of the safety and effectiveness of SIVEXTRO for the treatment of acute bacterial skin and skin structure infections (ABSSSI) was provided.

SIVEXTRO is a once daily oxazolidinone being developed for both intravenous (I.V.) and oral administration for the treatment of serious infections caused by certain Gram-positive bacteria, including those caused by methicillin-resistant Staphylococcus aureus (MRSA).

The company’s New Drug Application (NDA) submission to the FDA for SIVEXTRO is based on positive data from two global Phase 3 clinical studies, which met the primary and secondary endpoints defined by the FDA and European Medicines Agency (EMA).

Cubist Pharmaceuticals chief scientific officer and research and development executive vice president Dr Steven Gilman noted that the company is very pleased with the strong endorsement from AIDAC members, and recommendation of approval for tedizolid, now known in the US as SIVEXTRO.

"We are encouraged by the recognition that there is a need for more treatment options for patients to address serious skin infections. We look forward to the FDA’s final review of SIVEXTRO and decision," Dr Gilman added.

The AIDAC recommendation is not binding on the FDA, but will help inform the FDA as it completes its Priority Review of the NDA for SIVEXTRO, which has an assigned action date of June 20, 2014.

Additionally, the EMA recently accepted for review the company’s marketing authorization application (MAA) for the investigational antibiotic, for which Cubist is seeking approval for the treatment of complicated skin and soft tissue infections (cSSTI).

A decision from the European Commission is expected during the first half of 2015.

Tedizolid phosphate (formerly TR-701), now known in the US as SIVEXTRO, is a novel oxazolidinone antibiotic drug candidate that is rapidly converted in vivo by phosphatases to the microbiologically active moiety TR-700.

TR-700 acts by binding to the bacterial 50S ribosomal subunit thereby inhibiting protein synthesis. Tedizolid is being developed for both I.V. and oral administration in the potential treatment of ABSSSI, also referred to as cSSTI.

Tedizolid is also being investigated for potential use in nosocomial pneumonia (hospital-acquired bacterial pneumonia [HABP] and ventilator-associated bacterial pneumonia [VABP]). Two Phase 3 studies, conducted in the US, Europe and other regions worldwide, in ABSSSI and cSSTI demonstrated that tedizolid 200mg once daily for six days was statistically non-inferior to 10 days of linezolid 600mg twice daily for the primary efficacy endpoints. Secondary endpoints were also met.

In these studies, the adverse event rates were similar for both tedizolid and linezolid treated patients. Gastrointestinal adverse events (diarrhea, nausea and vomiting) were the most commonly reported in both treatment groups.