Cubist reports positive Phase III trial results of Sivextro

The results will also appear in a forthcoming print issue of the journal. The authors note that ESTABLISH-2 was the first prospectively designed clinical trial consistent with the fundamental elements outlined in the final US Food and Drug Administration (FDA) ABSSSI Guidance released in 2013.

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 published data are based on one of the two global Phase 3 clinical studies of Sivextro (ESTABLISH-1 and ESTABLISH-2), which met the primary and secondary endpoints defined by the FDA and European Medicines Agency (EMA). The clinical trials enrolled 1,333 people in the U.S., Europe and other regions worldwide.

As outlined in The Lancet Infectious Diseases, a focus of the ESTABLISH-2 clinical trial was to evaluate the efficacy and safety of the I.V. to oral transition of Sivextro in the treatment of ABSSSI.

The randomized, controlled Phase 3 clinical trial compared Sivextro 200 mg given as a once daily dose for six days with linezolid 1200 mg divided as a twice daily dose for 10 days, both administered by I.V. with a possible switch to oral study treatment, when pre-specified criteria were met. Results showed a six-day course of once-daily Sivextro to be non-inferior to 10 days of twice-daily linezolid for the treatment of ABSSSI.

In the ESTABLISH-2 study, the adverse event rates were similar for both Sivextro and linezolid treated patients. Gastrointestinal adverse events (diarrhea, nausea and vomiting) were the most commonly reported in both treatment groups.

"Publication of ESTABLISH-2 clinical trial results in The Lancet Infectious Diseases contributes important information to the infectious disease community worldwide about Sivextro," said Steven Gilman, Ph.D., Executive Vice President of Research and Development and Chief Scientific Officer of Cubist Pharmaceuticals.

"These data provide further support for the potential of Sivextro as a novel treatment option that might be used in the transition from I.V. to oral therapy in a short, six-day course of treatment for patients with serious skin infections."

Data from the ESTABLISH-2 study, along with data from the previously published ESTABLISH-1 study, served as the basis for Cubist’s New Drug Application (NDA) for Sivextro, for which Cubist is seeking approval in acute bacterial skin and skin structure infections (ABSSSI).

The FDA accepted the NDA in December 2013 for Priority Review, assigning a Prescription Drug User Fee Act (PDUFA) action date of June 20, 2014. On March 31, 2014 the FDA Anti-Infective Drug Advisory Committee (AIDAC) voted unanimously to recommend approval of Sivextro.

The Company also recently announced that the EMA accepted for review its Marketing Authorization Application (MAA) for Sivextro, for which Cubist is seeking approval for the treatment of complicated skin and soft tissue infections (cSSTI).