FDA Advisors Back Two Antibiotics for ABSSSIs
Anti-Infective Drugs Advisory Committee votes unanimously for Dalvance and Sivextro
The FDA’s Anti-Infective Drugs Advisory Committee voted unanimously to recommend approval of two antibiotics for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).
Dalvance (dalbavancin, Durata Therapeutics) for injection was supported in a 12–0 vote, while Sivextro (tedizolid phosphate, Cubist Pharmaceuticals) was recommended 14–0. The FDA often follows its committees’ recommendations, although it is not bound by them.
The new drug application (NDA) for Dalvance was accepted for priority review by the FDA in November 2013 with an action date of May 26, 2014. If approved by the FDA, dalbavancin would be the first once-weekly antibiotic for ABSSSI, providing an alternative to current once- or twice-daily treatments.
Twenty-one clinical trials have been conducted with dalbavancin, including five phase III trials evaluating nearly 3,000 patients. Two phase 3 trials, DISCOVER 1 and DISCOVER 2 (Dalbavancin for Infections of the Skin COmpared to Vancomycin at an Early Response), included more than 1,300 patients with ABSSSIs.
Dalbavancin is a second-generation, semi-synthetic lipoglycopeptide that consists of lipophilic side-chains attached to glycopeptides. It would require two once-weekly 30-minute intravenous (IV) doses (1,000 mg on Day 1 and 500 mg on Day 8). Dalbavancin demonstrates bactericidal activity in vitro against a broad range of bacteria, including MRSA strains, Streptococcus pyogenes, and certain other streptococcal species.
Tedizolid phosphate is a once-daily oxazolidinone being developed for both IV and oral administration. Cubist’s NDA is based on positive data from two global phase III clinical studies. The NDA for Sivextro has been assigned priority review with an action date of June 20, 2014.
Tedizolid phosphate 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.
ABSSSIs increased by 176% from 1997 to 2009 in hospitalized patients. The majority of skin and soft tissue infections in such patients are caused by Staphylococcus aureus, and an estimated 59% of these infections are caused by MRSA in the U.S.