Successful Phase III OASIS-2 study of omadacycline to treat ABSSSI- Paratek Pharmaceuticals

Paratek Pharmaceuticals, Inc. announced positive top-line results from a pivotal Phase III clinical study comparing its once-daily, oral investigational antibiotic, omadacycline, to twice-daily oral linezolid in the treatment of acute bacterial skin and skin structure infections (ABSSSI). The study met all of its primary and secondary endpoints required to support approval for this indication by the FDA and the European Medicines Agency (EMA). This represents the third positive Phase III registration study of omadacycline.

The pivotal Phase III clinical study known as OASIS-2 (Omadacycline in Acute Skin Structure Infections Study) evaluated the efficacy and safety of once-daily, oral-only omadacycline compared to twice-daily, oral-only linezolid in 735 adults with ABSSSI. Omadacycline met the FDA-specified primary endpoint of statistical non-inferiority (NI) in the modified intent-to-treat (mITT) population (10% NI margin, 95% confidence interval) compared to linezolid at the early clinical response (ECR), 48 to 72 hours after the first dose of study drug. The ECR rate for omadacycline was 87.5% compared to 82.5% for linezolid. Additionally, omadacycline met statistical NI compared to linezolid for the EMA-specified co-primary endpoints at the post therapy evaluation (PTE), 7 to 14 days after completion of therapy in the mITT and the Clinically Evaluable (CE) populations.

Clinical success rates at PTE in the mITT population for the omadacycline and linezolid arms were 84.2% vs. 80.8%, respectively; and in the CE population were 97.9% vs. 95.5%, respectively. Omadacycline demonstrated high clinical success rates for infections caused by the most common ABSSSI pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). In the OASIS-2 study, there was a low rate of study treatment discontinuation for both omadacycline and linezolid patients at 10.9% vs. 14.2%, respectively. Less than 2% of patients discontinued treatment due to adverse events in both treatment groups. No deaths occurred in the omadacycline treatment arm. The most common treatment emergent adverse events (TEAEs) in omadacycline and linezolid treated patients were nausea (30.2% vs. 7.6%, respectively) and vomiting (16.8% vs. 3.0%, respectively). Seventy-five percent of the nausea was classified as mild with none reported as severe, and only one omadacycline patient discontinued treatment for gastrointestinal events. The vast majority of the onset of the nausea or vomiting in omadacycline patients occurred during the loading-dose phase on day 1 or day 2, and the median duration of these episodes was two days. Additional TEAEs, occurring in more than 3% of omadacycline patients were increased alanine aminotransferase (ALT; 5.2%), increased aspartate aminotransferase (AST; 4.6%), diarrhea (4.1%) and headache (3.5%), which were generally comparable between treatment arms. No subject in either treatment group developed Clostridium difficile infection.

Comment: There are already a number of drugs on the market for these resistant infections, but most are narrowly focused and taken through an IV route, whereas omadacycline is being developed both as an IV treatment and a daily pill, which could give it an edge in administration.