Paratek Pharmaceuticals has announced positive top-line results from a global, pivotal phase 3 clinical study comparing its once-daily oral and IV, broad spectrum investigational antibiotic, omadacycline, to moxifloxacin in the treatment of patients with community-acquired bacterial pneumonia (CABP). This study represents the second positive phase 3 registration study of omadacycline, which will be used to support marketing applications to the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

“This successful study demonstrates the potential of omadacycline to treat community-acquired bacterial pneumonia, a significant and serious health issue,” said Michael Bigham, Chairman and Chief Executive Officer at Paratek. “This phase 3 study in pneumonia along with our previously announced successful Phase 3 study in skin infections satisfy the regulatory filing requirements of our special protocol assessment with the FDA. We look forward to sharing these data with the FDA and EMA. Our plan is to submit our NDA in the US as early as the first quarter of 2018 with an EMA submission later in 2018.”

The global, pivotal Phase 3 clinical study known as OPTIC (Omadacycline for Pneumonia Treatment in the Community), compared the safety and efficacy of once-daily, IV-to-oral omadacycline to IV-to-oral moxifloxacin for treating adults with CABP. In the study, 774 patients were randomized. Omadacycline met the FDA-specified primary endpoint of statistical non-inferiority (NI) in the intent-to-treat (ITT) population (10% NI margin, 95% confidence interval) compared to moxifloxacin at the early clinical response (ECR) 72-120 hours after initiation of therapy. The ECR rates for the omadacycline and moxifloxacin treatment arms were 81.1 % and 82.7%, respectively.

Additionally, the FDA-specified secondary endpoints evaluated omadacycline at the post treatment evaluation (PTE) visit 5-10 days after the completion of therapy in both the ITT population (87.6% for omadacycline vs. 85.1% for moxifloxacin) and in the clinically evaluable (CE) population (92.9% for omadacycline vs. 90.4% for moxifloxacin) as determined by investigators. The secondary endpoints also achieved statistical non-inferiority.

The co-primary endpoints for the EMA were non-inferiority in the ITT and CE CABP populations in those patients with Pneumonia Severity Index (PORT) III and IV at the PTE time point. Omadacycline demonstrated a high response rate and met statistical non-inferiority to moxifloxacin for both populations using a prespecified 97.5% confidence interval. High success rates were observed with response rates of 88.4% (omadacycline) vs. 85.2% (moxifloxacin) and 92.5% (omadacycline) vs. 90.5% (moxifloxacin), respectively.

“We now have experience with omadacycline in more than 1,500 patients in our clinical program and we are very pleased with the safety, tolerability, and efficacy profile that we have seen to date,” said Evan Loh, M.D., president, chief operating officer, and chief medical officer at Paratek. “We are deeply indebted to the patients, investigators, and entire Paratek team for their commitment to advancing omadacycline. We are delighted to have achieved this significant milestone for the program and the company as we work to bring omadacycline to patients.”

In the study, omadacycline was generally safe and well tolerated, consistent with prior studies of omadacycline. The most common treatment emergent adverse events (TEAEs) in omadacycline-treated patients (occurring in > 3% of patients) were ALT increase (3.7% with omadacycline vs. 4.6% with moxifloxacin) and hypertension (3.4% with omadacycline vs. 2.8% with moxifloxacin). Gastrointestinal adverse events of interest for omadacycline vs. moxifloxacin included: vomiting (2.6% vs. 1.5%), nausea (2.4% vs. 5.4%), and diarrhea (1.0% vs. 8.0%), respectively. There were no cases of clostridium difficile colitis or infection in patients treated with omadacycline, compared with seven cases (1.8%) in patients treated with moxifloxacin.

Rates of TEAEs were 41.1% for omadacycline vs. 48.5% for moxifloxacin. Drug-related TEAEs were 10.2% for omadacycline vs. 17.8% for moxifloxacin. Discontinuation for TEAEs was uncommon, 5.5% for omadacycline vs. 7.0% for moxifloxacin. Serious TEAEs occurred in 6.0% of omadacycline patients and 6.7% of moxifloxacin patients; four of these were considered related to study drug, two for omadacycline and two for moxifloxacin. The mortality rate was 2.1% with omadacycline and 1.0% with moxifloxacin. Drug-related serious TEAEs leading to premature discontinuation of test article were 2.6% with omadacycline and 2.8% with moxifloxacin.

“Community-acquired bacterial pneumonia results in approximately 3.3 million hospitalizations in the United States each year with a significant mortality risk of more than 5 percent seen in observational studies, putting a significant burden on the healthcare system,” said Dr. Thomas M. File Jr., M.D., MS, Chair of the Infectious Disease Section, Northeast Ohio Medical University, and Chair of the Infectious Disease Division, Summa Health. “Antibiotic resistance is a national issue as susceptibility rates have decreased across most antibiotics since 2010, underscoring the need for new, effective therapies. The positive top-line results of omadacycline in community-acquired bacterial pneumonia is welcome news.”