- First presentation of the OASIS-2 topline results
- Sub-analysis examining efficacy of oral-only omadacycline on lesion size also presented at ECCMID 2018
MADRID, Spain, April 23, 2018 (GLOBE NEWSWIRE) -- Paratek Pharmaceuticals, Inc. (PRTK) announced today that an analysis of microbiology data from OASIS-2, its second Phase 3 study of omadacycline in acute skin infections, found that once-daily monotherapy with oral omadacycline is effective in treating frequently isolated pathogens associated with skin infections, including resistant Staphylococcus aureus (MRSA). These findings were presented at the annual meeting of the European Congress of Clinical Microbiology and Infectious Diseases, ECCMID 2018 in Madrid, Spain.
An additional OASIS-2 sub-analysis showed that treatment with omadacycline led to rapid and continual reduction in lesion size, results that were similar to those observed with linezolid. The topline results from OASIS-2 (Omadacycline Acute Skin and Skin Structure Infections Study), demonstrating the overall efficacy and safety profile of once-daily oral-only omadacycline compared to twice-daily oral-only linezolid in acute bacterial skin and skin structure infections (ABSSSI), were presented for the first time yesterday at the Congress during the “Snapshot on Pre-registration Clinical Trials” oral session.
“The omadacycline clinical data continue to demonstrate the utility of oral-only omadacycline dosing, which would enable treatment of ABSSSI in the outpatient setting and potentially reduce the need for hospital admission,” said Evan Loh, M.D., President, Chief Operating Officer, and Chief Medical Officer, Paratek. “Importantly, we believe the new microbiology data presented show that once-daily, oral-only omadacycline is highly active against multiple pathogens including those with known resistance including MRSA.”
The OASIS-2 study was a randomized, double-blind, multi-center study that enrolled 735 adult subjects with moderate to severe ABSSSI at 33 centers in the U.S. Patients received either once-daily, oral omadacycline or twice-daily, oral linezolid for 7 to 14 days.
Analysis by Infection Type and Pathogen in OASIS-2
To analyze clinical success per infection type in OASIS-2, the modified intent-to-treat (mITT) population included randomized subjects without a sole Gram-negative pathogen(s) at baseline (n=720). Infection type broke down as follows: 59% wound infection; 24% cellulitis/erysipelas, and 18% major abscess. Results at Post Therapy Evaluation (PTE), showed that once-daily monotherapy with oral omadacycline was effective across infection types studied. Efficacy for omadacycline was comparable to linezolid in wound infection (82% vs 77%), cellulitis/erysipelas (88% vs 93%), and major abscesses (84% vs 79%).
Analysis of the micro-mITT population, which included patients with at least one Gram-positive pathogen at baseline (N=563) showed that the most frequently identified pathogens were Staphylococcus aureus (80% overall; 44.4% MSSA and 37.5% MRSA) and Streptococcus anginosus group (18%) with mixed Gram-positive and Gram-negative infections in 12% of the patients. Overall clinical success at PTE for omadacycline in S. aureus was 83% compared to 80% for linezolid (MSSA 81% vs 79% and MRSA 86% vs. 79%), S. anginosus 86% vs. 73%, and mixed infections 78% vs. 82%.
Effect on Lesion Size and Local Signs of ABSSSI
An additional analysis examined the effect of once-daily, oral omadacycline on lesion size and local signs of ABSSSI compared to twice-daily, oral linezolid. In the mITT, subjects without a sole Gram-negative pathogen at baseline were randomized to omadacycline (n=360) or linezolid (n=360). Median baseline lesion area was 322.3 cm2 for omadacycline and 239.9 cm2 for linezolid. The median decrease in lesion size on day 3 was 60.7% for omadacycline and 58.8% for linezolid. At end of treatment evaluation, lesion size had decreased 97.9% for omadacycline and 97.5% for linezolid; at PTE lesions had decreased 100% in both groups.
OASIS-2 Topline Results
In the pivotal, Phase 3 OASIS-2 study, 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. 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 clinically evaluable population were 97.9% vs. 95.5%, respectively.
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. The median duration of nausea was two days and the median duration of vomiting was one day. Additional TEAEs, occurring in ≥ 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.
About Paratek Pharmaceuticals, Inc.
Paratek Pharmaceuticals, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative therapies based upon its expertise in novel tetracycline chemistry. The Company’s lead product candidate, omadacycline, is an investigational new, once-daily oral and intravenous broad-spectrum antibiotic being developed for the treatment of serious community-acquired bacterial infections, including community-acquired bacterial pneumonia (CABP), acute bacterial skin and skin structure infections (ABSSSI), and urinary tract infections (UTI). Omadacycline has been granted Qualified Infectious Disease Product designation and Fast Track status by the U.S. Food and Drug Administration (FDA) for the target indications of ABSSSI, CABP, uncomplicated urinary tract infections (uUTI) and complicated urinary tract infections (cUTI). Paratek’s New Drug Applications have been accepted for priority review by the U.S. FDA and the Company is preparing a marketing authorization in the European Union. Paratek has entered into a collaboration agreement with Zai Lab for the development and commercialization of omadacycline in the greater China region and retains all remaining global rights.
Under a research agreement with the U.S. Department of Defense, omadacycline is also being studied against pathogenic agents causing infectious diseases of public health and biodefense importance, including plague and anthrax.
Paratek's second Phase 3 product candidate, SEYSARA™ (sarecycline), is being developed by Allergan in the U.S. as a new once-daily oral therapy for the treatment of acne. Allergan has completed Phase 3 development activities for SEYSARA and its new drug application was accepted for review by the U.S. FDA in December 2017. Paratek retains all ex-U.S. rights to sarecycline.
Recognizing the serious threat of bacterial infections, Paratek is dedicated to providing solutions that enable positive outcomes and lead to better patient stories.
For more information, visit www.ParatekPharma.com or follow @ParatekPharma on Twitter.
Forward Looking Statements
This press release contains forward-looking statements including statements related to our overall strategy, product candidates, prospects, potential and expected results, including statements about the development, launch and commercialization of omadacycline, the potential for omadacycline to treat ABSSSI, CABP, UTI and other serious community-acquired bacterial infections, the prospect of omadacycline providing broad-spectrum activity, our ability to obtain regulatory approval of omadacycline and our anticipated transition to a commercial stage organization. All statements, other than statements of historical facts, included in this press release are forward-looking statements, and are identified by words such as “potential,” “prospective,” “prepare” and other words and terms of similar meaning. These forward-looking statements are based upon our current expectations and involve substantial risks and uncertainties. We may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in our forward-looking statements and you should not place undue reliance on these forward-looking statements. Our actual results and the timing of events could differ materially from those included in such forward-looking statements as a result of these risks and uncertainties. These and other risk factors are discussed under "Risk Factors" and elsewhere in our Annual Report on Form 10-K for the year ended December 31, 2017, and our other filings with the Securities and Exchange Commission. We expressly disclaim any obligation or undertaking to update or revise any forward-looking statements contained herein.
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