Paratek Release: Consistent Efficacy And Safety Profile Observed In New Analyses Of OASIS-1 Phase III Study Of Omadacycline In Patients With Difficult To Treat Comorbid Conditions
Published: Oct 06, 2017
- No dosing adjustment anticipated in these special populations
SAN DIEGO, Oct. 06, 2017 (GLOBE NEWSWIRE) -- Paratek Pharmaceuticals (Nasdaq:PRTK) announced the results of three sub-analyses from the Phase 3 OASIS-1 study that show a consistent safety and efficacy profile of its once-daily oral and intravenous (IV), broad-spectrum investigational antibiotic, omadacycline, when treating Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in patients with comorbid conditions, which could be associated with reduced treatment efficacy and increased safety-related adverse events. These data will be presented tomorrow, October 7, at IDWeek 2017 in San Diego.
The analyses compared omadacycline to linezolid in subsets of ABSSSI patients enrolled in the global Phase 3 registration study with: chronic kidney disease; high body mass index; diabetes, and a history of intravenous drug users with or without hepatitis C infection. In addition to omadacycline demonstrating a consistent efficacy and safety profile compared to linezolid, these data suggest that no dose adjustments for omadacycline are required in patients with these comorbid conditions.
“These data demonstrate that dosing adjustments should not be required for patients with comorbid conditions such as impaired renal function, diabetes or a high body mass index, and support our confidence that omadacycline has the potential to offer physicians the convenience of a fixed-dose, well-tolerated, once-daily, oral and IV antibiotic option in patients with community-acquired skin infections,” said Evan Loh, M.D., President, Chief Operating Officer, and Chief Medical Officer, Paratek. “As we look towards FDA approval and commercialization, the ongoing analyses of our clinical data continue to bolster our confidence in omadacycline’s potential to address the significant health challenge of antibiotic resistance, even in patients where their comorbid conditions can make it more challenging to treat their infections.”
OASIS-1 (Omadacycline in Acute Skin Structure Infections Study) evaluated the efficacy and safety of IV-to-oral once-daily omadacycline against twice-daily linezolid over a 7 to 14-day course of therapy in 645 treated patients. The primary efficacy endpoint for the FDA was early clinical response (ECR) at 48 to 72 hours after the first dose of study drug in the modified intent-to-treat (mITT) population (patients without a potentially causative monomicrobial gram-negative infection). In the mITT analysis population, omadacycline achieved the primary efficacy endpoint of statistical non-inferiority (10% margin) compared to linezolid. The ECR for the omadacycline and linezolid treatment arms was 84.8% compared to 85.5%, respectively.
Additionally, the FDA-specified secondary endpoint was the investigator assessment of response at the post treatment evaluation (PTE) visit (7-14 days after the completion of therapy) in both the mITT population (86.1% for omadacycline vs. 83.6% for linezolid) and in the clinically evaluable (CE) population (96.3% for omadacycline vs. 93.5% for linezolid).
- Omadacycline in Chronic Kidney Disease with ABSSSI: In this safety analysis, 522 patients had stage 0/1 chronic kidney disease (CKD-0/1), 119 had stage 2/3 chronic kidney disease (CKD-2/3). Response rates at ECR assessment were slightly higher in patients with CKD-0/1 in the omadacycline group (87.4%) compared to patients with CKD-2/3 (82.3%). Similarly, for patients treated with linezolid, ECR rates were 87.1% and 83.7% for CKD-0/1 and CKD-2/3, respectively.
PTE responses in the mITT population were 87.0% for omadacycline vs. 84.8% for linezolid in CKD-0/1 patients. In patients with CKD-2/3, rates were 90.3% vs. 85.7% for omadacycline and linezolid, respectively. PTE responses in the CE population were 96.7% for omadacycline vs. 94.4% for linezolid in CKD-0/1 patients, and 94.7% for omadacycline vs. 91.1% for linezolid in patients with CKD-2/3.
Overall, omadacycline was safe and generally well tolerated in patients with CKD, with similar AEs to subjects without CKD. Overall, the safety and efficacy of omadacycline in patients with CKD-0/1 and CKD-2/3 was similar to that observed in the general population. TEAEs were comparable between omadacycline and linezolid treatment.
- Omadacycline in Diabetic and Obese Patients with ABSSSI: In the sub-analyses comparing omadacycline to linezolid in patients with high BMI, evaluable patients had elevated BMI of =25 (n=417). Of those, 225 were overweight (25 < BMI <30) and 192 were obese (BMI > 30); irrespective of BMI, 59 patients had a medical history of diabetes.
Omadacycline outcomes were comparable at ECR assessments in patients with normal (BMI <25) and high BMI. Outcomes in the high-BMI omadacycline treatment group were comparable to outcomes in the linezolid treatment group for the primary endpoint in the mITT (84.8% vs. 85.9%). At PTE, high BMI omadacycline-treated patients showed higher clinical success than linezolid-treated patients (85.9% vs. 83.4%) in the mITT population. PTE response in the high BMI CE population were 95.8% for omadacycline vs. 93.1% for linezolid.
At PTE, in both the mITT and CE populations, omadacycline-treated diabetic patients showed higher clinical success compared to linezolid-treated diabetic patients. Overall, the safety and efficacy of omadacycline was consistent regardless of BMI or diabetes diagnosis.
- Omadacycline in ABSSSI Patients with a History of IV Drug Use (IVDU) and Hepatitis C (HCV+): In this analysis, 322 patients were IVDU and 168 were IVDU/HCV+. ECR rates were comparable for both omadacycline and linezolid in both IVDU and non-IVDU patients, regardless of HCV diagnosis. PTE responses with omadacycline were higher than linezolid in non-IVDU patients in both the mITT and clinically evaluable (CE) populations. For both omadacycline and linezolid, clinical success at PTE tended to be lower among IVDU and IVDU/HCV+ patients, compared with the non-IVDU and non-IVDU/HCV- patients in the mITT populations. The lower clinical success observed among IVDU and IVDU/HCV+ patients was due to the greater number of indeterminate responses (e.g. lost to follow-up, withdrew consent). Tolerability was similar across all patient groups, with no major differences in liver function.
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 a 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. Omadacycline has been granted Qualified Infectious Disease Product designation and Fast Track status by the U.S. Food and Drug Administration for the target indications of ABSSSI, CABP, uUTI and cUTI. Paratek has completed Phase 3 development activities for omadacycline in CABP and ABSSSI and is preparing to submit marketing applications in the United States and European Union. Paratek has licensed rights for omadacycline to Zai Lab for the greater China region, and retains all remaining global rights.
Under a research agreement with the U.S. Department of Defense, omadacycline also is 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, 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 sarecycline and is preparing a new drug application for submission to the U.S. Food and Drug Administration. 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, clinical studies, prospects, potential and expected results, including statements about the timing of advancing omadacycline and otherwise preparing for clinical studies, the timing of enrollment in our clinical studies and our reporting of the results of such studies, the potential for omadacycline to serve as an empiric monotherapy treatment option for patients suffering from ABSSSI, CABP, UTI, and other bacterial infections when resistance is of concern, the prospect of omadacycline providing broad-spectrum activity, and our ability to obtain regulatory approval of omadacycline All statements, other than statements of historical facts, included in this press release are forward-looking statements, and are identified by words such as "advancing," "believe," "expect," "well positioned," "look forward," "anticipated," "continued," 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, 2016, 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.
|Media Relations:||Investor Relations:|
|Michael Lampe||Hans Vitzthum|
|(484) 575-5040||LifeSci Advisors, LLC.|