- Pooled analysis from Phase 2 and truncated Phase 3 studies demonstrates comparable safety and efficacy profiles for omadacycline compared with linezolid
- Single dose randomized trial demonstrates that omadacycline has no effect on QTc interval
AMSTERDAM, Netherlands, April 11, 2016 (GLOBE NEWSWIRE) -- Paratek Pharmaceuticals, Inc. (Nasdaq:PRTK) today presented data from two clinical studies that reinforce the safety and clinical activity of omadacycline. Data from a pooled analysis of a Phase 2 study and a truncated Phase 3 study in patients with complicated skin and skin structure infections (cSSSI) showed that omadacycline appeared comparable to linezolid in evaluations of safety and efficacy. Data from a separate, single-dose study showed that omadacycline had no impact on QTc interval. Full data from these studies were presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Amsterdam. Paratek is a biopharmaceutical company focused on the development and commercialization of innovative therapies based upon tetracycline chemistry.
“The data presented today strengthen a growing body of evidence supporting the potential clinical efficacy and a favorable safety profile of IV and oral once daily omadacycline in serious bacterial skin infections, particularly where resistance is of concern to treating physicians,” said Evan Loh, President and Chief Medical Officer, Paratek. “Our focus now is to continue to execute on our ongoing Phase 3 clinical program, which will enable approval of omadacycline and thus, its availability for patients who would benefit from a broad spectrum antibiotic that covers resistant pathogens.”
Data were pooled from a Phase 2 and a truncated Phase 3 study (Poster #P1326) comparing the safety and efficacy of once-daily omadacycline to twice-daily linezolid in patients with complicated skin and skin structure infections. The Phase 3 study enrollment was truncated after a change in the industry-wide FDA regulatory guidance regarding the primary endpoint for serious skin infections which occurred during the conduct of the study.
In each study, patients were randomized 1:1 to receive either omadacycline or linezolid therapy. For patients randomized to omadacycline, they were initially treated with once-daily omadacycline 100 mg by intravenous injection (IV), followed by an option to step-down to a once a day 300 mg oral dose (determined to be bioequivalent to the 100 mg IV dose) in the Phase 3 study or a 200 mg oral once-daily dose in the Phase 2 study. Patients in the linezolid group were treated with twice-daily linezolid 600 mg IV, with the option to transition to twice-daily 600 mg oral linezolid. Both studies were conducted in a double-blinded fashion. For all patients step-down to oral was based upon clinical response to IV and the expectation that improvement would continue.
Clinical success was defined as having completed treatment with resolution of the infection without recrudescence of the infection upon completion of study follow-up. Across both studies, 377 patients were randomized to either omadacycline or linezolid. Of these, 359 were included in the intent to treat and safety populations (omadacycline=179; linezolid=180) and 315 were deemed clinically evaluable (omadacycline=160; linezolid=155). For the intent to treat population, clinical success rates for both arms were comparable, with 87.2% (156) in the omadacycline treatment arm achieving clinical success compared with 81.1% (146) of those receiving linezolid. For the clinically evaluable population, clinical success occurred in 156 (97.5%) patients on omadacycline compared to 146 (94.2%) on linezolid. Rates of reported adverse events were also comparable for both arms; gastrointestinal adverse events were most frequent (28.5% for omadacycline and 26.1% for linezolid). Five patients in the omadacycline arm and three in the linezolid arm discontinued treatment due to adverse events.
A separate healthy volunteer clinical study was designed in accordance with FDA guidance for a Thorough QTc (TQTc) study in order to evaluate for any omadacycline effects on cardiac repolarization. This study evaluated the primary endpoint of omadacycline’s effect on the QTc interval (Poster #P1321) as measured by a surface electrocardiogram (ECG). Sixty-four (64) subjects in the study were randomized received either 100 mg or 300 mg doses of IV omadacycline, 400 mg of oral moxifloxacin, or placebo. Subjects underwent a baseline ECG prior to first treatment. After dosing, subjects were monitored continuously for 24 hours with serial ECGs and omadacycline concentrations were measured at set time points for 96 hours. Omadacycline demonstrated no prolongation of QTc at either dose at any time point following administration. Omadacycline did not increase QTcF1 as demonstrated by one-sided 95% upper confidence bounds on placebo-and baseline-adjusted QTcF (ddQTcF) at all post-dose time points. The largest values observed for omadacycline were 1.53 milliseconds for the 100 mg dose at six hours and 0.83 milliseconds for the 300 mg dose at two hours. Assay sensitivity was demonstrated by observing that the maximal mean increase in ddQTcF by moxifloxacin exceeded 8 milliseconds and also that the increase in ddQTcF by moxifloxacin was greater than 5 milliseconds at multiple time points. There was no relationship between omadacycline plasma concentrations and ddQTcF. Consistent with the known and specific antagonistic effect of omadacycline on the human M2 subtype of the muscarinic receptor, a mean maximal increase in heart rate of 17 bpm (omadacycline 100 mg) and 24 bpm (omadacycline 300 mg) were observed within one hour of dosing, compared to an increase in 3 bpm for placebo and 5 bpm for moxifloxacin. Heart rate increases were determined to be of short duration, asymptomatic, peaking at one-hour post dose and becoming comparable across all groups by 12 to 24 hours post-dose. Omadacycline was not associated with any clinically significant changes in either systolic or diastolic blood pressure. These results are consistent with preclinical data, which suggest that omadacycline has a low potential for cardiac arrhythmia or any other clinically significant cardiovascular adverse events.
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. Paratek's lead product candidate, omadacycline, is the first in a new class of tetracyclines known as aminomethylcyclines, with broad-spectrum activity against Gram-positive, Gram-negative and atypical bacteria. Paratek initiated a Phase 3 registration study in ABSSSI in June 2015 to determine the efficacy and safety of omadacycline compared to linezolid. The completion of enrollment in the ABSSSI trial was announced on April 4, 2016. Top-line data from this study is expected to be available as early as the end of June. A Phase 3 registration study for CABP comparing omadacycline to moxifloxacin was initiated in November 2015 and top line data is expected in the second half of 2017.
Omadacycline is a new once-daily oral and IV, well-tolerated broad-spectrum antibiotic being developed for use as empiric monotherapy for patients suffering from serious community-acquired bacterial infections, such as acute bacterial skin and skin structure infections, community acquired bacterial pneumonia, urinary tract infections (UTI), and other community-acquired bacterial infections, particularly when antibiotic resistance is of concern to prescribing physicians.
Paratek's second Phase 3 product candidate, sarecycline, is designed to be a well-tolerated, once daily, oral, narrow spectrum tetracycline-derived antibiotic with potent anti-inflammatory properties for the potential treatment of acne and rosacea in the community setting. Allergan owns the U.S. rights for the development and commercialization of sarecycline. Paratek retains all ex-U.S. rights. Allergan initiated two identical Phase 3 registration studies in December 2014 for sarecycline for the treatment of moderate to severe acne vulgaris.
For more information, visit www.paratekpharma.com.
Forward Looking Statement
Certain statements in this press release, including statements regarding the projected availability of top-line data from Paratek's Phase 3 clinical trials of omadacycline and the expected benefits of Paratek's product candidates are forward-looking statements. These forward-looking statements are based upon Paratek's current expectations and involve substantial risks and uncertainties. Paratek may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in these forward-looking statements and you should not place undue reliance on these forward-looking statements. 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, which include, without limitation, risks related to (i) unexpected results that may cause the designs of the clinical trials to change, or the projected timelines of the trials to be extended, (ii) unexpected decline in the rates of patient enrollment in the clinical trials, (iii) unforeseen adverse effects experienced by patients resulting in a clinical hold, (iv) failure of patients to complete clinical trials, (v) risks related to regulatory oversight of the trials, (vi) the need for substantial additional funding to complete the development and commercialization of product candidates and (vii) risks that data to date and trends may not be predictive of future results. These and other risk factors are discussed under "Risk Factors" and elsewhere in Paratek's Annual Report on Form 10-K for the year ended December 31, 2015 and Paratek's other filings with the Securities and Exchange Commission. Paratek expressly disclaims any obligation or undertaking to update or revise any forward-looking statements contained herein.
1 A formula that accounts for the physiologic shortening of the QTc interval that occurs as the heart rate increases, enabling a comparison of the QTc interval across a range of rates