Nabriva Therapeutics AG (NASDAQ:NBRV), a clinical-stage biopharmaceutical company engaged in the research and development of novel anti-infective agents to treat serious infections, with a focus on the pleuromutilin class of antibiotics, today announced research findings for lefamulin, the company's advanced clinical-stage product candidate, were presented at the IDWeek conference, which took place in New Orleans, LA, October 26-30, 2016.
Lefamulin is a semi-synthetic antibiotic Nabriva is developing to be the first pleuromutilin antibiotic available for systemic administration in humans and is the first new class of antibiotic to have reached late stage clinical development for Community Acquired Bacterial Pneumonia (CABP) in over a decade. Nabriva has initiated two global, registrational Phase 3 clinical trials investigating lefamulin treatment in patients with moderate-to-severe CABP and expects top-line data from both CABP phase 3 trials in the second half of 2017.
Findings of the posters being presented at IDWeek 2016™ are as follows:
Population Pharmacokinetic (PPK) Analysis for Lefamulin Using Phase 1 Data and Assessment of Optimal PK Sampling Strategies (OSS) for a Phase 3 Community-Acquired Bacterial Pneumonia (CABP) Study (Poster No. 1944)
L. Zhang, S.M. Bhavnani, P.G. Ambrose, S. Gelone, W.W. Wicha, C.M. Rubino
- The final population pharmacokinetic (PK) model, a three-compartment disposition model with nonlinear protein binding, two parallel first-order absorption processes, and an absorption delay for the second absorption process occurring though multiple transit compartments, provided precise and unbiased fits to lefamulin PK data after IV and PO administration.
- The covariate analyses showed that a high fat/high calorie meal resulted in slower absorption rate compared to those under the fasted condition.
- Results of OSS analyses indicated that a balanced 3- or 4-sample scheme based on fixed sampling windows provided the most accurate estimates of Area Under the Curve (AUC) 0-24 hours.
- Evaluation of an unbalanced scheme indicated that use of the 4-sample fixed window scheme in a clinical trial setting with less than optimal sampling compliance would still result in acceptably precise estimates of lefamulin AUC 0-24 at steady state.
- Application of the population PK model allowed for the identification of OSS, the implementation of which in Phase 3 will allow for pharmacometric evaluations of PK data from patients.
Pharmacokinetic-Pharmacodynamic (PK-PD) Target Attainment Analyses to Support Oral Lefamulin Dose Selection in the Treatment of Patients with Community-Acquired Bacterial Pneumonia (CABP) (Poster No. 1976)
S.M. Bhavnani, L. Zhang, C.M. Rubino, J.C. Bader, S. Gelone, W.W. Wicha, P.G. Ambrose
- Regardless of food intake, percent probabilities of PK-PD target attainment based on the free-drug plasma Area Under the Curve: Minimum Inhibitory Concentration (AUC:MIC) ratio targets associated with a 1-log10 CFU reduction from baseline were ≥95.5% for both Streptococcus pneumoniae and Staphylococcus aureus at MIC values covering ≥99.5% of isolates in North America and the EU for both pathogens.
- These data provide support for lefamulin 600 mg PO q12h for the treatment of patients with CABP and suggest that doses can be administered irrespective of food.
- Results of these pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses are similar to those observed with an IV lefamulin dosing regimen for patients with CABP, which included assessment of pulmonary epithelial lining fluid (ELF) exposures in humans and murine ELF PK-PD targets for efficacy and that demonstrated comparable PK-PD target attainment to that based on plasma exposures.
"We are excited by the growing awareness of lefamulin and recognition that there is an unmet need for novel antibiotics for CABP among key members of the infectious disease clinical community,” said Steve Gelone, Pharm.D., Chief Development Officer of Nabriva. “Our poster presentations at the ID Week meeting represent just a portion of the robust work that supports our lefamulin development program in CABP and we look forward to reporting additional data regarding the lefamulin development program.”
IDWeek 2016TM is the combined annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), and the Pediatric Infectious Diseases Society (PIDS).
About Nabriva Therapeutics AG
Nabriva Therapeutics is a clinical stage biopharmaceutical company engaged in the research and development of novel anti-infective agents to treat serious bacterial infections, with a focus on the pleuromutilin class of antibiotics. Nabriva's medicinal chemistry expertise has enabled targeted discovery of novel pleuromutilins, including both intravenous and oral formulations of its lead product candidate. Nabriva's lead pleuromutilin product candidate, lefamulin, is being developed to be the first systemically available pleuromutilin for human use and is the first new class of antibiotic to reach late stage clinical development for community-acquired bacterial pneumonia (CABP) in over a decade. Nabriva believes lefamulin is well positioned for use as a first-line empiric monotherapy for the treatment of moderate to severe CABP due to its novel mechanism of action, targeted spectrum of activity, resistance profile, achievement of substantial drug concentration in lung tissue and fluid, oral and IV formulations and favorable tolerability profile. Nabriva also intends to further pursue the development of lefamulin for additional indications, including the treatment of acute bacterial skin and skin structure infections, and is developing a formulation of lefamulin appropriate for pediatric use.
Nabriva owns exclusive, worldwide rights to lefamulin, which is protected by composition of matter patents issued in the United States, Europe and Japan.
Forward Looking Statements
Any statements in this press release about future expectations, plans and prospects for Nabriva, including but not limited to statements about the development of Nabriva’s product candidates, such as plans for the design, conduct and timelines of Phase 3 clinical trials of lefamulin for CABP, the clinical utility of lefamulin for CABP and Nabriva’s plans for filing of regulatory approvals and efforts to bring lefamulin to market, the development of lefamulin for additional indications, the development of additional formulations of lefamulin, plans to pursue research and development of other product candidates, and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “likely,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and conduct of clinical trials, availability and timing of data from clinical trials, whether results of early clinical trials or trials in different disease indications will be indicative of the results of ongoing or future trials, uncertainties associated with regulatory review of clinical trials and applications for marketing approvals, the availability or commercial potential of product candidates including lefamulin for use as a first-line empiric monotherapy for the treatment of moderate to severe CABP, the sufficiency of cash resources and need for additional financing and such other important factors as are set forth under the caption "Risk Factors" in Nabriva’s annual report on Form 20-F as filed with the United States Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Nabriva’s views as of the date of this release. Nabriva anticipates that subsequent events and developments will cause its views to change. However, while Nabriva may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Nabriva’s views as of any date subsequent to the date of this release.