Nabriva Therapeutics plc (NASDAQ: NBRV), a biopharmaceutical company engaged in the commercialization and development of innovative anti-infective agents to treat serious infections, announced today that Open Forum Infectious Diseases, an official journal of the Infectious Diseases Society of America (IDSA), has published results from a post-hoc analysis of clinical data from patients who initiated treatment in the hospital from the pivotal Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Phase 3 clinical trials. The analyses indicate that lefamulin results in a rapid and similar time to clinical response, a proxy for hospital “discharge readiness,” compared to moxifloxacin.
“There is a clear need for new antibiotics for patients with CABP that result in similar real-world outcomes as fluoroquinolones without the safety concerns,” said Dr. Thomas Lodise, PharmD, PhD Albany College of Pharmacy and Health Sciences and lead author of the study. “Lefamulin has been shown to be non-inferior to moxifloxacin in the treatment of adults with CABP in two, multi-national clinical trials. The current analyses demonstrate that hospitalized adults with CABP treated with lefamulin achieve discharge readiness criteria rapidly. Given the safety concerns with the fluoroquinolones, these results add to the growing body of evidence that lefamulin should be considered as a potential monotherapy replacement for respiratory fluoroquinolones.”
In the post-hoc analysis, investigators examined pooled data of 926 inpatients from the LEAP trials; 468 patients were treated with lefamulin and 458 were treated with moxifloxacin. The analysis evaluated three outcomes among the study population: time to clinical response, time to clinical stability, and time to clinical improvement.
Of the 926 patients included, investigators were able to assess time to clinical response in 918, clinical stability in 925, and clinical improvement in 923. Analyses demonstrated that time to clinical response was nearly identical in both treatment groups, with a median (interquartile range) time from treatment initiation to clinical response of 4 (3-4) days for lefamulin and 4 (3-5) days for moxifloxacin. The median time from treatment initiation to clinical stability or clinical improvement was 3 (2-4) days in both the lefamulin and moxifloxacin groups.
Given the association between time to clinical response and readiness for hospital discharge in patients with CABP, the findings support the potential of lefamulin as an effective IV and oral short-course, monotherapy for CABP that may enable early discharge.
“In the treatment of hospitalized patients with CABP, length of stay is the primary driver of the cost of care,” said Dr. Lodise. “Innovative antibiotics, such as lefamulin, that are safe and efficacious, and are shown to result in a rapid time to clinical response are critical to providing the most cost-effective and highest quality care to our patients.”
XENLETA™ is a first-in-class pleuromutilin antibiotic approved by the U.S. Food and Drug Administration (FDA) for the treatment of community-acquired bacterial pneumonia. It is available in IV and oral formulations enabling initiation of treatment in the hospital, transitioning to outpatient setting or initiating treatment in the community. XENLETA has a novel mechanism of action that targets a binding site on bacteria that is different from existing antibiotics which has been shown to result in no cross resistance to other antibiotic classes commonly prescribed for CABP and a low potential for the development of resistance.
Full results of the post-hoc analysis of LEAP trials data is included in the paper titled: Post Hoc Assessment of Time to Clinical Response Among Adults Hospitalized with Community-Acquired Bacterial Pneumonia Who Received Either Lefamulin or Moxifloxacin in Two Phase III Randomized, Double-Blind, Double-Dummy Clinical Trials, published in Open Forum Infectious Diseases, April 24, 2020.
Pneumonia is an infection of the lung that can be serious and fatal, especially among older adult patients with comorbidities. There are approximately five million cases of pneumonia in the U.S. each year, and pneumonia is the fifth leading cause of hospitalization and one of the leading causes of infection-related death. Streptococcus pneumoniae is the most common cause of bacterial pneumonia in the U.S. According to recent data from the SENTRY Antimicrobial Surveillance Program, in the U.S., approximately 30 to 60 percent of S. pneumoniae, depending on region, are macrolide resistant. In addition to macrolides, fluoroquinolones are another common treatment option for CABP. This broad-spectrum class is an effective option; however, fluoroquinolones carry boxed warnings for several significant safety concerns.
XENLETA (lefamulin) is a first-in-class semi-synthetic pleuromutilin antibiotic for administration in humans discovered and developed by the Nabriva Therapeutics team. It is designed to inhibit the synthesis of bacterial protein, which is required for bacteria to grow. XENLETA’s binding occurs with high affinity, high specificity and at molecular sites that are different than other antibiotic classes. Efficacy of XENLETA was demonstrated in two multicenter, multinational, double-blind, double-dummy, non-inferiority trials assessing a total of 1,289 patients with CABP. In these trials, XENLETA was compared with moxifloxacin and in one trial, moxifloxacin with and without linezolid. Patients who received XENLETA had similar rates of efficacy as those taking moxifloxacin alone or moxifloxacin plus linezolid. The most common adverse reactions associated with XENLETA include diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. For more information, please visit www.xenleta.com.
About Nabriva Therapeutics plc
Nabriva Therapeutics is a biopharmaceutical company engaged in the commercialization and development of innovative anti-infective agents to treat serious infections. Nabriva Therapeutics received U.S. Food and Drug Administration approval for XENLETA (lefamulin), the first pleuromutilin antibiotic for community-acquired bacterial pneumonia (CABP). Nabriva Therapeutics is also developing Contepo™ (fosfomycin) for injection, a potential first-in-class epoxide antibiotic for complicated urinary tract infections (cUTI), including acute pyelonephritis. For more information, please visit https://www.nabriva.com.
INDICATION AND IMPORTANT SAFETY INFORMATION
XENLETA is a pleuromutilin antibacterial indicated for the treatment of adults with community-acquired bacterial pneumonia (CABP) caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of XENLETA and other antibacterial drugs, XENLETA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
IMPORTANT SAFETY INFORMATION
XENLETA is contraindicated in patients with known hypersensitivity to XENLETA or pleuromutilins.
XENLETA tablets are contraindicated for use with CYP3A4 substrates that prolong the QT interval.
WARNINGS AND PRECAUTIONS
XENLETA has the potential to prolong the QT interval. Avoid XENLETA in patients with known QT prolongation, ventricular arrhythmias, and patients receiving drugs that may prolong the QT interval.
Based on animal studies, XENLETA may cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception.
Clostridium-difficile associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including XENLETA, with severity ranging from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs.
The most common adverse reactions (≥2%) for (a) XENLETA Injection are administration site reactions, hepatic enzyme elevation, nausea, hypokalemia, insomnia, and headache and (b) XENLETA Tablets are diarrhea, nausea, vomiting, and hepatic enzyme elevation.
USE IN SPECIFIC POPULATIONS
In patients with severe hepatic impairment, reduce the dosage of XENLETA Injection to 150 mg infused over 60 minutes every 24 hours. XENLETA Tablets are not recommended in patients with moderate or severe hepatic impairment due to insufficient information to provide dosing recommendations.
Avoid XENLETA Injection and Tablets with concomitant strong or moderate CYP3A or P-gp inducers. Monitor for reduced efficacy of XENLETA.
Avoid XENLETA Tablets with strong CYP3A or P-gp inhibitors.
Monitor for adverse reactions of sensitive CYP3A substrates administered with XENLETA Tablets.
XENLETA has not been studied in pregnant women. Verify pregnancy status in females prior to initiating XENLETA and advise females to use contraception during treatment and for 2 days after the final dose. Lactating women should pump and discard milk for the duration of treatment with XENLETA and for 2 days after the final dose.
To report SUSPECTED ADVERSE REACTIONS, or administration during pregnancy, contact Nabriva Therapeutics US, Inc. at 1-855-5NABRIVA or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see Full Prescribing Information for XENLETA.
Any statements in this press release about future expectations, plans and prospects for Nabriva Therapeutics, including but not limited to statements about its ability to successfully launch and commercialize XENLETA for the treatment of CABP, including the availability of and ease of access to XENLETA through major U.S. specialty distributors, marketing exclusivity and patent protection for XENLETA, the development of CONTEPO for cUTI, the clinical utility of XENLETA for CABP and of CONTEPO for cUTI, plans for and timing of the review of regulatory filings for CONTEPO, efforts to bring CONTEPO to market, the market opportunity for and the potential market acceptance of XENLETA for CABP and CONTEPO for cUTI, the development of XENLETA and CONTEPO for additional indications, the development of additional formulations of XENLETA and CONTEPO, plans for making lefamulin available in China, plans to pursue research and development of other product candidates, expectations regarding the ability of customers to satisfy demand for XENLETA with their existing inventory, the sufficiency of Nabriva Therapeutics’ existing cash resources and its expectations regarding anticipated revenues from product sales and how far into the future its existing cash resources will fund its ongoing operations 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: Nabriva Therapeutics’ ability to successfully implement its commercialization plans for XENLETA and whether market demand for XENLETA is consistent with its expectations, Nabriva Therapeutics’ ability to build and maintain a sales force for XENLETA, the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, 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 studies 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 CONTEPO for the treatment of cUTI, the ability to retain and hire key personnel, the availability of adequate additional financing on acceptable terms or at all and such other important factors as are set forth in Nabriva Therapeutics’ annual and quarterly reports and other filings on file with the U.S. Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Nabriva Therapeutics’ views as of the date of this press release. Nabriva Therapeutics anticipates that subsequent events and developments will cause its views to change. However, while Nabriva Therapeutics 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 Therapeutics’ views as of any date subsequent to the date of this press release.