NBRV Nabriva Therapeutics PLC

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 the Journal of the American Medical Association (JAMA) has published results from the company’s Lefamulin Evaluation Against Pneumonia 2 (LEAP 2) clinical trial. The U.S. Food and Drug Administration (FDA) approved lefamulin on August 19, 2019 under the brand name XENLETA™, which is now available for the treatment of adults with CABP.  XENLETA is the first IV and oral antibiotic with a novel mechanism of action approved by the FDA in nearly two decades.

In the study, the second of two global, pivotal Phase 3 clinical trials of lefamulin, clinicians evaluated the safety and efficacy of five days of oral lefamulin compared to seven days of oral moxifloxacin, a respiratory fluoroquinolone, in adult patients with moderate CABP (PORT risk class II, III, or IV). In this study, a short course (5-days) of lefamulin was shown to be noninferior to a 7-day regimen of moxifloxacin for the treatment of CABP. Lefamulin achieved high clinical response rates for both typical (Streptococcus pneumoniae - including multi-drug resistant strains, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus), as well as atypical pathogens (Mycoplasma pneumoniae, including macrolide-resistant strains, Chlamydophila pneumoniae, and Legionella pneumophila). Both lefamulin and moxifloxacin were generally well tolerated with low and similar incidence of discontinuations due to adverse events.  

“The increasing prevalence of antimicrobial resistance in the most common causative pathogens of CABP, along with growing evidence of safety concerns with fluoroquinolones makes a compelling case for the development of new antibacterial classes with novel mechanisms of action (MOA) to treat patients with CABP,” said Jennifer Schranz, MD, Chief Medical Officer of Nabriva Therapeutics. “Xenleta is the first novel MOA antibiotic approved in the United States in nearly 20 years. The results from the LEAP clinical trial program, combined with lefamulin’s targeted spectrum of activity, which aligns with the principles of antimicrobial stewardship, make it an attractive short-course, monotherapy treatment option for adults with CABP.”

The publication, entitled “Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults with Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial,” is available online.

In a related editorial published in the same edition, entitled “Lefamulin – A New antibiotic for Community-Acquired Pneumonia,” author Preeti N. Malani, MD, MSJ, Division of Infectious Diseases at the University of Michigan and Associate Editor of JAMA, states “…lefamulin is an important addition to the current antibiotic armamentarium, especially because bacterial pneumonia remains one of the most common indications for antibiotic use.”

LEAP 2 Study

The Phase 3, double-blind, double-dummy, parallel-group, noninferiority randomized trial was conducted in 99 sites in 19 countries. The clinical trial randomized 738 patients 18 years of age or older who had had Pneumonia Outcomes Research Team (PORT) risk class II, III, or IV, radiographically documented pneumonia, acute illness, greater than three CABP symptoms, and greater than two vital sign abnormalities. Randomization was stratified by PORT risk class (II vs III/IV), geographic region (US vs ex-US), and prior receipt of a single dose of short-acting antibiotic therapy for CABP (yes vs no). Per protocol, ≤25 percent of the study population could have received a single dose of a short-acting antibiotic, and ≥50 percent were to have PORT risk class of III or IV. The first patient visit was on August 30, 2016, and patients were followed for 30 days, with the final date of follow-up on January 2, 2018.

Patients were randomized 1:1 to receive oral lefamulin (600 mg every 12 hours for 5 days; n = 370) or moxifloxacin (400 mg every 24 hours for 7 days; n = 368).

The primary endpoint for the study was early clinical response (ECR) at 96±24 hours after the first dose of either study drug in the intent-to-treat (ITT) population (all randomized patients). Responders were defined as alive, showing improvement in greater than two or more of the four CABP symptoms, having no worsening of any CABP symptoms, and not receiving any non-study antibacterial drug for current CABP episode. The European Medicines Agency coprimary endpoints (FDA secondary endpoints) were investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10 days after last dose) in the modified ITT (mITT; randomized and received any amount of study drug) population and in the clinically evaluable (CE; met pre-defined inclusion/exclusion criteria, minimal dosing requirements) population. The noninferiority margin was 10 percent for ECR and IACR.

Study results showed that ECR rates were 90.8 percent with lefamulin and 90.8 percent with moxifloxacin, meeting the noninferiority margin of 10 percent. IACR rates were 87.5 percent with lefamulin and 89.1 percent with moxifloxacin in the modified ITT population and 89.7 percent and 93.6 percent, respectively, in the clinically evaluable population at test of cure. Lefamulin was well tolerated during the trial. The most frequently reported treatment-emergent adverse events for lefamulin were diarrhea, nausea and vomiting, predominantly mild to moderate, manageable and which rarely led to discontinuation.

“The results from this randomized clinical trial will inform more clinicians of lefamulin’s potential as an effective alternative to commonly used antibiotics, such as fluoroquinolones or macrolides, to fight community acquired pneumonia, which affects five million Americans each year,” said Gregory Moran, MD., Chief, Olive View-UCLA Medical Center.

About XENLETA

XENLETA (lefamulin) is a first-in-class semi-synthetic pleuromutilin antibiotic for systemic administration in humans discovered and developed by the Nabriva Therapeutics team. It is indicated for the treatment of adults with CABP caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae. It is designed to inhibit the synthesis of bacterial protein, which is required for bacteria to grow. XENLETA’s binding occurs with high affinity and high specificity at molecular sites that are different than other antibiotic classes, resulting in a lower risk of developing resistance and cross-resistance to other commonly used antibiotics.

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) 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 www.nabriva.com.

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION

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.

USAGE

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

CONTRAINDICATIONS

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.

ADVERSE REACTIONS

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.

Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for Nabriva Therapeutics, including but not limited to statements about launch and commercialization of XENLETA for the treatment of CABP, 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 XENLETA and 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 to pursue research and development of other product candidates, the sufficiency of Nabriva Therapeutics’ existing cash resources 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 and prepare for commercial launch of XENLETA on the timeline expected, or at all, 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 or of XENLETA for the treatment of CABP, the ability to retain and hire key personnel, the sufficiency of cash resources and need for additional financing 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.

CONTACTS:

For Investors Gary Sender Nabriva Therapeutics plc ir@nabriva.com 

For Media Mike Beyer Sam Brown Inc. mikebeyer@sambrown.com 312-961-2502