Xenleta (lefamulin IV) / Nabriva Therap, Sumitomo Pharma, Er-Kim Pharma - LARVOL DELTA

Safety and Pharmacokinetics Following Oral or Intravenous Lefamulin in Adults With Cystic Fibrosis. (PubMed, Clin Ther) - P1 | "These results show similar lefamulin pharmacokinetic and safety profiles between patients with CF and healthy volunteers receiving the same oral and IV doses, suggesting no need for lefamulin dose adjustment in patients with CF and indicating the potential of lefamulin as therapy for lung infections in patients with CF."

Journal • PK/PD data • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Target attainment of intravenous lefamulin for treatment of acute bacterial skin and skin structure infections. (PubMed, J Antimicrob Chemother) - "Lefamulin at the currently approved IV dosage covers most Staphylococcus aureus isolates when targeting drug exposure associated with bacteriostasis, suggesting potential of lefamulin for the treatment of ABSSSIs. Lefamulin may not be appropriate in ABSSSI when rapid bactericidal activity is warranted."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Pharmacokinetic, Pharmacokinetic/Pharmacodynamic, and Safety Investigations of Lefamulin in Healthy Chinese Subjects. (PubMed, Antibiotics (Basel)) - "This study aimed to explore the pharmacokinetics (PK) and safety of oral (PO) and intravenous (IV) lefamulin in healthy Chinese subjects and to evaluate the efficacy of the intravenous administration regimen using pharmacokinetic/pharmacodynamic (PK/PD) analysis. The PK of lefamulin in healthy Chinese subjects were consistent with that in foreign countries. Lefamulin demonstrated the microbiological effectiveness against Streptococcus pneumoniae and Staphylococcus aureus."

Journal • PK/PD data • Infectious Disease • Pneumococcal Infections • Pneumonia

EFFICACY AND SAFETY OF LEFAMULIN IN CHINESE ADULTS WITH COMMUNITY-AQUIRED BACTERIAL PNEUMONIA (CABP): RESULTS OF LEFAMULIN EVALUATION AGAINST PNEUMONIA (LEAP-CHINA) STUDY (CHEST 2023) - " Adults with CABP were randomized 2:1 to receive lefamulin 150 mg IV Q12 hours or moxifloxacin 400 mg IV Q24 hours. This bridging trial met the consistency criteria with LEAP 1, supporting the noninferiority conclusion of lefamulin to moxifloxacin. The frequency of TEAEs was comparable between the two groups. CLINICAL IMPLICATIONS: Lefamulin is a promising new option as empirical monotherapy for Chinese adults with CABP."

Clinical • Infectious Disease • Pneumonia • Respiratory Diseases

Assessing Boron-Pleuromutilin AN11251 for the Development of Antibacterial Agents. (PubMed, Molecules) - "The recent approval of lefamulin for both intravenous and oral doses in humans to treat community-acquired bacterial pneumonia has prompted investigations in modifying the structure to broaden the antibacterial spectrum, enhance the activity, and improve the pharmacokinetic properties. AN11251 has potent activities against the Gram-positive bacterial pathogens tested, including various drug-resistant strains, and against the slow-growing mycobacterial species. Finally, we employed PK/PD modeling to predict the human dose for treatment of disease caused by Wolbachia, Gram-positive bacteria, or Mycobacterium tuberculosis, which might facilitate the further development of AN11251."

Journal • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Study to Assess the Safety and PK of Oral and IV Xenleta in Adults With Cystic Fibrosis (clinicaltrials.gov) - P1 | N=13 | Completed | Sponsor: Nabriva Therapeutics AG | Active, not recruiting ➔ Completed | Trial completion date: Jun 2023 ➔ Jan 2023 | Trial primary completion date: Mar 2023 ➔ Sep 2022

Trial completion • Trial completion date • Trial primary completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Nabriva Therapeutics Announces Positive Topline Results from Phase 1 Trial of XENLETA (lefamulin) in Adult Patients with Cystic Fibrosis (GlobeNewswire) - P1 | N=13 | NCT05225805 | Sponsor: Nabriva Therapeutics AG | "Nabriva Therapeutics plc...announced positive topline results from their Phase 1 clinical trial that assessed the safety and pharmacokinetics (PK) of oral and intravenous (IV) XENLETA® (lefamulin) in adult patients with cystic fibrosis (CF)....'In addition, XENLETA was well-tolerated and the adverse event profile in CF patients was consistent with that described across our clinical program'...look forward to sharing the complete results with the medical community in the first half of 2023.'"

P1 data • PK/PD data • Cystic Fibrosis

Nabriva Therapeutics Pivoting Strategic Focus Reports Third Quarter Financial Results and Provides Corporate Update (GlobeNewswire) - "Three Months Ended September 30, 2022 and 2021: Research and development expenses for the three months ended September 30, 2022 were $4.0 million compared to $3.2 million for the three months ended September 30, 2021. The $0.8 million increase was primarily due to a $0.5 million increase in consulting fees and a $0.4 million increase in research materials and purchased services driven by our Phase 1 trial to assess the safety and pharmacokinetics of oral and intravenous XENLETA for the treatment of resistant bacterial infections in adult patients with cystic fibrosis."

Commercial • Cystic Fibrosis

Nabriva Therapeutics Completes Patient Enrollment in Phase 1 Trial of XENLETA(lefamulin) in Adult Patients with Cystic Fibrosis (GlobeNewswire) - "Nabriva Therapeutics...announced the completion of patient enrollment in its Phase 1 clinical trial to assess the safety and pharmacokinetics of oral and intravenous XENLETA® (lefamulin) in adult patients with cystic fibrosis (CF)...'With enrollment now complete, we expect to report topline data in the first quarter of 2023.'"

Enrollment closed • P1 data • Cystic Fibrosis

Study to Assess the Safety and PK of Oral and IV Xenleta in Adults With Cystic Fibrosis (clinicaltrials.gov) - P1 | N=13 | Active, not recruiting | Sponsor: Nabriva Therapeutics AG | Recruiting ➔ Active, not recruiting

Enrollment closed • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Nabriva Therapeutics Announces First Patient Enrolled in Phase 1 Trial of XENLETA (lefamulin) in Adult Patients with Cystic Fibrosis (GlobeNewswire) - "Nabriva Therapeutics plc...announced that the first patient was enrolled in a Phase 1 clinical trial to assess the safety and pharmacokinetics of oral and intravenous XENLETA® (lefamulin) in adult patients with cystic fibrosis (CF)."

Trial status • Cystic Fibrosis

Nabriva Therapeutics Reports Second Quarter 2022 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Research and development expenses for the six months ended June 30, 2022 were $7.6 million compared to $7.0 million for the six months ended June 30, 2021, which represented an 8% increase. The $0.6 million increase was primarily due to a $0.5 million increase in research materials driven by our Phase 1 cystic fibrosis trial of XENLETA and purchased services, and a $0.1 million increase in travel expenses."

Commercial • Cystic Fibrosis

Lefamulin Efficacy and Safety in Adults with Community-Acquired Bacterial Pneumonia (CABP): Pooled Analysis of the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Trials in Patients with Asthma or Chronic Obstructive Lung Disease (COPD) (ATS 2022) - " In LEAP 1, adults with CABP (PORT risk class III-V; ≥25% required to have PORT risk class IV-V) received IV lefamulin 150mg q12h for 5-7 d or moxifloxacin 400mg q24h for 7 d, with optional IV-to-oral switch. Lefamulin efficacy was high for patients with asthma or COPD and comparable to that with moxifloxacin, and TEAE profiles were similar. Lefamulin is an alternative to fluoroquinolones for treating CABP in patients with comorbid lung disease who have or may be at risk for severe pneumonia."

Retrospective data • Asthma • Cardiovascular • Chronic Obstructive Pulmonary Disease • Congestive Heart Failure • Gastrointestinal Disorder • Heart Failure • Hypertension • Immunology • Infectious Disease • Pneumococcal Infections • Pneumonia • Pulmonary Disease • Respiratory Diseases

Study to Assess the Safety and PK of Oral and IV Xenleta in Adults With Cystic Fibrosis (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Nabriva Therapeutics AG | Not yet recruiting ➔ Recruiting

Enrollment open • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Study to Assess the Safety and PK of Oral and IV Xenleta in Adults With Cystic Fibrosis (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Nabriva Therapeutics AG

New P1 trial • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Nabriva Therapeutics Provides Business Update and Announces Preliminary Financial Results for the Fourth Quarter of 2021 (GlobeNewswire) - 'We have also made significant progress in executing on life-cycle management opportunities for XENLETA with the initiation of a Phase I trial for CF...In 2022, we look for continued growth through execution on key milestones including: Enrolling the first patient in our Phase I CF trial in the first quarter."

Enrollment status • Cystic Fibrosis

Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials. (PubMed, Antibiotics (Basel)) - "In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5-7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens."

Clinical • Journal • P3 data • Infectious Disease • Pneumonia • Respiratory Diseases

Pooled Microbiological Findings and Efficacy Outcomes by Pathogen in Adults With Community-Acquired Bacterial Pneumonia from the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Phase 3 Trials of Lefamulin Versus Moxifloxacin. (PubMed, J Glob Antimicrob Resist) - "Lefamulin is a valuable IV and oral monotherapy option for empiric and directed CABP treatment in adults."

Clinical • Journal • P3 data • Infectious Disease • Pneumococcal Infections • Pneumonia • Respiratory Diseases

NABRIVA THERAPEUTICS PLC MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-Q) (Market Screener) - "We anticipate initiating a Phase 1 clinical trial of XENLETA for the treatment of resistant bacterial infections in patients with cystic fibrosis, or CF, before the end of the first quarter of 2022."

New P1 trial • Cystic Fibrosis

Nabriva Therapeutics to Present Data at IDWeek 2021 (GlobeNewswire) - "Nabriva Therapeutics...announced data presentation at the Infectious Disease Society of America (IDSA) IDWeek™ 2021, taking place virtually from September 29 – October 3, 2021. Nabriva, along with its collaborators, will exhibit a poster presentation on the in vitro activity of lefamulin against Staphylococcus aureus isolated from the lower respiratory tract of children with cystic fibrosis."

Preclinical • Cystic Fibrosis

[VIRTUAL] In vitro activity of lefamulin against bacterial pathogens causing pneumonia and other respiratory tract infections in Europe: results from the SENTRY surveillance programme (2019-2020) (ECCMID 2021) - "Lefamulin IV or IV/oral (5–7 days; 10 days for methicillin-resistant Staphylococcus aureus [MRSA]) and lefamulin oral (5 days) regimens were noninferior to moxifloxacin IV or IV/oral (7 days; 10 days for MRSA) and moxifloxacin oral (7 days) in patients with CAP caused by the most prevalent typical and atypical bacterial pathogens...pneumoniae; whereas amoxicillin/clavulanate and ceftriaxone were active against 83.3% and 86.1% of isolates, respectively...Lefamulin retained potent activity against penicillin-resistant (penicillin MIC >2 mg/L), azithromycin-resistan (azithromycin MIC >0.5 mg/L), and tetracycline-resistant (tetracycline MIC >2 mg/L)... Lefamulin demonstrated potent in vitro activity against contemporary bacteria collected from patients with pneumonia in European medical centres . Lefamulin activity was not adversely affected by resistance to other antimicrobial classes, including β-lactams, macrolides, fluoroquinolones, and tetracyclines . Lefamulin..."

Preclinical • Infectious Disease • Pneumonia • Respiratory Diseases

Nabriva Therapeutics plc (NBRV) CEO Ted Schroeder on Q1 2021 Results - Earnings Call Transcript (SeekingAlpha) - "The expert panel encouraged us to complete a Phase 1 safety and PK study in CF patients. So we're planning to start that study in the second half of this year....We expect to have some non-clinical data in the second half of this year, with clinical data to follow in 2022...We are committed to get through at least the Phase 1 program in cystic fibrosis for XENLETA."

New P1 trial • Preclinical • Cystic Fibrosis

Lefamulin efficacy and safety in a pooled phase 3 clinical trial population with community-acquired bacterial pneumonia and common clinical comorbidities. (PubMed, BMC Pulm Med) - P3 | "Lefamulin may provide a valuable intravenous/oral monotherapy alternative to fluoroquinolones or macrolides for empiric treatment of patients with CABP, including cases of patients at risk for poor outcomes due to age or various comorbidities."

Clinical • Journal • P3 data • Asthma • Atrial Fibrillation • Cardiovascular • Chronic Obstructive Pulmonary Disease • Congestive Heart Failure • Diabetes • Heart Failure • Hypertension • Immunology • Infectious Disease • Metabolic Disorders • Nephrology • Pneumonia • Pulmonary Disease • Renal Disease • Respiratory Diseases

Pharmacokinetics and Safety of Lefamulin After Single Intravenous Dose Administration in Subjects with Impaired Renal Function and those Requiring Hemodialysis. (PubMed, Pharmacotherapy) - "No dosage adjustment is required for patients with renal impairment, and lefamulin can be administered without regard to hemodialysis timing."

Clinical • Journal • PK/PD data • Infectious Disease • Pneumonia • Renal Disease • Respiratory Diseases

Pharmacokinetics and Safety of Lefamulin After Single Intravenous Dose Administration in Subjects with Impaired Hepatic Function. (PubMed, Pharmacotherapy) - "Lefamulin was generally well tolerated. Differences in lefamulin and BC-8041 pharmacokinetics were small, relative to the overall variability, and any changes appear to be compensated by increases in renal clearance and decreased protein binding."

Clinical • Journal • PK/PD data • Infectious Disease • Pneumonia • Respiratory Diseases