New Medicines

XenletaModerate to severe community-acquired pneumonia


New molecular entity
Nabriva Therapeutics
Nabriva Therapeutics

Development and Regulatory status

Licensed but not launched
Licensed but not launched
Jul 22Nabriva Therapeutics enter into an exclusive distribution agreement with Er-Kim for distrubution rights for oral and i.v. formulations of lefamulin. Er-Kim gains rights to distribute lefamulin in Bulgaria, Croatia, Czechia, Greece, Hungary, Poland, Romania, Slovakia, and Slovenia. Er-Kim may also may distribute lefamulin to an additional 5 countries through a Named Patient Usage (NPU) program. [20]
Jan 22Nabriva indicates plans for geographic expansion of commercialisation and distribution partnerships for lefamulin in the EU and the rest of the world in 2022. [19]
May 21Company presentation indicates that they plan to progress discussions with potential European and other territory partners for XENLETA.[18]
Jul 20The EC has approved the marketing authorization application for lefamulin for the treatment of community-acquired pneumonia (CAP) in adults [16].
May 20Recommended for EU approval by CHMP - the full indication is "for the treatment of community-acquired pneumonia (CAP) in adults when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of CAP or when these have failed." [15]
Jan 20Under evaluation in EU. [14]
Sep 19Launched in US. [13]
Aug 19FDA approves Xenleta (lefamulin) to treat adults with community-acquired bacterial pneumonia [11].
May 19MAA has been submitted to the European Medicines Agency (EMA) for oral and IV lefamulin to treat community-acquired pneumonia (CAP) in adults 18 years of age and older [9].
Aug 18Application submitted to FDA for oral and intravenous (IV) formulations of lefamulin to treat community acquired pneumonia [9].
May 18Nabriva announce plans to submit a marketing application to the US FDA in Q4 of 2018 and an MAA with the EMA a few months later [8].
Feb 18Company pipeline lists lefamulin for CABP as being in PIII trials. Data from the LEAP 2 trial expected in spring 2018 [7].


Pleuromutilin antibiotic, interferes with bacterial protein synthesis via a specific interaction with the 23S rRNA of the 50S bacterial ribosome subunit
The annual incidence of CAP is ~1% of the UK adult population (~524,000 people); between 20-40% of these will be admitted to hospital (~100,000 to 200,000 adults). Around 10% of those admitted might be eligible to receive this after 1st-line antibiotic choices have not worked.
Moderate to severe community-acquired pneumonia

Trial or other data

Mar 21Post-hoc evaluation of LEAP 2 study (n=736) found similar clinical success rates for oral lefamulin vs oral moxifloxacin for patients with Pneumonia Outcomes Research Team risk classes II‒IV (89-91% vs 88-91%) and CURB-65 score 2‒3 (87‒90% vs. 82‒88%) [17].
Oct 19LEAP 2 RCT (n=738) is published; it found that among patients with community-acquired bacterial pneumonia (CABP), 5-day oral lefamulin was non-inferior to 7-day oral moxifloxacin with respect to early clinical response at 96 hours after first dose; 90.8% vs. 90.8% respectively [12].
May 19Positive topline results from PIII clinical trial (LEAP 2, NCT02813694) of oral lefamulin vs. oral moxifloxacin in adults with moderate CABP which compared the safety and efficacy of 5 days of oral lefamulin to 7 days of oral moxifloxacin. The primary endpoint was non-inferiority vs. moxifloxacin for early clinical response (ECR) 72 to 120 hours after therapy started. The ECR was 90.8% for the 5 day treatment of lefamulin and 90.8% for the 7 day treatment course of moxifloxacin. The antibiotic also met the European Medicines Agency (EMA)’s primary endpoint of non-inferiority compared to moxifloxacin.[8]
Feb 18Company pipeline states that LEAP 2 topline data expected in spring 2018.[7]
Sep 17Positive topline results from the LEAP study [NCT02559310] announced. Lefamulin (IV then oral) was non-inferior to moxifloxacin +/- adjunctive linezolid (IV then oral) for early clinical response (ECR) assessed 72 to 120 hours after starting therapy (US FDA NI margin; 12.5% and EMA NI margin; 10%). ECR rates were 87.3% and 90.2% for the lefamulin (n=276) and moxifloxacin +/- linezolid (n=275) groups respectively (treatment difference -2.9 [95% CI -8.5, 2.8]). Adverse effects were reported by around 38% of patients across both groups. Rates of study drug discontinuation were 2.9% for lefamulin versus 4.4% for moxifloxacin +/- linezolid and death occurred with similar frequency in both arms. Adverse events were hypokalemia (2.9% vs. 2.2%), nausea (2.9% vs. 2.2%), insomnia (2.9% vs. 1.8%), infusion site pain (2.9% vs. 0%), infusion site phlebitis (2.2% vs. 1.1%), ALT increase (1.8% vs. 2.2%), hypertension (0.7% vs. 2.2%) and diarrhoea (0.7% vs. 7.7%) for the lefamulin and moxifloxacin +/- linezolid groups respectively. Changes in QT interval were reported with similar frequency between groups affecting around 4-5% of those studied [5,6].
Dec 16Nabriva announce that the LEAP trial (NCT02559310) has achieved 60% recruitment, allowing a pre-specified blinded interim analysis to be carried out - this is intended to confirm sample size and power calculations. The independent data monitoring committee is expected to issue recommendations in February 2017: if original sample size is confirmed, enrolment of the estimated 550 patients is expected to be complete by the end of Q2 2017 [4].
Jun 16the second planned PIII study, the LEAP-2 trial (NCT02813694), is intended to compare oral lefamulin with oral moxifloxacin in patients with moderate CAP. Primary outcome is reported symptom improvement at 4 days from first dose, estimated enrolment is 738, and estimated primary outcome completion date is August 2017 [3].
Jan 16NCT02559310 (LEAP) (EudraCT Number: 2014-005169-63) a PIII RCT comparing the efficacy and safety of lefamulin (BC 3781) vs moxifloxacin (with or without adjunctive linezolid) in 550 adults with community-acquired bacterial pneumonia. The study started in Sep 15 and is due to complete Aug 17 [1]. This is the first of two planned PIII studies for moderate to severe CAP [2]

Evidence based evaluations