Nabriva Therapeutics Announces Positive Topline Results from Pivotal Phase 3 Clinical Trial of Oral Lefamulin for the Treatment of Community-Acquired Bacterial Pneumonia
- Lefamulin met all
and was shown to be generally well tolerated -
- Company plans to file a New Drug Application with the
in the fourth quarter of 2018 -
- Conference call and webcast today at
In LEAP 2, lefamulin met the
“Today marks an exciting advance in the treatment of CABP as we are one step closer to potentially making a much-needed new class of antibiotics available to patients and health care providers,” said Dr.
Lefamulin also met the
“Coupled with our successful LEAP 1 trial, the positive results from LEAP 2 suggest lefamulin could be an excellent empiric treatment option for patients with CABP and help address the problem of antibiotic resistance. With these LEAP 2 results, we believe there is a significant opportunity for oral lefamulin as a 5-day treatment option for CABP in the community,” said Dr.
“Pneumonia is the leading cause of infection-related deaths and the second leading cause of total hospitalizations in the United States,” said
Additional Clinical Trial Information
LEAP 2 was a global, randomized, double-blind, double-dummy trial that compared the efficacy and safety of 600 mg of oral lefamulin twice a day for 5 days versus 400 mg of oral moxifloxacin once daily for 7 days in 738 patients (370 in the lefamulin arm and 368 in the moxifloxacin arm). The lefamulin arm enrolled 183 (49.5%), 145 (39.2%) and 40 (10.8%) patients with a Pneumonia Outcomes Research Team (PORT) class of 2, 3 and 4, respectively. The moxifloxacin arm enrolled 189 (51.4%), 133 (36.1%) and 42 (11.4%) patients with a PORT class of 2, 3 and 4, respectively. Almost all patients completed the study (95.8%) through late follow-up, which occurred 30 days after administration of the first dose of study medication.
In this trial, lefamulin was generally well tolerated. The rate of treatment-emergent adverse events (TEAEs) was 32.6% in the lefamulin arm and 25.0% in the moxifloxacin arm. Serious treatment emergent adverse events occurred in 4.6% of lefamulin-treated patients and 4.9% of moxifloxacin-treated patients. One related serious adverse event occurred in a moxifloxacin-treated patient (0.3%). Death within 30 days occurred in three patients in each treatment arm (0.8%).
A low percentage of patients discontinued study drug in the lefamulin arm (6.8%) and in the moxifloxacin arm (7.6%). TEAEs leading to discontinuation of study drug were uncommon and were observed in 3.0% of patients in the lefamulin arm and 2.2% of patients in the moxifloxacin arm.
Adverse events reported in greater than 1.0% of patients receiving study drug (lefamulin versus moxifloxacin) were diarrhea/loose stools (12.2% versus 1.1%), nausea (5.2% versus 1.9%), vomiting (3.3% versus 0.8%), hypertension (1.4% for both), respiratory tract infection viral (1.4% vs. 0.3%), headache (1.1% vs. 1.6%), gastritis (1.1% vs. 0.5%), pneumonia (1.1% vs. 0.3%), COPD (1.1% vs. 0%), urinary tract infection (0.8% vs. 1.6%), increased ALT (0.8% vs. 1.1%), increased AST (0.5% vs. 1.1%), anemia (0% vs. 1.1%), and insomnia (0% vs. 1.1%). All cases of diarrhea/loose stools in the lefamulin arm were mild (71.1%) or moderate (28.9%) and were generally of short duration (approximately 2 days). No cases were severe, and none led to discontinuation of study drug. One patient who had a positive clinical response to lefamulin was later diagnosed with a C. difficile infection during an extended hospital stay.
In addition, hepatobiliary TEAEs occurred in 1.1% and 0.5% of subjects receiving lefamulin and moxifloxacin, respectively. There was a low incidence of liver enzyme elevation in both treatment groups consistent with the CABP patient population. Cardiac TEAEs were reported in 2.2% and 2.4% of patients receiving lefamulin and moxifloxacin, respectively. Changes in QT interval of potential clinical concern were rare and of similar frequency between treatment groups.
Further analysis of the LEAP 2 trial results including analysis of additional patient population groups in the trial and secondary and exploratory endpoints related to these population groups is ongoing and additional results will be presented at upcoming scientific congresses.
Conference Call and Webcast
The Company will host a conference call and webcast at
About LEAP 2 Study Design
LEAP 2 was a multi-center, randomized, controlled, double-blind, global study designed to evaluate the efficacy and safety of oral lefamulin compared to oral moxifloxacin, a fluoroquinolone antibiotic, in 738 adults with moderate CABP. Lefamulin was dosed orally at 600 mg every 12 hours for 5 days. Moxifloxacin was dosed according to the approved labeling, 400 mg orally once daily for 7 days. All patients to be enrolled in this trial were to have a Pneumonia Outcomes Research Team (PORT) risk class severity of 2, 3, or 4 on a scale of 1 to 5, which corresponds to moderate clinical disease. Randomization was 1:1 and was stratified by PORT risk class, geographic region, and exposure to prior antibiotics. No more than 25% of patients were allowed to have received a single dose of a short acting oral or IV antibacterial for the treatment of CABP and patients who received more than a single dose within 72 hours before randomization were excluded from participating.
For LEAP 2, the primary efficacy endpoint for the
Based on Nabriva Therapeutics’ combined analysis of the U.S. Centers for Disease Control and Prevention’s 2007 National Ambulatory Medical Care Survey, the National Hospital Ambulatory Medical Care Survey and 2013 data from the Healthcare Cost and Utilization Project,
Any statements in this press release about future expectations, plans and prospects for
Source: Nabriva Therapeutics US, Inc