New Treatment for CABP Continues to Show Positive Outcomes in Clinical Trials
Lefamulin, a pleuromutilin antibiotic, continues to meet primary endpoints for the treatment of community acquired bacterial pneumonia (CABP) in clinical trials.
The leading cause of infectious disease death in the United States is community-acquired bacterial pneumonia (CABP), with more than 5 million adults being treated for the disease each year. The infection is the second highest cause of hospital admissions through the emergency room and because the infection can be severe and potentially life-threatening, many patients end up being readmitted for further treatment. The estimated hospitalization costs to treat the infection are $17 billion. Thus, research and development aimed at a treatment for the infection are booming, and one such company has made an important step forward to bringing a treatment to market.
The clinical-stage biopharmaceutical company, Nabriva Therapeutics, just released positive top-line global Phase 3 trial data on their intravenous (IV) and oral forms of a pleuromutilin antibiotic, lefamulin, for the treatment of community-acquired bacterial pneumonia (CABP) today. The drug met all primary US Food and Drug Administration (FDA) and European Medicines Agency (EMA) endpoints. In this exclusive interview, with Contagion®, Thomas File, MD, MSc, Chair of Infectious Disease Division, Summa Health in Akron, Ohio, explains what pleuromutilin antibiotics are and how they work.
As Dr. File stated, pleuromutilin antibiotics are thought to work against pathogens that have previously thwarted other regimens. This is particularly important for CABP as the Centers for Disease Control and Prevention (CDC) stipulate that, “available data show that pneumococcal bacteria are resistant to one or more antibiotics in 30% of cases.”
The results from the lefamulin clinical trial (LEAP-1) showed that lefamulin met the FDA primary endpoint of non-inferiority (NI, 12.5% margin) compared to moxifloxacin with or without adjunctive linezolid for early clinical response (ECR) assessed 72 to 120 hours following initiation of therapy in the intent to treat (ITT) patient population. In the trial, ECR rates were 87.3% for lefamulin and 90.2% for moxifloxacin with or without linezolid (treatment difference -2.9 [95% confidence interval (CI) -8.5, 2.8]).
Lefamulin also met the primary endpoints for the EMA of non-inferiority (NI, 10% margin) compared to moxifloxacin with or without adjunctive linezolid in the modified intent to treat (mITT) and clinically evaluable at test of cure (CE-TOC) populations based on an investigator assessment of clinical response (IACR) at a test of cure visit (5 to 10 days following the completion of study therapy). IACR rates for the mITT population were 81.7% for lefamulin and 84.2% for moxifloxacin with or without linezolid (treatment difference -2.6 [95% CI -8.9, 3.9]) and for the CE-TOC population were 86.9% for lefamulin and 89.4% for moxifloxacin with or without linezolid (treatment difference -2.5 [95% CI -8.4, 3.4]). IACR is also a key secondary endpoint for the FDA.
When speaking on these top-line results in Nabriva’s official press release, Dr. File is quoted as saying, “CABP is a common and potentially life-threatening illness for which presently available recommended antimicrobials have potential limitations often associated with resistance or safety. With bacterial resistance continuing to increase, patients and physicians are in need of new safe and effective treatment options that adhere to the principles of antibiotic stewardship. These positive topline results evaluating the efficacy and safety of lefamulin in patients with community-acquired bacterial pneumonia are promising.”
These data are from the first of 2 global Phase 3 trials, called LEAP 1. Nabriva expects data from the second pivotal trial—LEAP 2, which is evaluating all oral lefamulin for the treatment of CABP—in the first quarter of 2018. Further analysis of the LEAP 1 trial is ongoing, and additional results will be presented at upcoming scientific congresses.