Bedaquiline monotherapy may be effective at improving multibacillary leprosy.

1. In this proof-of-concept study, bedaquiline therapy cleared Mycobacterium leprae by four weeks of treatment in patients with multibacillary leprosy.

2. Bedaquiline monotherapy led to improvement in the appearance of leprosy skin lesions.

Evidence Rating Level: 3 (average)

Study Rundown: Leprosy is a chronic infectious disease that is caused by Mycobacterium leprae. It is characterized by skin lesions or peripheral neuropathy and can be classified as paucibacillary or multibacillary. Multibacillary leprosy is treated with multidrug therapy for 12 months. However, there are many challenges to therapy, including drug resistance and severe side effects. The WHO highlights the need for more effective and shorter drug regimens for the treatment of leprosy. Bedquiline is a diarylquinoline that inhibits the mycobacterial ATP synthase. Preclinical data from mouse models has shown that bedquiline monotherapy has bactericidal activity against M. leprae. This phase two, open-label, proof-of-concept study explored the efficacy and safety of an eight-week regimen of bedaquiline monotherapy in patients with previously untreated multibacillary leprosy. Patients in this study were followed for 112 weeks after they were treated with an eight-week course of bedaquiline followed by standard multidrug therapy. The primary endpoint was the change from baseline in the odds of positive growth of M. leprae in mouse footpads after eight weeks of therapy with bedaquiline. Overall, results from this study found that bedaquiline monotherapy cleared M. leprae by four weeks of treatment in patients with multibacillary leprosy. Bedaqualine monotherapy also led to improvement in the appearance of skin lesions by week 7. Limitations of this study include its small sample size and the conduction in a single country with no comparator group.

Click here to read the study in NEJM

In-Depth [proof of concept study]: This phase two, open-label, proof of concept trial assessed the efficacy and safety of an eight-week regimen of bedaquiline monotherapy in patients with previously untreated multibacillary leprosy. Adult patients up to the age of 65 years with previously untreated multibacillary leprosy classified as either borderline lepromatous or polar lepromatous were eligible for this study. Patients who had received any previous treatment for leprosy received prohibited medications, or had tuberculosis were excluded from this study. A total of nine patients from two sites in Brazil were included in the intention-to-treat analysis. These patients received bedaquiline at an initial dose of 200 mg once daily for two weeks, followed by an oral dose of 100 mg three times per week for six weeks. After this, patients began standard WHO multidrug therapy for leprosy and were followed for 112 weeks. Punch biopsies of skin lesions were performed before treatment and at weeks two, four, and eight. The M. leprae from the biopsies was inoculated into the footpads of mice. The primary endpoint was the change from baseline in the odds of positive growth of M. leprae in mouse footpads after eight weeks of therapy with bedaquiline. The secondary endpoint was safety and exploratory endpoints were clinical signs and symptoms. Assessment of the primary endpoint found that the odds of positive M. leprae growth had decreased from 100% in all patients at baseline to no growth after four weeks of treatment with bedaquiline. All patients showed improvement in the appearance of skin lesions by the seventh week. Seven of the nine patients had experienced at least one adverse event during the treatment duration. Results from this study showed that an eight-week regimen of bedaquiline monotherapy resulted in bactericidal effects in patients with multibacillary leprosy.

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