FDA Approves Pediatric Formulation of Bedaquiline for Multidrug-Resistant TB


The FDA has approved bedaquiline for use in combination therapy for the treatment of patients 5 years and older with pulmonary multi-drug resistant tuberculosis.

Johnson & Johnson has announced that the US Food and Drug Administration (FDA) has approved bedaquiline for use in combination therapy for the treatment of patients 5 years and older with pulmonary multi-drug resistant tuberculosis (TB). Further research is underway in younger patients.

Bedaquiline is a diarylquinoline antimycobacterial drug. The drug can be administered with a 20-milligram tablet taken conventionally or mixed into water for pediatric patients who have difficulty swallowing an intact tablet.

The formulation was granted accelerated approval by the FDA, based on time to sputum culture conversion, but continuing approval will depend on observations of clinical benefit in confirmatory trials.

The FDA approval was also supported by evidence from a single-arm, open-label, Phase 2 study which enrolled pediatric patients between the ages of 5-12 years with confirmed or likely pulmonary multi-drug resistant TB. Patients were treated with half of the adult dose with 20 mg tablets for 24 weeks alongside a background regimen for treatment.

Bedaquiline first received approval in 2012, for adult patients. In 2019, bedaquiline was approved for adolescents between ages 12-17 years.

In its press release, Johnson and Johnson outlined exceptions in which the drug should not be used. Circumstances include when another effective treatment regimen can be provided, in cases of latent TB, drug-sensitive or extra-pulmonary TB, or in treating infections caused by other mycobacteria. Data concerning safety and efficacy in treatment of patients living with HIV are limited, the company noted. In clinical trials, hepatic-related adverse reactions were reported in adults.

Adverse events relative to placebo included nausea (38% vs 32%), arthralgia (33% vs 22%), headache (28% vs 12%), hemoptysis (18% vs 11%), chest pain (11% vs 7%), anorexia (9% vs 4%), transaminases increased (9% vs 1%), rash (8% vs 4%), and blood amylase increased (3% vs 1%).

Pregnancy studies performed in animal models revealed no evidence of harm to the fetus due to oral administration of bedaquiline, but evidence in human patients is limited.

Other safety details highlighted by the company included findings in which an increased risk of death was seen in a treatment group (11.4%) compared to the placebo group (2.5%) in a placebo controlled trial in adults. QT prolongation is also known to occur, particularly when the drug is used alongside other drugs with similar cardiac risks. This means bedaquiline is intended for use as a last resort when other regimens are not considered viable.

“If necessary, bedaquiline treatment initiation could be considered in these patients after a favorable benefit risk assessment and with frequent ECG monitoring,” authors of the press release noted.

Tuberculosis is one of the world’s most serious perpetual disease burdens, impacting a great number of adults and children alike. In 2018, 10 million people fell ill with tuberculosis and 1.5 million people died. In 2019, the World Health Organization estimated that there were 205,000 deaths due to TB in children younger than 15.

“TB is already an often-overlooked area in global health, and children with the disease are especially vulnerable. Modernizing pediatric treatment is a critical step toward reducing the suffering of these young patients and ending TB once and for all,” said Martin Fitchet, MD, Head for Global Public Health at Johnson & Johnson, in the company’s announcement.

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