The Food and Drug Administration has granted an accelerated approval for bedaquiline – the first antituberculosis drug to target the key energy enzyme, adenosine triphosphate.
Because of its novel method of action, bedaquiline fills a previously unmet need, FDA officials said.
"Multidrug-resistant tuberculosis (MDR-TB) poses a serious health threat throughout the world, and [bedaquiline] provides much-needed treatment for patients who have don’t have other therapeutic options available," Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. "Because the drug also carries some significant risks, doctors should make sure they use it appropriately and only in patients who don’t have other treatment options."
Bedaquiline carries a boxed warning about its potential effect on heart rhythm; it has been associated with QT-segment prolongation, which could lead to a potentially fatal dysrhythmia. According to materials submitted to the FDA Anti-Infective Drugs Advisory Committee, 26 patients taking the drug died during the two pivotal phase II studies, compared with four who took placebo. Three deaths were cardiac related, including one from hypertension, one from cardiac arrest associated with pneumonia, one from congestive heart failure, according to the materials submitted by manufacturer Janssen Therapeutics.
The two studies upon which FDA based its approval involved almost 400 patients, all of whom had pulmonary MDR-TB. The first compared a standard, four-drug regimen plus placebo to the same regimen plus 400 mg bedaquiline daily for 2 weeks, followed by 200 mg three times a week for 22 weeks.
At 24 weeks, 78% of those treated with bedaquiline had a culture conversion, compared with 58% of those on placebo, a significant difference. Treatment failure occurred in 23% of the active group and 43% of the placebo group.
The second study was an open-label trial of 233 previously treated patients who still had culture-positive MDR-TB. They received the same dosing regimen of bedaquiline combined with an individualized background regimen. At 24 weeks, sputum conversion was 80%, with negative cultures appearing in a mean of 57 days.
The accelerated approval program allows provisional approval to drugs showing a positive treatment effect for serious disease, based on data from a surrogate endpoint likely to predict clinical benefit – in this case, sputum conversion. Bedaquiline will be available while Janssen conducts confirmatory phase III trials.
Since bedaquiline seems safe and effective for a rare disease without a satisfactory alternative treatment, the FDA also granted it a fast-track designation, priority review, and an orphan drug designation.
The drug will be marketed under the trade name Sirturo.