New tuberculosis drug bedaquiline approved by U.S. Food and Drug Administration
On 28 December 2012, the U.S. Food and Drug Administration approved bedaquiline, a new diarylquinoline antimycobacterial drug, as part of combination therapy to treat adults with multi-drug resistant tuberculosis (MDR-TB) when other alternatives are not available.
On 28 December 2012, the U.S. Food and Drug Administration approved bedaquiline, a new diarylquinoline antimycobacterial drug, as part of combination therapy to treat adults with multi-drug resistant tuberculosis (MDR-TB) when other alternatives are not available.
The drug has been approved on the basis of the results of two phase II trials including 440 newly diagnosed MDR-TB patients in total. Patients in the first trial were randomly assigned to be treated with bedaquiline or placebo in combination with a standard five-drug, second-line anti-tuberculosis regimen for 8 weeks (1). In the second trial all patients received bedaquiline for 24 weeks in addition to other TB drugs. Both studies were designed to measure the time to conversion to a negative sputum culture. Results from the first trial showed that patients treated with bedaquiline and a combination of other drugs achieved culture conversion in a median time of 78 days, compared with 129 days in patients treated with placebo and a combination of other drugs (2). Results from the second trial showed a median time to culture conversion of 57 days, supporting the efficacy findings of the first trial (3).
The currently available safety data are from the above mentioned phase II trials and therefore limited. The main safety issues encountered were prolongation of the QT interval not related to clinically significant dysrhythmia; unexplained increased mortality in the patient group treated with bedaquiline; hepatic-related adverse drug reactions; and interactions with CYP3A4 inducing/inhibiting drugs (4).
Bedaquiline should be used in combination with at least 3 other drugs to which the patient’s MDR-TB isolate has been shown to be susceptible in vitro.
MDR-TB in the European Union
Of the 73,996 tuberculosis (TB) cases notified in the EU/EEA in 2010, 1,447 were known to be resistant to rifampicin and isoniazid and were thus classified as multi-drug resistant TB (MDR-TB). Of the total number of MDR-TB patients notified in 2008, only 30% were successfully treated. The availability of a new drug for treatment of MDR-TB can help in reaching better treatment results.
The World Health Organization is initiating a review process aimed at developing rapid interim guidance on the potential use of bedaquiline for the treatment of MDR-TB. An expert review meeting will be convened for this purpose at the end of January 2013.
In the European Union, the European Medicines Agency is evaluating this new drug. Another novel compound for treatment of MDR-TB, Delamanid, has also been filed to the Agency for approval and results are expected in early 2013.