International AIDS Society

FDA Panel Advises Approval of First Novel Anti-TB Drug in 40 Years

Author: Mark Mascolini

04 December 2012

A panel of the US Food and Drug Administration (FDA) recommended approval of bedaquiline, an antituberculosis drug with a novel mechanism of action that could make it valuable in treating multidrug-resistant TB, Reuters reports. Bedaquiline would be the first drug in 40 years with a new mechanism of action against tuberculosis.

But phase 2 trials completed so far raise questions about the liver and heart safety of bedaquiline, according to Reuters. People taking bedaquiline had elevated liver enzymes, a signal of liver disease, and increases in the QT interval on electrocardiograms, which could point to an electrical irregularity in the heart.

In one of the trials, 10 of 79 people taking bedaquiline and standard anti-TB drugs died, compared with 2 of 81 people taking only standard drugs. However, 21% fewer people taking the bedaquiline-containing regimen than a standard regimen had signs of Mycobacterium tuberculosis in sputum.

The FDA panel agreed in a vote of 18 to 0 that the two phase 2 trials completed so far provide “substantial evidence” of the efficacy and safety of bedaquiline in adults. The panel voted 11 to 7 when considering bedaquiline’s overall safety.

Janssen, the developer of bedaquiline, hopes the FDA will agree with the advisory panel and grant the novel drug accelerated approval. Janssen plans a larger phase 3 trial to assess the efficacy and safety of bedaquiline.

The two phase 2 trials tested two doses of bedaquiline plus standard anti-TB drugs for 24 weeks, followed by standard treatment alone for 12 to 18 months. The phase 3 trial would compare bedaquiline plus standard drugs with standard drugs alone for 9 months, a period much shorter than the 18 to 24 months usually recommended to treat multidrug-resistant TB.

Tuberculosis is the leading cause of death in HIV-positive people in many parts of sub-Saharan Africa. The World Health Organization recorded 310,000 cases of multidrug-resistant TB in 2011, 60% of them in India, China, and Russia.

Source: Ransdell Pierson. FDA advisory panel backs J&J tuberculosis drug. Reuters. 29 November 2012.

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