FDA Committee Supports Accelerated Approval of TB Drug Bedaquiline

The U.S. Food and Drug Administration (FDA) Anti-Infective Drugs Advisory Committee this week gave a favorable opinion on Janssen's request for accelerated approval of its investigational tuberculosis drug bedaquiline (also known as Sirturo, formerly TMC207) for treatment of multidrug-resistance TB (MDR-TB). alt

The FDA panel unanimously supported the drug's efficacy in treating MDR-TB, a growing global problem for which there are few existing good therapies. Bedaquiline works by a novel mechanism -- interfering with mycobacterial energy production -- so it remains active against bacteria that have developed resistance to existing drug classes. In Phase 2 clinical trials, bedaquiline used as part of a combination regimen with existing drugs accelerated clearance of TB bacteria.

Adverse events occurred more often among patients receiving bedaquiline in Phase 2 clinical trials, but these were largely due to tuberculosis itself, and committee members had mixed opinions about whether the study drug might have been a contributing factor. They noted that more data is needed about whether bedaquiline causes liver or heart toxicity, as some patients developed prolonged QT intervals (an abnormal heart rhythm).

A Phase 3 trial is planned for 2013 to gather further information about bedaquiline's safety and effectiveness. More data is also needed on use of the new drug in people with HIV, who account for a large proportion of TB patients worldwide.

Janssen has proposed making bedaquiline available only through public health agencies in the U.S., limiting its use to people with drug-resistant TB. Bedaquiline has the potential for wider use in other countries where MDR-TB is more prevalent. The FDA is not required to follow its advisory committees' recommendations, but it typically does so.

The Treatment Action Group (TAG), which started as an HIV/AIDS treatment advocacy organization, welcomed the FDA review of bedaquiline, noting that only half of MDR-TB patients are cured with existing treatment options and 15% of people with MDR-TB die while undergoing treatment.
"TAG urges the FDA to consider bedaquiline’s potential to make MDR-TB treatment more effective, shorter, easier, and safer -- particularly in the context of the exorbitant cost and inadequacy of existing treatment options," the group wrote. "TAG’s hope is that this submission of bedaquiline for MDR-TB will herald a renaissance in TB drug development."

Below is an edited excerpt from a press release issued by Janssen Research & Development describing the committee's decision and supporting research.

FDA Advisory Committee Recommends Accelerated Approval of Investigational Multi-Drug Resistant Tuberculosis Treatment Bedaquiline

Raritan, NJ -- November 28, 2012 -- Janssen Research & Development, LLC (Janssen) today announced that the Anti-Infective Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA), in a unanimous vote (18-0), agreed that the efficacy findings for investigational bedaquiline support the proposed indication for the treatment of pulmonary multi-drug resistant tuberculosis (MDR-TB) as part of combination therapy in adults. The committee agreed in a vote of 11-7 that the safety findings supported the proposed indication.

"We are pleased with the committee’s recommendation and look forward to working with the FDA to bring this important therapy to patients who suffer from MDR-TB," said Wim Parys, Global Head of Development, Infectious Diseases and Vaccines, Janssen. "The positive recommendation from the FDA advisory committee is an important step toward achieving that goal."

The FDA assigned a Priority Review designation to the New Drug Application (NDA) filed by Janssen in June seeking accelerated approval for bedaquiline. Recommendations and findings from the advisory committee will be considered by the FDA in its review of the NDA for bedaquiline, but the FDA is not bound to follow them.

About the clinical development program

The regulatory submission is supported by 24-week data from the Phase 2 clinical development program.

Bedaquiline was evaluated in two Phase 2 studies in patients with MDR-TB. TMC207-C208 was designed with two independent stages. Stage 1 was a controlled, randomized, exploratory trial in which 47 patients were treated for eight weeks with either bedaquiline or placebo in combination with a standardized background regimen for MDR-TB. In Stage 2, a controlled and randomized superiority trial, 160 patients were treated with either bedaquiline (400 mg once daily for two weeks followed by 200 mg three times a week for 22 weeks) or placebo in combination with a standardized background regimen for MDR-TB. Background therapy was continued for an additional 12 to 18 months. The primary endpoint was time to culture conversion.

A second single-arm, open-label, Phase 2 study, TMC207-C209, enrolled 233 patients from 11 countries to evaluate the efficacy, safety and tolerability of bedaquiline in the treatment of MDR-TB. Bedaquiline was dosed 400 mg once daily for two weeks followed by 200 mg three times weekly for 22 weeks in combination with an individualized background regimen for MDR-TB, followed by continued administration of the background regimen for 12 to 18 months.

A confirmatory Phase 3 trial, TMC207-C210, is planned for 2013. It is designed as a double-blind study comparing nine months of treatment with bedaquiline versus placebo (both with a background regimen).

About Janssen Research & Development, LLC

Janssen Research & Development, LLC is headquartered in Raritan, NJ and has affiliated facilities in Europe, the United States and Asia. Janssen Research & Development is leveraging a combination of internal and external innovation to discover and develop novel medicines and solutions in five distinct therapeutic areas: Neuroscience, Oncology, Immunology, Infectious Diseases and Vaccines, and Cardiovascular and Metabolism. For more information about Janssen Research & Development, LLC visit Janssen Research & Development is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Driven by our commitment to patients, we work together to bring innovative ideas, products, services and solutions to address serious unmet medical needs around the world.



Janssen Research & Development. FDA Advisory Committee Recommends Accelerated Approval of Investigational Multi-Drug Resistant Tuberculosis Treatment Bedaquiline. Press release. November 28, 2012.

Treatment Action Group Welcomes FDA Review of First New Tuberculosis Drug in Half a Century. Press release. November 29, 2012.