Yesterday, Nov. 28th, the FDA Ant-infective Drug Advisory Committee voted to recommend Janssen‘s Bedaquiline for accelerated approval for the treatment of MDR tuberculosis. You can access materials from the meeting at http://www.fda.gov/AdvisoryCommittees/Calendar/ucm321011.htm. The sponsor and scientists from the FDA both made presentations. Also, members of the public were allowed to speak including Mel Spigelman (TB Alliance, WGND), Christian Lienhardt (WHO, WGND), and Mark Harrington (TAG). During the questioning and discussion the following questions and concerns were brought up:

• Lower exposure of drug in Blacks compared to other races, there were similar treatment success between groups but there was thought that more data was needed to insure this was not an issue
• There was limited data in HIV+ patients.
• There was discussion of the predictive value of surrogate endpoint of sputum conversion and most felt it was sufficient for accelerated approval but not for when Janssen seeks traditional approval.
• How to consider the fact that there were about 100 cases of MDR in the US and the decision to approve Bedaquiline would have global implications.
• Data showing mortality imbalance resulted in a significant amount of discussion because the role of Bedaquiline could not be ruled out in most cases but there was no correlation between the deaths and the drug.

The Committee was asked to consider and vote on two questions with the following results:

1. Do the data provided by the applicant provide substantial evidence of the efficacy of bedaquiline for the proposed indication of treatment of pulmonary tuberculosis due to MDR M. tuberculosis as part of combination therapy in adults (≥ 18 years)? (Vote)

a. If not, what additional data are required?

b. If so, is the surrogate endpoint of sputum conversion sufficient for traditional approval? [rephrased]

c. If so, please discuss any recommendations for labeling and use of bedaquiline.

VOTE: 18 yes/0 no

2. Do the data provided by the applicant provide substantial evidence of the safety of bedaquiline for the proposed indication of treatment of pulmonary tuberculosis due to MDR M. tuberculosis as part of combination therapy in adults (≥ 18 years)? (Vote)

a. If not, what additional data are required?

b. If so, please discuss any recommendations for labeling and risk management.

VOTE: 11 yes/7 no

The FDA will consider the Advisory Committee’s recommendation and make a final decision on the accelerated approval of Bedaquiline by Dec. 29th.