TB Notes Newsletter
No. 1, 2013
On December 31, 2012, the Food and Drug Administration (FDA) announced the approval of bedaquiline (BDQ) for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pulmonary TB. The manufacturer, Janssen, expects BDQ to be commercially available in the second quarter of this year. Bedaquiline is a diarylquinoline antimycobacterial drug that inhibits an enzyme necessary for energy production by Mycobacterium tuberculosis.
On January 15-16, 2013, CDC convened a multi-agency expert consultancy on BDQ. Participants included 27 external consultants consisting of representatives from state and local TB control offices, the FDA, the Treatment Action Group (TAG), and other national TB experts. In addition, there were Center-level participants and several invited speakers from DTBE. CDC gathered these experts and stakeholders to hear the evidence-based data on the new TB drug BDQ for pulmonary MDR TB; to determine whether efficacy and safety have been shown; and if so, to provide recommendations that will inform CDC guidelines for rollout and monitoring of use of the drug in the United States.
Following introductions and review of administrative matters, the group was given its charge. Questions to the consultancy were reviewed and discussed. The questions were as follows:
- In regard to its efficacy and safety, should BDQ be used for the treatment of MDR/XDR TB in the United States ?
- If so, what are the indications for its use and what criteria will determine who is a candidate (inclusion and exclusion criteria); in what subpopulations should the drug not be used (may be the basis for an Investigational New Drug application [IND])?
- How long should patients be treated with BDQ (may be the basis for an IND)?
- How do we test M. tuberculosis for drug resistance to BDQ?
- Agar? MGIT? Molecular results?
- What labs should be involved with testing?
- What type of monitoring (for adverse events and response) should be performed for patients being treated with BDQ and at what intervals?
- What platform should be used for tracking and monitoring patient outcomes/other variables?
- Web-based system (probably the best way)
- Include patient identifiers?
- Who owns the data?
- Can the company host programs and then transfer data to CDC?
- What multidrug regimens should include BDQ?
The group heard presentations from two FDA experts. Ariel Porcalla, MD, MPH, presented an overview of the efficacy and safety of BDQ based on clinical trials data. Dakshina M. Chilukuri, PhD, provided information on the clinical pharmacology and pharmacokinetics of BDQ. These talks were followed by questions from participants.
A working lunch included a moderated discussion of the efficacy and safety of BDQ.
Topics for the afternoon sessions included the following:
- Global epidemiology of MDR/XDR TB
- Epidemiology of MDR/XDR TB in the United States
- Challenges in the treatment and management of MDR/XDR TB: The experience of the CA MDR TB consultation service
- Molecular Detection of Drug Resistance (MDDR) service update
- Discussion of specific questions to the expert consultant group
At 5:00 pm the group was dismissed for the day.
Day 2 began with a summary of the previous day’s discussion, followed by an open forum consisting of a discussion on recommendations for the use of BDQ. The group was dismissed at 12 noon.
Based on the discussion and recommendations from the consultancy, CDC guidance will be issued. CDC/DTBE will work closely with partners to ensure that an enhanced monitoring system is in place for tracking patients who receive BDQ.
—Reported by Sundari Mase, MD, MPH
Div of TB Elimination