Medical Research Interview with:
Brian Dannemann, MD, FACP
Senior Director, JNJ Pharmaceutical Research and Development
Titusville, NJ 08560
MedicalResearch: What are the main findings of the study?
Dr. Dannemann : The final investigational 120-week results from the TMC207-C208 Phase 2 study demonstrated that bedaquiline (SIRTURO®) showed nearly twice an many patients in the bedaquiline group as in the placebo group were cured on the basis of the World Health Organization (WHO) outcome definitions for Multidrug-Resistant Tuberculosis which was statistically significant (38 of 66 patients [58%] and 21 of 66 patients [32%] respectively; p = 0.003).
MedicalResearch: Were any of the findings unexpected?
Dr. Dannemann : The efficacy findings were in line with what we were expecting – validation of the surrogate endpoint of sputum culture conversion at 24 weeks (78.8% versus 57.6%, respectively; P=0.008) as a reliable predictor of cure in pulmonary Multidrug-Resistant Tuberculosis. We were pleased to see the addition of bedaquiline to a background regimen resulted in statistically significant higher culture conversion rate over 120 weeks (62.1% versus 43.9%; P=0.035).
There were 10 deaths in the bedaquiline group (13%) and 2 in the placebo group (2%), with no causal pattern evident. What was surprising about this was the unexpectedly low mortality rate in the placebo group (2%) as compared to what was reported in a meta-analysis of 9153 individual patients with Multidrug-Resistant Tuberculosis treated in programmatic settings, with a mortality rate of 15%.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Dannemann : The addition of bedaquiline to a background regimen resulted in statistically significant higher culture conversion rate over 120 weeks, validating sputum culture conversion at 24 weeks as a reliable predictor of cure in pulmonary Multidrug-Resistant Tuberculosis.
- These latest data speak to Janssen’s commitment to improving global public health outcomes by prioritizing the appropriate use of bedaquiline and facilitating access in patients with the greatest unmet need. Use of bedaquiline should however, be reserved for when an effective treatment regimen cannot otherwise be provided. Bedaquiline should be administered by Directly Observed Therapy (DOT).
- The primary efficacy endpoint was time to sputum-culture conversion in liquid broth.
- The overall incidence of adverse events was similar in both groups. The most frequent adverse events were nausea, arthralgia and vomiting.
- There was a reduced risk of evolution to more resistant subtype in patients receiving bedaquiline versus patients receiving placebo.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Dannemann : Janssen has been in active discussions with regulatory authorities including the U.S. FDA and European Medicines Agency and additional external partners to identify the optimal way to generate additional clinical data to further substantiate the benefit-risk for SIRTURO®, and to further define its optimal use regarding the number and types of agents that are needed in combination, and its optimal treatment duration in those combinations.
- Janssen aims to evaluate the potential for shortened treatment regimens, which can eventually be translated into public health practice.
Andreas H. Diacon, M.D., Ph.D., Alexander Pym, M.D., Ph.D., Martin P. Grobusch, M.D., Ph.D., Jorge M. de los Rios, M.D., Eduardo Gotuzzo, M.D., Irina Vasilyeva, M.D., Ph.D., Vaira Leimane, M.D., Koen Andries, D.V.M., Ph.D., Nyasha Bakare, M.D., M.P.H., Tine De Marez, Ph.D., Myriam Haxaire-Theeuwes, D.D.S., Nacer Lounis, Ph.D., Paul Meyvisch, M.Sc., Els De Paepe, M.Sc., Rolf P.G. van Heeswijk, Pharm.D., Ph.D., and Brian Dannemann, M.D. for the TMC207-C208 Study Group