Global health groups reached out to the Medicines Control Council (MCC) in South Africa Thursday advocating “compassionate use” of an exploratory multidrug-resistant tuberculosis (MDR-TB) treatment known as TMC-207 or bedaquiline. The compassionate use concept allows patients access to promising new drug candidates in clinical trials when current treatment options have proven unsuccessful and is endorsed by the World Health Organization as a priority for addressing the extensively drug-resistant (XDR)-TB epidemic.
So far Medicines Sans Frontieres (MSF, or Doctors without Borders) and Treatment Action Group (TAG) have spearheaded sign-on letters to the MCC describing the desperate situation facing South Africans with MDR-TB and those who might become infected. South Africa has one of the worst TB epidemics in the world, fueled by the high prevalence of HIV. According to the MSF letter, approximately 10,000 people are diagnosed with MDR-TB in the country every year, a substantial number of whom suffer from XDR-TB. Treatment with currently available regimens is only successful for about 60 percent of MDR-TB patients and 44 percent of XDR-TB patients.
“Many patients who are not successfully treated succumb to the disease quite rapidly, particularly those who are HIV infected. However, for the proportion of patients who remain alive, current treatment options are ineffective, thereby leading to treatment failure,” according to the MSF letter.
TMC-207 is part of the TB Alliance drug development portfolio and developed by Janssen, formerly Tibotec, a research subsidiary of Johnson & Johnson. From a new class of drugs called Diarylquinolines, TMC-207 is expected to be active against both drug-sensitive and drug-resistant TB bacteria. MSF’s letter explains that in a phase II clinical trial, the addition of bedaquiline to a standard MDR regimen for patients with drug resistant tuberculosis both reduced the time to conversion to a negative sputum culture and increased the proportion of patients with conversion to a negative sputum culture. The TAG letter highlighted a separate study which demonstrated adding bedaquiline to an individualized drug resistant TB regimen resulted in nearly 80 percent culture conversion after 24 weeks.
Janssen has made the drug available free of charge under compassionate use criteria since the middle of 2011.
The MCC apparently granted approval for compassionate use of TMC-207 to the Khayelitsha Drug Resistant TB Program in Cape Town in August 2011 – but in a verbal communication between the drug manufacturer and the MCC, that approval was withdrawn and Janssen has since been unwilling to supply TMC-207 to the program. MSF said in the letter that it had not received notification or rationale for the MCC decision, and called on the regulatory office to reverse the decision or provide written justification for their decision within the next two weeks. The MSF letter was signed by more than 40 doctors and other public health experts throughout South Africa, as well as the Southern African HIV Clinicians Society and MSF.
TAG sent a similar letter from the global community of advocates for TB-infected and TB-affected people requesting a response by May 11. Citing that bedaquiline has already been safely prescribed to nearly 50 patients in ten countries, the TAG letter argues that available scientific data is more than sufficient to justify compassionate use of the drug in South Africa. “Denying these patients access to bedaquiline is, in many cases, a death sentence. South Africa cannot afford to wait for results from as yet uninitiated Phase III studies to take action on providing access to bedaquiline,” according to the letter.