South Africa’s Medicines Control Council (MCC) is set to continue denying compassionate use or pre-approval access to a TB drug that for many drug resistant patients remain their last hope.
If the MCC would agree, bedaquiline (TMC207) could be made available with reasonable conditions, to patients with extensively drug-resistant TB, who have limited further treatment options, before the drug is approved by regulatory autorities. In South Africa the obvious mechanism for doing this would be through Section 21 authorisation approved by the MCC.
MCC spokesperson Popo Maja declined to reveal any details on the MCC meeting last week other than to confirm that there had been a meeting and that “the applicant for bedaquiline access is the Directorate of TB in the National Department of Health”.
“It is not normal practice for the MCC to divulge our clients information. The matter was on the agenda of MCC and the outcome has already been communicated to the applicant. We are awaiting for the client's response,” he said.
Activists are in agreement that making medicines available to patients before they are properly tested, evaluated and approved is not something that the MCC can do at a whim.
“Nevertheless, we believe the arguments for making bedaquiline available are compelling and outweigh the concerns,” they said in a statement last month.
In a recent analysis of over 9 000 patients with multi-drug resistant (MDR) TB from 23 countries, 46% died, relapsed, failed treatment or defaulted.
Several studies of drug-resistant TB in South African settings have been published. In a study of a Durban cohort of 60 people with extensively drug resistant (XDR) TB, 25 (42%) died.
A study of the Tugela Ferry TB register for the years 2007 to 2009 found that at one year, mortality with XDR TB was 82% and with MDR TB it was 69%.
Patients on DR TB regimens typically take a regimen with many side effects and a poor evidence base for more than a year and a half and still only have a slightly better than a 50% chance of a successful treatment outcome. Mortality and morbidity are extremely high.
Given this situation, there is a belief that it is reasonable for patients in whom standard DR TB treatment is inadequate to consider taking experimental medicines that have some good quality safety and efficacy evidence.
“The MCC should be more open to considering compassionate access for people facing high morbidity or mortality due to failure of current best approved treatments. This is not a frequent situation. It no longer applies to diseases like HIV or diabetes for example. But it does apply to drug-resistant TB,” the activists said.
In Europe and North America there are several pre-approval access precedents, particularly with antiretrovirals. For example, more than 35,000 people received didanosine before it was approved by the FDA in 1991. This was controversial but likely prolonged many lives. Other antiretrovirals were also available before approval.
In South Africa, lopinavir/ritonavir (branded as Aluvia or Kaletra) was made available to patients on Section 21 authorisation before the drug was registered.
Pre-approving access to bedaquiline would therefore not be an unprecedented step by the MCC.
Bedaquiline is not registered anywhere in the world, but its application for registration is being fast tracked in the United States and Europe seeking conditional approval to make it available.
Médecins Sans Frontières in South Africa have attempted to access bedaquiline for carefully monitored treatment of a select few patients with pre-XDR and XDR TB. However, several attempts by MSF to gain compassionate access have been declined by the MCC.
For many of these patients there is no other hope and bedaquiline, in combination with other existing TB drugs in an individually tailored regimen, offers a last chance of survival. A number of patients have died while waiting for compassionate access to be granted.
The World Health Organization is supporting compassionate access and has urged countries to bring their regulations in step to facilitate compassionate access, especially for DR TB patients.
Last year the MCC, without any explanation, reversed an initial decision to grant compassionate access to bedaquiline
Activists have been calling for pre-approval access for bedaquiline for selected patients as far back as 2009.