The U.S. Food and Drug Administration’s approval of the first new drug to treat tuberculosis in nearly half a century and the agency’s first use of its accelerated approval process to speed availability of TB medicine comes with cautions, and with a direction of work yet to be done, agency officials and treatment advocates agree.
The drug Sirturo – bedaquiline, in previous releases – was approved Dec. 28 to treat the disease in adult patients whose drug-resistant strains of the disease leave no other options. It has been shown to speed and sustain conversion from positive to negative in tests for tuberculosis bacteria, reduce infectivity, and increase the cure rate among patients with multidrug-resistant TB in clinical trials.
But the drug also was linked to cardiac effects that have the potential to lead to fatal heart rhythm, according to the FDA. In addition, while two patients taking a placebo, along with a standard tuberculosis treatment regimen during trials died, nine patients taking Sirturo with the standard regimen died. This led the consumer advocacy organization Public Citizen to recommend strongly against approving the drug, citing “a mortality rate – clearly the most important clinically relevant outcome for a life-threatening disease – that was five times higher.” The group’s letter counts 10 deaths in the Sirturo arm of the study, including one car crash victim, and said that toxicity of the drug could not be ruled out among the five non-tuberculosis deaths, the remaining four of which, it said, were attributed to alcohol poisoning, hepatitis cirrhosis, septic shock, and a stroke.
At the same time, advocates for improved accessible tuberculosis treatment urged the FDA to approve the drug quickly, and continue to conduct trials to test the drug’s safety and long-term effectiveness.
In turn the FDA panel that reviewed the drug last month, while unanimous in finding evidence that the drug was effective, was sharply divided, voting 11 to 7 on evidence that the drug had been shown to be safe.
The fast-track approval will make the drug available to patients with no other treatment options while further testing of the drug is carried out. The drug will carry a warning alerting doctors and patients of the potential heart effect, as well as noting the deaths of patients taking the drug. The drug also carries side effects noted with other tuberculosis drugs that include nausea, joint pain and headache.
TAG – Treatment Action Group – one of the groups that called for the expedited approval, hailed the decision Monday, saying the move offers hope for patients with multidrug-resistant tuberculosis and demonstrates that the path exists to approve more treatments. The group is calling for the continued development of effective tuberculosis treatments, as well as the continued thorough testing of Sirturo in Phase three trials. The group is calling on drug maker Janssen to carry out the studies quickly, test the drug for interactions with HIV medicines, determine if it can be used to treatment children for whom other treatments do not work, and make the drug available at accessible prices.
“We have to remember the drug does work,” Colleen Daniels of TAG said.