Sirturo has been approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients, thus providing patients earlier access to promising new drugs while the company conducts additional studies to confirm the drug’s clinical benefit and safe use. The drug demonstrated the potential to fill an unmet medical need, has the potential to provide safe and effective treatment where no satisfactory alternative therapy exists, and is intended to treat a rare disease. Sirturo’s manufacturer, Janssen Therapeutics, will distribute the drug from a single source and will provide educational materials to help ensure the drug is used appropriately.
As of now, Sirturo’s safety and effectiveness have been established in 440 patients in two Phase 2 clinical trials. Patients in the first trial were randomly assigned to be treated with Sirturo plus other drugs used to treat TB, or a placebo plus other drugs used to treat TB. All patients in the second trial, which is on-going, received Sirturo plus other TB drugs. Both studies were designed to measure the length of time it took for a patient’s sputum to be free of M. tuberculosis (sputum culture conversion, or SCC). Results from the first trial showed patients treated with Sirturo combination therapy achieved SCC in a median time of 83 days, compared with 125 days in patients treated with placebo combination therapy. Results from the second trial showed the median time to SCC was 57 days, supporting the efficacy findings of the first trial. Common side effects identified in the clinical trials included nausea, joint pain, and headache.
Although bedaquiline appears effective at killing TB bacteria quickly in early and mid-stage clinical trials of people with MDR-TB, TB activists have rightly called for the FDA to require appropriate phase III trials—especially those that include HIV-positive TB patients taking anti-retroviral drugs, who have not yet been studied on the drug—quickly and thoroughly. Studies of bedaquiline in children, and drug interaction studies with other new and existing drugs in the TB and HIV pipelines, are also necessary. Nathan Geffen from activist group Treatment Action Campaign in South Africa cautions that, “It is essential that phase III trials be conducted to ensure the drug’s safety and benefit in terms of survival.”
Bedaquiline’s manufacturer must also commit to carrying out these studies rapidly. They also must price the drug so that it is accessible in both the low- and middle-income countries that disproportionately bear the burden of TB, and the low-incidence settings where TB programs receive few resources. For bedaquiline to make an impact in preventing unnecessary TB deaths and suffering, regulators in other countries must swiftly build their capacity to review and approve new drugs, and enable them to reach those in need as quickly as safety permits. Countries must also build their capacity to roll out new drugs for MDR-TB.
“By granting accelerated approval of bedaquiline, the FDA has sent a clear signal that there is hope for people with MDR-TB, and that fighting TB is a priority,” said Mark Harrington, Executive Director of TAG. “Over one million people need new TB drugs this year, and the FDA’s approval shows that there is a clear regulatory pathway for approving new TB treatments and regimens. In order for bedaquiline to continue to be effective, and lives to be saved, we will need new, safer and better companion drugs. This historic occasion must mark a new beginning for TB drug development.”
Currently MDR TB affects over a million people worldwide, less than 5% of whom are able to receive proper treatment. Treatment success rate in those who receive treatment is less than 50%.
Citizen News Service - CNS
January 2013
