Janssen announced a collaboration with the International Union Against Tuberculosis and Lung Disease (The Union) to include SIRTURO (bedaquiline) in the STREAM study. The STREAM study is an ongoing, multi-center international randomized controlled trial to evaluate a standardized treatment regimen of anti-tuberculosis drugs for patients with multidrug-resistant tuberculosis.
Janssen is working with The Union, the sponsor of the study, and the study’s principal investigators from the United Kingdom Medical Research Council (MRC) on an amendment to their current protocol to include two bedaquiline-containing treatment arms to further assess safety and efficacy in adult patients with pulmonary MDR-TB and also to evaluate a new treatment regimen, including an all-oral option. The amendment, which will include the two bedaquiline-containing treatment arms, will be known as STREAM Stage 2. STREAM Stage 2 is part of the post-approval requirements for bedaquiline from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and is accepted by both health authorities as an alternative to the initially planned Phase 3 trial of sirturo.
Bedaquiline is a diarylquinoline antimycobacterial drug indicated as part of combination therapy in adults with pulmonary MDR-TB. Use of bedaquiline should be reserved for when an effective treatment regimen cannot otherwise be provided. Bedaquiline should be administered by directly observed therapy (DOT). The indication is based on analysis of time to sputum culture conversion from two controlled Phase 2 trials in patients with pulmonary MDR-TB. The safety and efficacy of bedaquiline for the treatment of drug-sensitive TB, latent infection due to Mycobacterium tuberculosis and for the treatment of infections caused by non-tuberculous mycobacteria (NTM) have not been established. In addition, there are no data on the treatment with bedaquiline of extrapulmonary TB (e.g., central nervous system). Therefore, use of bedaquiline in these settings is not recommended.
The U.S. prescribing information for bedaquiline includes Boxed Warnings regarding increased risk of death and occurrence of QT prolongation. The Warnings and Precautions section provides additional information regarding these risks and includes risk of hepatic-related adverse drug reactions, drug interactions, use in HIV-TB co-infected patients and treatment failure. The most common adverse drug reactions were nausea, arthralgia and headache. Additional adverse events include hemoptysis and chest pain.
STREAM opened for recruitment in July 2012, with Stage 1 results estimated in 2017. Details of the STREAM Stage 2 study protocol, which will include bedaquiline, are being finalized. The study sponsors are eager to begin STREAM Stage 2 and plan to begin immediately after all requisite approvals are in place. The Union, through a grant from The United States Agency for International Development (USAID), is currently funding STREAM Stage 1 with additional support from the UK MRC and the UK Department for International Development (DFID).
To date, sirturo has received accelerated approval in the U.S., conditional approval in the European Union, approval in South Korea, South Africa and the Philippines, and is registered in the Russian Federation through a partner for the Russian Federation and CIS countries, JSC Pharmstandard. Regulatory filings have been submitted in China, Colombia, India, Peru, Thailand and Vietnam. Janssen is prioritizing registration in high MDR-TB burden countries to facilitate access to bedaquiline as soon as possible.
Date: November 6, 2014
Source: PR Newswire
Filed Under: Drug Discovery