Janssen Research & Development, LLC (Janssen) today 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-centre international randomized controlled trial to evaluate a standardized treatment regimen of anti-tuberculosis drugs for patients with MDR-TB.
Bedaquiline is a diarylquinoline antimycobacterial drug, developed in the laboratories of Janssen, indicated for use as part of an appropriate combination regimen for pulmonary multidrug-resistant tuberculosis (MDR-TB) in adult patients when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability. It is the first new specific treatment for TB launched in several decades, and has a unique mechanism of action that inhibits mycobacterial ATP (adenosine 5’triphosphate) synthase, an enzyme that is essential for the generation of energy in Mycobacterium tuberculosis.
Janssen is working with The Union, the sponsor of the study, and the study’s principal investigators from the UK 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 the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) and is accepted by both health authorities as an alternative to the initially planned Phase 3 trial of SIRTURO®.
The EU prescribing information for bedaquiline includes a black triangle meaning it is subject to additional monitoring. The ‘Warnings and Precautions’ section in the Prescribing Information provides information regarding increased risk of mortality, occurrence of QT prolongation, risk of hepatic-related adverse drug reactions, drug interactions, use in HIV-TB co-infected patients, and use in patients with lactose intolerance and lactase deficiency. The most common adverse drug reactions seen in clinical trials were nausea, arthralgia, headache, vomiting and dizziness.
STREAM opened for recruitment in July 2012, with ‘Stage 1’ results expected 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 the STREAM study.
To date, bedaquiline 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.