Janssen Research & Development, LLC (Janssen) is collaborating with the International Union Against Tuberculosis and Lung Disease (The Union) so that SIRTURO® (bed aquiline) can be included in the STREAM Study, an ongoing trial to assess a standardized treatment regimen of anti-tuberculosis drugs for patients with multidrug-resistant tuberculosis (MDR-TB). MDR-TB is a tuberculosis resistant to isoniazid (INH) and rifampicin (RMP) which are the 2 most powerful anti-TB drugs.
Janssen labs developed bedaquiline, a diarylquinoline antimycobacterial drug indicated to be used as a part of a combination regimen for pulmonary MDR-TB in adults when an effective treatment regimen can’t be used because of resistance or tolerability issues. This is the first new tuberculosis treatment in decades and has an action mechanism that inhibits mycobacterial ATP synthase. ATP (adenosine 5’triphosphate) synthase is an enzyme essencial to Mycobacterium tuberculosis to generate energy.
The Union is the sponsor of the study and the principal investigators are from the UK Medical Research Council (MRC). Janssen is working with them to include 2 bedaquiline-containing treatment arms and to further assess its efficacy and safety in adult patients with pulmonary MDR-TB (STREAM Stage 2); a new treatment regiment and an all-oral option will be evaluated as well. The STREAM Stage 2 is as an alternative to the initially planned Phase 3 trial of SIRTURO, and is a part of the post-approval requirements from the Food and Drug Administration (FDA) and European Medicines Agency (EMA).
The EU requires additional monitoring in the prescribing information for bedaquiline. As noted in a recent press release: 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.” Nausea, vomiting, dizziness, arthralgia and headache are the most common adverse reactions to the drug seen in clinical trials.
Recruitment for STREAM opened in July 2012 with ‘Stage 1’ outcomes expected in 2017. Thanks to a grant from The United States Agency for International Development (USAID), The Union is funding the STREAM study. The protocols of the ‘STREAM Stage 2’ are being finalized and after all approvals are in place the trials will begin.
Janssen is prioritizing registration in countries with high MDR-TB rates to facilitate their access to bedaquiline. It has received approval in the United States, conditional approval in the European Union, approval in South Africa, South Korea, Philippines, and in Russia through a partnership with JSC Pharmstandard.