A movement to promote and conduct research on the treatment and prevention of drug-resistant tuberculosis, with a commitment to address the substantial existing gaps in our knowledge and to help provide access to an effective cure and prophylaxis of drug-resistant tuberculosis throughout the world.
Nearly nine million people will develop tuberculosis (TB) in the world this year; at least 500,000 of these cases will have multidrug-resistant tuberculosis (MDR-TB). Some will receive treatment. However, we know little about the best ways of treating drug-resistant TB (DR-TB) and preventing tuberculosis in people who come in contact with DR-TB patients. Lacking a strong scientific basis in prescribing treatment regimens, existing TB treatments are often ineffective. TB control efforts require new evidence-based knowledge about optimal treatment regimens, prophylaxis, and, possibly, regimens involving new TB drugs, in order to address the growing health threats of MDR-TB and extensively drug-resistant (XDR) TB.
Update on AZD-5847 at the Union
World Conference on Lung Health
An update on AZD-5847 was presented at the Union World Conference on Lung Health in Cape Town, South Africa on Saturday, December 5th. In this EBA study, 4 doses of AZD-5847 were studied: 500 mg QD, 500 mg BID, 800 mg BID and 1200 mg QD. 15 patients were enrolled per arm; patients were HIV-uninfected or HIV-infected with CD4 count >350. Minimal antituberculosis activity was seen in the 500 mg BID dose and 800mg BID dose arms. Drug absorption was confirmed by PK studies, which suggested that BID dosing was more likely to be effective than QD dosing. Two Grade 4 adverse events occurred in the 800 mg BID arm, one case of hepatitis and one case of thrombocytopenia/anemia. The investigators concluded that the drug was minimally effective in EBA at the BID doses.
AZD-5847 was minimally effective at the doses studied, but study of higher doses is likely not warranted, given the toxicity that occurred with the doses studied here. AZD-5847 appears to have a toxicity profile similar to linezolid. Therefore, AZD-5847 does not appear to be a promising candidate to replace linezolid in treatment of drug-resistant TB.
Early bactericidal activity of azd5847 in pulmonary tuberculosis – Jennifer J. Furin, Jeannine Du Bois, Elana van Brakel, Phalkun Chheng, Amour Venter, Charles A. Peloquin, Bonnie Thiel, Sara M. Debanne, W. Henry Boom, Andreas H. Diacon, John L. Johnson (USA / South Africa) (link to conference listing)
Recent News and Announcements
Please join us on Friday, January 29th from 09:00 to 10:00 EST (15:00-16:00 CET) for a presentation from Novartis Pharma’s Roxana Drake, MD PhD entitled Clofazimine –Repurpose & Strategy The presentation will focus on the current status of clofazimine and on its development as an MDR-TB drug. The study design and rationale for clofazimine dose selection will be presented. Please see below […]
The report of the first Global MDR-TB Clinical Trials Landscape meeting was published in BMC Proceedings in November 2015. The meeting in December 2014 convened sixty international experts who met in Washington D.C. and Cape Town, South Africa to strategize coordination of research and development of new treatment regimens for MDR-TB. During the meeting, key MDR-TB trial-related issues were […]
The NExT trial, an open-label RCT to evaluate a new treatment regimen for patients with MDR-TB, was approved in South Africa by the Medicine Controls Council in June and enrolled its first patient this month. The NExT trial aims to evaluate the impact of a new injection-free six-to-nine month treatment regimen of linezolid, bedaquiline, levofloxacin, pyrazinamide […]
Cycloserine, an important drug used in regimens for the treatment of MDR-TB, increased in price last week from $500 to $10,800 for 30 capsules. The price increase came after the drug was acquired by Rodelis Therapeutics from The Chao Center. Following a swift response from providers, advocates, and policy makes, the drug was reacquired by the […]
Treatment Action Group and i-Base released the 2015 Pipeline Report for HIV, HCV, and TB, entitled “Drugs, Diagnostics, Vaccines, Preventive Technologies, Research Toward a Cure, and Immune-Based and Gene Therapies in Development.” The Pipeline Report summarizes progress and activities in HIV, Hepatitis C, and tuberculosis research. View the Pipeline Report here.