New TB Combination Has Potential To Simplify and Shorten Therapy

Dr. Dan Everitt Senior Medical Officer, TB Alliance.MedicalResearch.com Interview with:
Dr. Dan Everitt
Senior Medical Officer, TB Alliance.

Medical Research: What are the main findings of the study?

Dr. Everitt: The NC-002 trial tested a new, three-drug TB combination therapy, consisting of PA-824 (a new chemical entity), moxifloxacin (a re-purposed drug, not yet approved for TB treatment), and pyrazinamide (an existing TB drug currently used in standard TB treatment). This regimen is known as “PaMZ” and was tested in both drug-sensitive and multidrug-resistant TB (MDR-TB patients).

In the eight-week trial, PaMZ killed more bacteria than standard therapy and did so at a faster rate, showing its potential to shorten therapy to as little as four months for drug-sensitive and some forms of MDR-TB. Additionally, the trial included HIV-positive patients and a formal statistical evaluation found no effect of HIV status on the outcome of the study.

Medical Research: Were any of the findings unexpected?

Dr. Everitt: Actually, to our satisfaction, the results of the trial were precisely as expected. Results of an earlier 2-week trial (NC-001) predicted the results of this 2-month trial (NC-002), which was a major finding and advances the understanding of how earlier trials predict later trials. This could help streamline TB drug development in the future. The forthcoming Phase 3 trial will test a full-course of treatment.

Medical Research: What should clinicians and patients take away from your report?

Dr. Everitt: The findings of this study should bring hope to patients and clinicians that breakthrough TB treatments that can transform the face of TB therapy could be available soon.

Today’s TB drug regimen takes too long to cure, is too complicated to administer, and can be toxic. Treatment for active, drug-sensitive TB consists of 4 medicines (known as first-line drugs) and is administered for a period of 6 to 9 months. Drug-resistant TB is difficult, complicated, and expensive to treat. Treatment relies on second-line drugs, and is commonly administered for 18 months or longer. It includes daily injections for six months, and often causes severe side effects.

If PaMZ successfully completes Phase 3 development, it represents a shorter, simpler, and more cost-effective option for many TB patients, the benefits of which will be realized by clinicians and health-systems as well.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Everitt: While this is a tremendously important and encouraging step forward in improving TB treatment, it is not the final step in PaMZ’s development. First, we need to ensure that there is sufficient funding and political will to enable PaMZ to complete the final stage of development.

Additionally, research and development of additional new TB regimens are needed. TB Alliance’s vision is to eventually develop a universal TB treatment that can treat the disease in one or two weeks, like most infections. That is not currently possible with the existing TB drug candidates.

Tuberculosis and TB research and development need to be recognized as global health and development priorities and receive the level of advocacy and financial support consistent with one of today’s the most significant threats to the health of people all around the world.

Citation:

International AIDS Conference abstract:

Randomized trial of the bactericidal activity of 8-weeks treatment with moxifloxacin, Pa-824, and pyrazinamide in drug sensitive and multi-drug resistant tuberculosis

Presented by Daniel Everitt (United States).

D. Everitt1, R. Dawson2, A. Diacon3, D. Burger4, R. Schall5, C. Van Niekerk6, A. Conradie6, C. Mendel1

1Global Alliance for TB Drug Development, R&D, New York, United States, 2University of Cape Town, Division of Pulmonology, Department of Medicine, Cape Town, South Africa, 3Stellenbosch University and Task Applied Sciences, Department of Medical Biochemistry, Cape Town, South Africa, 4University of Free State, and Quintiles, Bloemfontein, South Africa, 5University of Free State, Department of Biostatistics, Bloemfontein, South Africa, 6Global Alliance for TB Drug Development, R&D, Pretoria, South Africa

Last Updated on July 22, 2014 by Marie Benz MD FAAD