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Statement from Treatment Action Group on U.S. FDA Approval of Pretomanid

TAG welcomes simpler, shorter treatment options for people with some forms of drug-resistant tuberculosis, while urging additional research and equitable access

August 14, 2019 — Treatment Action Group (TAG) welcomes the advent of shorter, simpler treatment for the most difficult to treat forms of drug-resistant tuberculosis (DR-TB). As only the second new TB drug to receive U.S. Food and Drug Administration (FDA) approval in the past two decades, pretomanid—which was approved for extensively and pre-extensively or treatment intolerant DR-TB, in combination with bedaquiline and linezolid—represents a milestone in TB treatment development.

However, given the limited evidence supporting the drug’s contribution to the regimen—in contrast to the other two drugs, whose potency against TB are relatively well-characterized—and the small and uncontrolled design of the trial on which the FDA’s decision was based, many questions remain about pretomanid and of the bedaquiline-linezolid-pretomanid regimen (referred to as the Nix-TB regimen or BPaL). TAG is especially concerned about how this approval has the potential to reduce regulatory standards for the development of future TB drugs and regimens intended to optimize the safety, duration, and efficacy of treatment regimens for DR-TB. These questions and concerns are elaborated in TAG’s testimony to the FDA Antimicrobial Drugs Advisory Committee,1 and the Global TB Community Advisory Board’s research, regulatory, and access considerations regarding pretomanid,2 TAG has also shared with the FDA our broader concerns about lowering the evidentiary bar for approval with the Limited Population Pathway for Antibacterial and Antifungal Drugs;3 pretomanid is the second drug approved under this new pathway.

“Many people with extensively or pre-extensively drug-resistant TB would welcome a three-drug, all-oral, six-month regimen with a high cure rates, and therefore would want the option to access pretomanid, along with bedaquiline and linezolid,” said Mark Harrington, TAG’s executive director. “However, we support remarks by members of the FDA Antimicrobial Drugs Advisory Committee that pretomanid’s approval should not be precedent-setting in terms of the small sample size and non-controlled design of its pivotal clinical trial, Nix-TB. Robust development programs based on randomized controlled trials must continue to be the required bar for new drug and regimen approval, even and especially for the world’s deadliest infectious disease, to ensure that those with TB receive treatment that meets the highest scientific standards for safety and efficacy.”

Many important questions also remain about the specifics of the non-profit TB Alliance’s oft-stated “Adoption, Availability, and Affordability” policy,4 especially in light of a non-transparent, license of pretomanid to the for-profit generic manufacturer Mylan. “Equitable access to TB medicines is a human right. As the developer of the third new drug for DR-TB in the past six years, TB Alliance should learn from both the positive examples and mistakes of Janssen and Otsuka’s introductions of bedaquiline and delamanid, respectively,” noted Lindsay McKenna, TAG’s TB project co-director. “Philanthropic and public funding underpinned pretomanid’s development; it must be treated as a public good. This means at a minimum: full transparency, broad registration, pre-approval access, and a low global price of $1/day, in keeping with research on cost of goods and calls for a $500 DR-TB regimen.5,6


1 TAG. Testimony to the FDA on New Drug Application for Pretomanid Tablets. Jun 6, 2019. http://www.treatmentactiongroup.org/content/tag-testimony-fda-new-drug-application-pretomanid-tablets

2 Global TB Community Advisory Board. Research, Regulatory, and Access Considerations Regarding Pretomanid. May 15, 2019. http://www.tbonline.info/media/uploads/documents/tb_cab_pretomanid_nda_considerations_final_05.14.19.pdf

3 TAG. Oral comment re: docket number FDA-2018-D-2032 Public Meeting on Limited Population Pathway for Antibacterial and Antifungal Drugs. July 12, 2019. http://www.treatmentactiongroup.org/content/tag-comments-delivered-fda-public-meeting-lpad

5 Gotham D, Fortunak J, Pozniak A, et al. Estimated generic prices for novel treatments for drug-resistant tuberculosis. J Antimicrob Chemother. 2017 Apr 1; 72(4): 1243-1252. doi: 10.1093/jac/dkw522.

6 Médecins Sans Frontières. Developing countries hit with high price for important new tuberculosis drug. 24 February 2016. http://www.msf.org/en/article/access-developing-countries-hit-high-price-important-newtuberculosis-drug 

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About TAG: Treatment Action Group (TAG) is an independent, activist and community-based research and policy think tank fighting for better treatment, prevention, a vaccine, and a cure for HIV, tuberculosis, and hepatitis C virus. TAG works to ensure that all people with HIV, TB, or HCV receive lifesaving treatment, care, and information. We are science-based treatment activists working to expand and accelerate vital research and effective community engagement with research and policy institutions. TAG catalyzes open collective action by all affected communities, scientists, and policy makers to end HIV, TB, and HCV.