Nix-TB Clinical Trial Success: TB Alliance Secures FDA Approval for New Fight Against Tuberculosis Battle

Nix-TB Clinical Trial Success TB Alliance Secures FDA Approval for New Fight Against Tuberculosis Battle

The TB Alliance sponsored a successful clinical program leading to the FDA approval of pretomanid, a novel compound that will help in the fight against one of the world’s deadliest killers thriving especially in poor regions—drug-resistant tuberculosis (TB). The new drug was approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs (LDAP pathway) as part of a three-drug, six-month, all-oral regimen for the treatment of people with extensively drug resistant TB (XDR-TB) or multidrug-resistant TB (MDR-TB) who are treatment intolerant or non-responsive (collectively highly drug resistant TB).

What is the LDAP Pathway?

Established by the FDA, it is a tool to encourage further development of antibacterial and antifungal drugs to treat serious, life-threatening infections that affect a limited population of patients with unmet needs.

The Nix-TB Clinical Trial

The three-drug regimen consisted of bedaquiline, pretomanid and linezolid—collectively referred to as the BPaL regiment—was studied in the pivotal NIX-TB trial across three sites in South Africa. The study sites enrolled 109 people with XDR-TB as well as treatment-intolerant or non-responsive MDR-TB.

The Results

Nix-TB data has evidenced a successful outcome in 95 of the first 107 patients after six months of treatment with BPaL and six months of post-treatment follow up. For two patients, treatment was extended to nine months. The new drug applications contains data on 1,168 people who have received pretomanid in 19 clinical trials that have evaluated the drug’s safety and efficacy. Pretomanid has been clinically studied in 14 countries.

TB Treatment

TB, in all forms must be treated with a combination of drugs—the most drug sensitive forms of TB require six months of treatment using four anti-TB drugs. Treatment of XDR-TB or treatment-intoleration/non-responsive MDR-TB has historically been lengthy and complex, most XDR-TB patients currently take a combination of as many as eight antibiotics, some involving daily injections, for 18 months or longer. Prior to recent introduction of new drugs for drug-resistant TB, the World Health Organization (WHO) has reported estimates for treatment success rates of XDR-TB therapy at approximately 34% and about 55% for MDR-TB therapy.

What is Pretomanid?

A new chemical entity and a member of a class of compounds known as nitroimidazooxazines. TB Alliance acquired the development rights to the compound in 2002. It has been developed as an oral tablet formulation for the treatment of TB in combination with bedaquiline and linezolid, two other anti-TB agents, and is now indicated for the use in a limited and specific population of patients.

Adverse Reactions

Adverse reactions reported during the NIX-TB trial of the BPaL regimen included hepatotoxicity,. Myelosuppression, as well as peripheral and optic neuropathy. The link offers additional safety information.

A Breakthrough

Pretomanid is only the third approved new anti-TB drug approved by the FDA in more than 40 years. It is the first to be developed and registered by a not-for-profit organization. Pretomanid was granted Priority Review, Qualified Infectious Disease Product, and Orphan Drug Status.

Innovative Public-Private Partnership

As a product development partnership, TB Alliance has collaborated with and received significant support from numerous governments, academia, philanthropic institutions, the private sector, civil society organizations, and other partners over the course of pretomanid’s development.

Availability on the Market

Pretomanid is expected to be available in the United States by the end of 2019. Additionally to the U.S. FDA, TB Alliance has submitted pretomanid as part of the BPaL regimen for review by the European Medicines Agency and has provided data to WHO for consideration of inclusion in treatment guidelines for highly drug-resistant TB.

Who is TB Alliance?

Formed in 2000, TB Alliance (formerly The Global Alliance for TB Drug Development) is a not-for-profit product development partnership (PDP) dedicated to the discovery and development of new, faster-acting and affordable tuberculosis (TB) medicines. Since its inception in 2000, TB Alliance has worked to grow the field of available treatments for TB and now manages the largest pipeline of new TB drugs in history. It was founded in Cape Town, South Africa, and has since expanded. It is headquartered in New York City and has a regional office in Pretoria.

Lead Research/Investigator

Francesca Conradie, Researcher, University of Witwatersrand, South Africa