In August 2019, Pretomanid, drug developed by the non-profit organization, TB Alliance, has received U.S. Federal Drug Administration (FDA) approval for treatment of extensively drug-resistant tuberculosis or treatment-intolerant/non-responsive multidrug-resistant tuberculosis in combination regimen with bedaquiline and linezolid.
Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to at least isoniazid and rifampin, the two most potent TB drugs.
Extensively drug-resistant tuberculosis (XDR-TB) is a rare type of multidrug-resistant tuberculosis that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).
This approval represents a historical victory for people suffering from these highly drug-resistant forms of the world’s deadliest infectious disease. It is only the third new anti-TB drug approved for use by FDA in more than 40 years, as well as the first to be developed and registered by a non-profit organization.
Before this treatment regimen, people infected with highly drug-resistant TB had poor treatment options and a poor prognosis.
The three-drug regimen consisting of bedaquiline, pretomanid and linezolid – collectively referred to as the BPaL regimen – was studied in the pivotal Nix-TB trial across three sites in South Africa. The trial enrolled 109 people with XDR-TB as well as treatment-intolerant or non-responsive MDR-TB.
Nix-TB data have shown a successful treatment outcome in 95 of 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 application 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. Adverse reactions reported included hepatotoxicity, myelosuppression, as well as peripheral and optic neuropathy.
Tuberculosis is usually treated with combination of drugs. Drug-susceptable forms of TB require six months of treatment using four anti-TB drugs. Treatment of XDR-TB or treatment-intolerant/non-responsive MDR-TB was very complex. Patients currently take a combination of eight antibiotics, some involving daily injections, for 18 months or longer. Based on World Health Organization (WHO) estimates, treatment success rates of XDR-TB are approximately 34% and about 55% for MDR-TB.
“This new regimen provides hope with 9 out of 10 patients achieving culture negative status at 6 months post-treatment with this short, oral regimen.”
Pretomanid is expected to be available in the United States by the end of this year. In addition 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 the WHO for consideration of inclusion in treatment guidelines.
- Pretomanid and BPaL. Full Prescribing Information. August 2019.
- TB Alliance. Pretomanid and BPaL Regimen for Treatment of Highly Resistant Tuberculosis. Oral presentation at: Antimicrobial Drugs Advisory Committee; June 6, 2019; Silver Spring, MD.
- The Review on Antimicrobial Resistance. Tackling Drug- Resistant Infections Globally. May 2016.
- World Health Organization (WHO). Global TB Report 2018.
- Fox W. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council Tuberculosis Units. Int J Tuberc Lung Dis. 1999;3(10):S231-S279.