FDA approves pretomanid for drug-resistanttuberculosis

The FDA has announced its approval of PaMZ (pretomanid), from TB Alliance, a new drug developed to treat Extensively Drug-Resistant Tuberculosis (XDR-TB) and treatment intolerant/non-responsive Multidrug-Resistant (MDR) TB. Pretomanid is only the third anti-TB drug approved by FDA in more than 40 years. Prior to the pivotal Nix-TB trial of pretomanid as part of a three-drug regimen with bedaquiline and linezolid (known as the BPaL regimen), treatment for XDR-TB required a two-year regimen and in South Africa, for example, only cured 2 to 22 percent of those receiving treatment. The six-month, all-oral BPaL regimen cured approximately 9 out of 10 participants of the XDR-TB patients in the trials conducted in South Africa.

The FDA also approved pretomanid in combination with bedaquiline and linezolid for treating a limited and specific population of adult patients with extensively drug resistant, treatment-intolerant or nonresponsive multidrug resistant pulmonary TB. Multidrug-resistant TB and extensively drug-resistant TB are difficult to treat due to resistance to available therapies. According to the World Health Organization, in 2016, there were an estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB.

The safety and effectiveness of Pretomanid, taken orally in combination with bedaquiline and linezolid, was primarily demonstrated in a study of 109 patients with extensively drug-resistant, treatment?intolerant or non-responsive multidrug-resistant pulmonary TB (of the lungs). Of the 107 patients who were evaluated six months after the end of therapy, 95 (89%) were successes, which significantly exceeded the historical success rates for treatment of extensively drug resistant TB.

The most common adverse reactions observed in patients treated with Pretomanid in combination with bedaquiline and linezolid included damage to the nerves (peripheral neuropathy), acne, anemia, nausea, vomiting, headache, increased liver enzymes (transaminases and gamma-glutamyltransferase), indigestion (dyspepsia), rash, increased pancreatic enzymes (hyperamylasemia), visual impairment, low blood sugar (hypoglycemia), and diarrhea.

Comment: TB Alliance acquired the license to pretomanid, then known as Pa-824, in 2002. RTI assisted TB Alliance in planning and managing the preclinical studies needed for development and preparing the successful Investigational New Drug (IND) application to FDA in 2005, leading to the start of clinical trials that year.