TB war gains new arsenal

A new compound has been granted conditional marketing authorization by the European Commission (EC) for treating highly drug-resistant forms of pulmonary tuberculosis (TB).

Called pretomanid, the novel compound was developed by TB Alliance, a nonprofit organization dedicated to finding faster acting and affordable drug regimens to fight TB. The new drug was authorized as part of a three-drug regimen for the treatment of adults with extensively drug-resistant TB (XDR-TB) or multidrug-resistant TB (MDR-TB) who could not tolerate or did not respond to previous treatment. The oral regimen has to be given to patients for 6 months.

The conditional authorization is imcumbent upon the completion of long-term follow-up of patients in the Nix-TB trial as well as completion of TB Alliance’s ZeNix trial ZeNix is an ongoing trial to test the safety and efficacy of various doses and treatment durations of the drug combination of linezolid plus bedaquiline and pretomanid (a combination known as BPaL) in participants with pulmonary TB, extremely drug resistant (XDR) TB, pre-XDR-TB or nonresponsive/intolerant multiple drug resistant (MDR)-TB.

According to Dr Mel Spigelman, president and chief executive officer of TB Alliance, the regimen will provide a new treatment option for patients with XDR- and MDR-TB infections in the European Union.

The BPaL regimen was tested in the Nix-TB trial. Nix-TB was a multicenter, open-label trial that enrolled 109 adults with XDR-TB, in addition to treatment-intolerant or non-responsive MDR-TB from three sites in South Africa. The trial results, published in the 5 March issue of New England Journal of Medicine, saw favourable outcomes in 90 percent of patients (95 percent confidence interval, CI, 83–95). The remaining 10 percent had unfavourable outcomes. [2020;382:893–902]

The primary efficacy endpoint of Nix-TB trial was incidence of an unfavourable outcome defined as treatment failure (bacteriologic or clinical) or disease relapse through follow-up until 6 months after the end of treatment. The majority of patients in the trial underwent the BPaL regimen for 6 months. In two patients, treatment was extended to 9 months.

Pretomanid is a new chemical entity belonging to  a class of compounds known as nitroimidazooxazines. It is delivered in the form of an oral tablet as part of the BPaL treatment regimen. The most common side effects noted with the BPaL regimen are peripheral neuropathy, nausea, anaemia, vomiting, headache, dyspepsia, acne, decreased appetite, increased levels of transaminases, gamma-glutamyl transpeptidase and amylase, rash, pruritus, abdominal pain, and musculoskeletal pain.

In Europe, TB alliance has an exclusive commercialization partner which is the global pharmaceutical company Mylan. Mylan will market pretomanid as part of the BPaL regimen.

Rajiv Malik, president of Mylan, said that Mylan had a long-standing commitment to fighting infectious diseases around the world. The company is looking forward to bringing the new treatment to patients across Europe and other countries, adding that the authorization by the EC is one step towards making TB treatment accessible to patients around the world.