Pretomanid has been granted a conditional marketing authorisation by the European Commission (EC) for treating highly drug-resistant forms of pulmonary tuberculosis (TB).
The new drug was authorised as part of a three-drug, six month, all-oral regimen for the treatment of adults with extensively drug-resistant TB (XDR-TB) or multidrug-resistant TB (MDR-TB) who are treatment-intolerant or non-responsive.
Pretomanid is developed by the TB Alliance, a non-profit organization.
“This regimen provides a new treatment option for patients in the European Union with highly drug-resistant TB infections,” said Mel Spigelman, MD, President and CEO of TB Alliance in a statement.
The combination treatment of bedaquiline, pretomanid and linezolid – collectively referred to as the BPaL regimen – was studied in the pivotal trial entitled Nix-TB. The multicentre, open-label trial enrolled 109 adults across three sites in South Africa with XDR-TB as well as treatment-intolerant or non-responsive MDR-TB.
The Nix-TB trial demonstrated a favourable outcome in 90% of patients. 11 patients (10%) had an unfavourable outcome and 98 patients (90%; 95% confidence interval, 83 to 95) had a favourable outcome. The primary efficacy endpoint for the study was the 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.
Most patients in Nix-TB were treated with six months of the BPaL regimen. For two patients, treatment was extended to nine months. The application for this conditional marketing authorisation contains data on 1,168 adults who have received pretomanid in 19 clinical trials that have evaluated the drug’s safety and efficacy.
Pretomanid is a new chemical entity and a member of a class of compounds known as nitroimidazooxazines. The conditional authorisation requires the completion of long-term follow-up of patients in the Nix- TB trial as well as completion of TB Alliance’s ZeNix trial, which is evaluating the safety and efficacy of the BPaL regimen with varying doses and durations of the drug linezolid.
Currently, most XDR-TB patients are treated with a combination of as many as eight antibiotics, some involving daily injections, for 18 months or longer. The most recent WHO data indicate treatment success rates of approximately 39 percent for XDR-TB and 56 percent for MDR-TB.