ZeNix trial shows effectiveness of BPaL regimen for TB can be maintained with reduced dosing of Linezolid

The results of ZeNix, a phase-III clinical trial that took place in 11 sites across Georgia, Moldova, Russia and South Africa, revealed that the BPaL treatment remains effective against highly drug-resistant strains of tuberculosis (TB) with reduced dosage and/or duration of the Linezolid component of the regimen. Along with the maintenance of efficacy, there was a decrease in Linezolid-associated side effects that accompanied the reduced dosage or duration of Linezolid. The results from the trial, which was led by TB Alliance, were published in the New England Journal of Medicine, a statement from TB Alliance has said.

The BPaL regimen—which combines the antibiotics Bedaquiline (B), Pretomanid (Pa) and Linezolid (L)—received its first regulatory approval by the US Food and Drug Administration (FDA) in August 2019 as a six-month, three-drug, all-oral regimen for the treatment of people with multidrug-resistant TB, who are treatment intolerant or non-responsive as well as extensively drug-resistant TB (as defined by WHO prior to 2021). Historically, treatment of such forms of TB would take 18 months or longer, with reported global success rate of 52 per cent. BPaL has now been procured by more than 30 countries around the world, added the statement.

“These results add to the substantial evidence base for the efficacy and safety of the BPaL regimen and will enable care providers to further optimise use of the regimen,” said Mel Spigelman, MD, President and CEO, TB Alliance, in the statement, which developed Pretomanid and pioneered the use of the regimen.

He added, “We will continue to innovate and fight for access until the days of lengthy and highly toxic therapies are over for every person with TB.”

The statement also noted that a government-led study of the regimen in India called mBPaL commenced in October 2021, and is now enrolling patients at three sites out of a planned. It is scheduled to reach its primary completion in 2023 after enrolling 400 patients.

In addition, it mentioned that ZeNix was a four-arm, randomised study that enrolled 181 participants. Of these participants, 36 (20 per cent) were HIV-positive. Participants were treated for six months with Bedaquiline, Pretomanid and varying doses and durations of Linezolid, with follow up until the primary endpoint six months after completion of treatment. The study, which was double-blinded as to dosage and duration of Linezolid, sought to evaluate whether the efficacy of the BPaL regimen could be maintained while reducing a patient’s exposure to Linezolid and its a