The announcement Wednesday of U.S. Food and Drug Administration approval of pretomanid, a new tuberculosis drug that has been part of a ground-breaking treatment regimen against the deadliest and most resistant form of the disease represented a major step forward on multiple fronts, international treatment advocates agree.
One of only three new drugs receiving regulatory approval in the last decade, after a nearly half century lag in development of TB-fighting medicines, pretomanid was developed through a nonprofit partnership, forging a new path in a field that had been abandoned or neglected by large private pharmaceutical companies. The process through which it was approved — a streamlined “Limited Population Pathway for Antibacterial and Antifungal Drugs” established by the FDA to encourage development of drugs to treat life-threatening infections affecting a subset of patients with immediate needs — also demonstrated commitment to accelerated access to new medicines.
Most importantly, the three-drug regimen in which pretomanid had been tested, which also includes bedaquiline, the drug that in 2012 became the first new anti-tuberculosis drug in 50 years to receive regulatory approval, and linezolid, a repurposed drug used normally for other resistant infections, demonstrated unprecedented effectiveness in clearing extensively drug resistant disease — XDR-TB — from patients in record-setting time. While other drug combinations had required two years of painful and debilitating treatment with discouragingly low rates of success, the three-drug regimen, tested in the Nix-TB study, cleared the disease from more than 90 percent of patients in six months.
Representing what Nix-TB study leader Dr. Francesca Conradie called “a phenomenal breakthrough in the treatment for XDR TB,” the regimen has offered evidence-backed hope for people sick with the world’s deadliest infectious disease.
The path of safe and effective tuberculosis drug development, too long-abandoned, and still strewn with obstacles to success, access and profit, remains complicated, though. On Wednesday, noting that pretomanid is only the second new TB drug to receive FDA approval in decades (the third drug receiving regulatory approval in the last five years, delamanid, was approved by the European Medicines Agency), a statement from the Treatment Action Group said the approval of the medicine to be included in the three-drug regimen against XDR-TB and treatment intolerant drug-resistant tuberculosis, “represents a milestone in TB treatment development.” But it also called for additional research on the drug.
Unlike the agency’s 2914 conditional approval of bedaquiline, Lindsay McKenna of the group noted today, the approval of pretomanid requires no further research, leaving information about the drug’s safety and effectiveness still limited, with a possibly damaging precedent set. Begun at a time when options for patients with extensively drug-resistant disease were more limited, the study did not have a control arm she noted, also leaving uncertain the weight of the role pretomanid played in the regimen.The development of a new drug against TB and a successful regimen is “fantastic,” McKenna said. It leaves, she added, “other research questions we’d like to see answered. We’re not sure they will be.”