Experts are calling the preliminary results of a small trial in 109 South African patients “groundbreaking.” The drug regimen tested in the trial has shown a 90% success rate against a deadly plague: extensively drug-resistant tuberculosis (XDR-TB).
Tuberculosis has now surpassed AIDS as the world’s leading infectious cause of death, and the XDR strain is the ultimate in lethality. It is resistant to all four families of antibiotics typically used to fight the disease. Only a tiny fraction of the 10 million people infected by TB each year get this type, but very few of them survive it. Even among those who get typical treatment, the cure rate is only 34%.
Dr. Gerald Friedland, one of the discoverers of XDR-TB and now an emeritus professor at Yale’s medical school, called the study, nicknamed Nix-TB, “a wonderful trial” that could revolutionize treatment: “If this works as well as it seems to, we need to do this now.”
The treatment normally can be extraordinarily difficult. A typical regimen in South Africa requires up to 40 daily pills, taken for up to two years. Other countries rely on even older regimens that include daily injections of antibiotics that can have devastating side effects, including deafness, kidney failure, and psychosis. But in this trial, patients took only five pills a day for six months.
The pills contain just three drugs: bedaquiline, pretomanid, and linezolid, or BPaL. On Wednesday, the FDA effectively endorsed the approach, approving pretomanid, the newest of the three drugs used in the regimen.
Pretomanid is not owned by a drug company but by the TB Alliance, a nonprofit based in New York. Some advocacy groups argued at the time of the FDA approval that the drug had not been adequately tested. However, Dr. Mel Spigelman, the alliance’s president, argued that a full clinical trial would be both impractical and unethical.
“Put yourself in a patient’s position,” he said. “Offered a choice between three drugs with a 90% cure rate, and 20 or more with less chance of cure—who would consent to randomization?” Such a trial would cost $30 million and take five more years, he added, which would be “a very poor use of scarce resources.”
Pretomanid’s approval by the FDA marks the second time a drug is being approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs, a pathway advanced by Congress to spur development of drugs targeting infections that lack effective therapies.
In the Nix-B trial, of 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 XDR TB.
The most common adverse reactions included peripheral neuropathy, acne, anemia, nausea, vomiting, headache, indigestion, rash, elevated liver and pancreatic enzymes, visual impairment, hypoglycemia, and diarrhea.