Tuberculosis is the world’s deadliest infectious disease: Between 2007 and 2017, an estimated 94.5 million people caught tuberculosis, and more than 14 million died from it. Rising numbers are being infected by strains of the disease that are resistant to all known antibiotics. Yet until recently, no new classes of drugs for tuberculosis had been brought to market for 46 years. Against this dire background, a rare piece of good news came this week from the Food and Drug Administration, which Wednesday approved a new drug, Pretomanid, for treating patients with highly drug-resistant tuberculosis. It was the first time a non-profit research organization, TB Alliance, had developed a new treatment, sponsoring clinical trials all the way through FDA approval. This success story points to the potential for future public-private partnerships to meet the urgent need for new therapies for infectious disease. The approval of Pretomanid hinged on results from the Nix-TB trial, which included clinical trials at three sites in South Africa, involving 109 patients with highly resistant tuberculosis. The cure rate was 89%. “Without a doubt, this marks a watershed in our treatment of drug-resistant TB,” said Francesca Conradie, a researcher at the University of Witwatersrand who served as chief investigator in the trials. “If we play our cards right, extensively drug-resistant TB will be a thing of the past within 15 years.”
Tuberculosis has afflicted humanity for thousands of years. The Greeks called it phthisis (wasting away), while later generations of Europeans and Americans knew it as the great white plague or consumption. The microbe that causes the disease, Mycobacterium tuberculosis, was discovered in 1882 by Robert Koch, but it took another six decades to discover streptomycin, an antibiotic cure. In time the microbe developed resistance, first to streptomycin and then to the few new drugs that followed. When Pauline Howell, the senior medical officer at one of the three South African sites, began enrolling patients in the Nix-TB trial in 2015, her waiting room filled up with young people stricken with drug-resistant disease. “They were 18, 19, 20 years old, and had gotten infected through no fault of their own—just by breathing—on their way to school or work,” she recalled. “All of them expected to die.” For years, patients with highly resistant disease had been prescribed a two-year course of treatment that involved a total of up to 14,000 pills, along with painful injections that could result in deafness, psychosis and liver damage. Initially, Dr Howell felt sceptical that TB Alliance’s novel treatment, which required less than 750 pills in just six months of treatment, could succeed. But participants responded strikingly quickly to the new regimen.
“There’s still TB?” That is the question that Neil Schluger, Chief of Pulmonary Care at Columbia University Medical Center and one of the world’s top tuberculosis experts, says he often gets the question when he introduces himself in the U.S. The question reveals a sharp split: In the U.S. and Europe, the incidence of tuberculosis remains low and well-controlled, while across vast swaths of the rest of the world, it is a devastating contagion. (The worst-hit countries are India, China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa.) Dr Schluger faults the traditional model of drug research and development for the failure to invent new cures for tuberculosis. “Progress in HIV research far outpaced progress in TB and malaria,” he explained. Roughly 10 times more money is spent on developing new drugs for HIV than for tuberculosis. “Since there are significant numbers of HIV-infected persons in high-income countries, there’s a substantial market for those drugs, and companies can get a good return on their investment since treatment is lifelong.” Tuberculosis, in other words, gets shorter shrift because it is a curable rather than a chronic condition, and because most of the suffering takes place in poorer countries. A new model for drug research, tailored to long-orphaned diseases such as tuberculosis and malaria, could pair the depth of scientific knowledge among researchers from profit-making pharmaceutical companies with the public-health orientation of non-profit partners.
TB Alliance received support from governments, including Australia, Germany and Indonesia, and collaborates with universities as well as pharmaceutical giants such as Janssen, a division of Johnson & Johnson and Mylan. GlaxoSmithKline has collaborated on preclinical testing of a new compound with the Bill and Melinda Gates Foundation. (The foundation, which spun off a research arm of its own last year, is already the world’s second-largest investor in tuberculosis research, surpassed only by the combined contributions of eight U.S. agencies.) In October, French President Emmanuel Macron will host an international conference in Lyon that aims to raise $14 billion for the Global Fund to Fight AIDS, Tuberculosis and Malaria. Those funds would support public-health systems creaking under the weight of these modern plagues. It won’t do any good, after all, to invent new cures if more people aren’t diagnosed properly and offered appropriate treatment. What the world needs most is entrepreneurial ingenuity and sustained a commitment to match the scale of a preventable and ongoing catastrophe.
Credit: Douglas M. Foster for The Wall Street Journal, 16 August 2019. Mr Foster is an Associate Professor of Journalism at Northwestern University and the author of After Mandela: The Struggle for Freedom in Post-Apartheid South Africa (Liveright).