The U.S. Food and Drug Administration’s approval of a new tuberculosis antibiotic this month could be a significant win not only for TB patients, but for a burgeoning nonprofit model for developing prescription drugs.
Tuberculosis kills about 1.6 million people per year worldwide, and drug-resistant strains of the disease are becoming more common, making it difficult to treat. The new antibiotic, called pretomanid and developed by the nonprofit TB Alliance, achieved a 90 percent success rate among patients with highly drug-resistant forms of TB who took the antibiotic as part of a three-drug, all-oral regimen over a six month period.
If it were not for TB Alliance’s nonprofit mission, the drug might not exist because for-profit companies have focused their efforts elsewhere.
“There has been an exodus from the antibiotic business,” said Allan Coukell, an antibiotic expert at The Pew Charitable Trusts.
In February, The Pew Charitable Trusts joined a group of other shareholders representing public health and antibiotic developers in urging Congress to consider economic incentives for antibiotics, in order to reboot a market that almost all the large pharmaceutical companies have left.
Antibiotic discovery, research trials and FDA approval is expensive. The cause of the pharmaceutical exodus from the antibiotic market lies in the lack of economic incentives to invest in a final product that is frequently unprofitable.
“You either have to have big donor or a revenue model that keeps you investing in discovery and development,” said Coukell. “Right now that doesn’t exist.”
In recent decades, pharmaceutical funding has been put toward drug research and development that will yield higher revenue, such as cancer drugs.
This is in part because cancer drugs or drugs for chronic illnesses are put to use immediately and taken for long periods of time, whereas new antibiotics are used for a set period of time and only replace what’s currently on the market when absolutely necessary, to avoid building-up drug resistance.
Truvada, the HIV treatment that was the 20th best-selling drug in 2018, brought in $2.6 billion in sales that year. By contrast, the 2018 sales of all branded antibiotics was only $540 million, according to Needham & Company, LLC.
TB Alliance was able to develop its newest drug because it relies on a variety of donors from all around the world, including the Bill & Melinda Gates Foundation and USAID.
“What that allows us to do is to take away — from the ultimate pricing of a drug — the risk and cost of doing the research and development,” said TB Alliance CEO Mel Spigelman.
Some medical professionals say the only sustainable model for antibiotics in the current drug market are nonprofits with endowments like TB Alliance. That funding can cover basic operational costs and allow for an often lengthy and tedious discovery process for antibiotics and drugs that are needed but aren’t profitable.
“A for-profit motive does not work,” said Brad Spellberg, Chief Medical Officer at the Los Angeles County USC Medical Center and author of a New England Journal of Medicine paper on Sustainable Discovery and Development of Antibiotics. “We need rich donors or government to recognize that it may be a better investment to spend $1 billion dollars to endow three nonprofits in this space than to repeatedly spend a billion dollars pumping up the profits of antibiotics that hit the market.”
The idea is catching on globally. Nonprofits like the UK-based Global Antibiotic Research and Development Partnership and Medicines for Malaria Venture, which focuses on antimalarial drugs, are using similar models as TB Alliance in an effort to develop drugs for diseases that have been largely ignored by traditional pharmaceutical companies.
But many nonprofits must still work with for-profit companies and other institutions to fulfill their mission.
TB Alliance, which does not have its own laboratories and staffs only 50 full-time employees, strives to cut costs by partnering with laboratories at academic institutions or contracting outside research organizations. It also has relationships with for-profit pharmaceutical companies to conduct studies on toxicology, chemical combinations and dosage, as well as physically manufacture the drugs.
Convincing for-profit companies to contribute to unprofitable treatments, even tangentially, is not easy. TB Alliance said it struggled initially to find a company willing to manufacture the drug even though the nonprofit paid for the research and development. But in April, it was announced that pretomanid had been licensed to the generic pharmaceutical company Mylan.
Its next goal is getting the FDA-approved drug approved in other countries– the antibiotic is currently being evaluated by the World Health Organization.
“We still have a lot of work cut out for us,” said Spigelman. “But we are thankful that we have come up with showing, I believe, that with proper investment and with proper drugs that drug- resistant TB certainly doesn’t have to be a death sentence.”