No matter how carefully we use the antibiotics we have, drug resistant infections will continue to gain ground, forcing us to develop entirely new classes of antibiotics to defeat them. With the last new class introduced more than 20 years ago, we have reached a dangerous tipping point, with drug resistant infections expected to begin outpacing antibiotic innovation.
Last week, however, brought a rare and long-awaited breakthrough. After decades of stagnation, not one but two new first-in-class antibiotics were approved by the Food and Drug Administration within just a day of each other. Both offer urgently needed new oral treatment options for gonorrhea — a disease with 82 million new cases worldwide each year — and both work through novel mechanisms that are active against drug-resistant strains.
But there is something even more remarkable about one of these new drugs, zoliflodacin. It was developed through a new kind of not-for-profit research and development model. This was designed to do two things: ensure that the right antibiotics are developed — those with the greatest public health need — and in such a way that countries can get legitimate access to affordable (akin to generic) versions of the drug almost immediately.
Following its approval last week by the FDA, this new drug, zoliflodacin, will be marketed in the U.S. under the brand name Nuzolvence by Innoviva Specialty Therapeutics, the Massachusetts-based biotech company that owns the intellectual property. Nothing unusual there.
What is notable is that my organization, the Global Antibiotic Research & Development Partnership (GARDP), a publicly funded not-for-profit, co-developed zoliflodacin and is now taking steps to make zoliflodacin available globally.
FDA approves first new kind of drug to target gonorrhea in decades
With a focus on countries that have a high disease burden but would normally not get access to new antibiotics for more than a decade, GARDP’s aim is to increase the speed at which much-needed new drugs reach the people that need them. GARDP is now working with manufacturing and commercialization partners to get zoliflodacin approved and registered in other countries, starting with Thailand and South Africa, where clinical trials were conducted.
That means zoliflodacin could become available in Thailand within just a few months of it entering the U.S. market.
This is possible thanks to a novel kind of public-private partnership between GARDP and Innoviva Specialty Therapeutics. GARDP not only funded but also actually carried out the Phase 3 clinical trial for zoliflodacin. We also took on additional supporting research and critical aspects of zoliflodacin’s pharmaceutical development, commercialization, regulatory approval, and registration.
For a small biotech like Innoviva, with limited clinical resources, this approach provided a clear path for its drug to advance through development, and increased its chances of success while ensuring Innoviva retains key markets, which currently includes the U.S., European Union, U.K. and other high-income countries.
In return, GARDP gets the right to register and commercialize zoliflodacin in more than three-quarters of the world’s countries, including all low-income countries, most middle-income countries, and several high-income countries.
It’s a radical approach — and one in which everyone wins. With drug-resistant infections expected to increase by more than 70%, this is precisely what is needed. Antimicrobial resistance is escalating globally because people aren’t getting the antibiotic treatments they need. With gonorrhea, for example, prior to last week, there hadn’t been a new treatment for decades, with the three most recent attempts — delafloxacin, solithromycin, and gentamicin — all failing to get clinical approval.
The fact that zoliflodacin was approved is testament to how well the Phase 3 clinical trial was carried out. Involving 930 patients enrolled across 16 sites in five countries —Belgium, the Netherlands, South Africa, Thailand, and the U.S. —this was the largest gonorrhea trial ever undertaken. It was also one of the most geographically, demographically, and epidemiologically diverse. With participants including women, adolescents, and people living with HIV, the scale and breadth of this trial was designed to help ensure the results would be robust across different populations and resistance patterns.
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The approval of zoliflodacin and of Bluejepa (gepotidacin), GSK’s new antibiotic for treating urinary tract infections and gonorrhea, are both very positive steps. Not only do they offer hope to millions of patients around the world, but they demonstrate two approaches to get the antibiotics we need.
But the issue is far broader than gonorrhea. As things stand, only 90 antimicrobials are currently in clinical development, compared to more than 9,400 for cancer. Of these, just five are both innovative — either new classes or at least not variants of existing antibiotics — and target one of the World Health Organization priority pathogens, those that pose the greatest threat to public health.
Ultimately these are the antibiotics that are most needed if we are to turn the tide on antimicrobial resistance. Until not that long ago, that might have seemed like a tall order, the idea that new classes could be developed and made affordable and available like generic drugs. Zoliflodacin is proof that there is a way to achieve it.
Dr. Manica Balasegaram is executive director of the Global Antibiotic Research & Development Partnership (GARDP).
