Without new antibiotic development, our society is doomed to reverse the last century of medical progress.
On Monday, life-science leaders and biotech investors will convene in San Francisco for the renowned annual JP Morgan Healthcare Conference. As usual, many deals, investments, collaborations, and partnerships will be announced that will shape the future of pharmaceutical development. With major patent cliffs looming, much of the focus will center around high-reward areas like obesity and cancer.
One area that will likely receive little attention is antibiotic development — despite its critical importance to the future of public health.
As we have all seen from the COVID virus, pathogens like bacteria, viruses, and to a lesser extent fungi, evolve and mutate at breakneck speed to develop resistance against treatments and vaccines. Yet our antimicrobial development, especially antibacterial, does not keep pace with this. Between 2017 and mid-2024, only 13 new antibiotics obtained market authorization, but only 2 of these represent a new chemical class and can be termed innovative. Meanwhile, resistance against our existing antibiotics is expanding fast. The OECD estimates that over 40% of bacterial infections in the G20 countries are already resistant to antibacterial treatments. As my kids would say, the math isn’t mathing.
Penicillin was discovered in 1928 but did not become widely available for treatment until the 1940s. Few of us remember a world without effective antibiotics. Here are a few examples of what a return to those days could mean:
Surgeries would be riskier: any optional surgery, joint replacements, and bowel operations would be too dangerous because of the risk of infections.
Childbirth would be more dangerous. Mothers and babies would routinely die in childbirth.
Infections will be more common: Tonsillitis and food poisoning could be life-threatening. In extreme cases, a paper cut could be fatal.
STIs would be incurable and deadly.
Tuberculosis would become incurable.
Hyperbole?
Unfortunately not.
Antibiotics are the bedrock of modern medicine and without them, much of the progress of the last 100 years will become undone.
Antimicrobial resistance isn’t new. The World Health Organization to the United Nations have been monitoring it and helping nations devise plans to address it. But action is not coming fast enough. The WHO estimates that antimicrobial resistance will cost an additional $1 trillion in healthcare costs by 2050, not including another $3.4 trillion in GDP losses annually by 2030.
Addressing Antibiotic Resistance
Antimicrobial resistance is a normal part of biology, as pathogens genetically change to survive. Addressing this resistance requires a multipart plan of attack. That includes hygiene control, such as hand washing and antiseptic measures in healthcare institutions. It includes vaccination to prevent illness that may require antibiotic treatment, and more importantly, the development of new antibiotics to combat evolving pathogens.
Here lies the problem. We already know that the drug development process is costly and time-consuming. Even getting penicillin from initial discovery to public access took more than a decade—and discoverer Alexander Fleming even sent the mold to anyone who asked, as he wanted to hasten its clinical use.
But we need new drugs. My own research shows that there are 39 antibiotics currently in clinical trial, including compounds to fight e-coli, respiratory tract infections, ear infections, anthrax, pneumonia, and a few others. But of these 39, five antibiotic candidates are for acne and one is for rosacea. So that leaves 33 in clinical trials to potentially treat any new bug.
Compare these 33 potentially life-saving antibiotics in clinical trials to the 429 therapeutics also in clinical trials but for breast cancer. There seems to be a disconnect.
Economic Misalignment
Economic incentives are not in place for drug discoverers to focus on this world crisis. The World Economic Forum estimates profitability for antibiotic drug development at $50 million, versus $1.15 billion for a musculoskeletal drug. Of course, pharma companies, eager to survive let alone make profits for their investors, are focused on targets with better rewards. That leaves the new antibiotic discovery to labs that are not as profit-focused, such as academic labs and smaller enterprises. However, these researchers lack the resources to carry the discoveries all the way through that pipeline.
Even if a developer creates an effective antibiotic, it will be used as the last resort for clinicians and insurance companies, who will attempt to fight the bug first with lower-cost alternatives and try to delay the development of resistance to the new drug. By the time the novel drug becomes part of mainstream treatment, it will be outside the protected patent window, and generic pricing and competition will have reduced that profit motive.
Antimicrobial resistance has been slowed in recent years due to reduced overuse of antibiotics and better hygiene practices at hospitals. But the delay of the inevitable is not enough.
Globally, we need a different economic model to incentivize researchers and manufacturers to create antibiotics for the public good. All current approaches feel like using bandaids on a gunshot wound. These include innovative models like delinkage, currently being tested in the U.K., where governments pay developers a fixed annual fee to cover R&D costs, removing volume-based sales from the equation. Other approaches include tax credits, early-stage funding, grants, and market-entry rewards to incentivize antibiotic development. In addition, there are tax credits, early push funding, grants, market entry rewards, and others.
What we need is a coordinated moonshot— in the spirit of pharma for good. The COVID crisis has shown what we can accomplish with the right priorities in place. Without that, the last century of medical innovations will be for naught and we will return to times when even a simple infection can lead to death.
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