Economic incentives for companies to develop new antimicrobials are currently too weak to support the necessary research and regulatory processes on a drug’s long and expensive journey to the clinic. Increased collaborations between governments, NGOs, pharmaceutical companies, academia, and private investors could be the vital catalyst we so desperately need.
A hard pill to swallow
Which business wants to develop a drug that the world should ideally use as little as possible?
Not many, as is becoming abundantly clear.
In terms of antimicrobials that target bacteria, in 2023, there were only 97 antibacterial agents in the clinical pipeline, according to the World Health Organization (WHO). Of these, only 32 addressed infections caused by microbes included in the 2024 WHO bacterial priority pathogen list that highlights the drug-resistant bacteria most threatening to human health. Since July 2017, regulatory agencies have approved 13 new antibiotics, only two of which represent a novel chemical class and are deemed ‘innovative.’ The recent approval of Xerava, a novel antibiotic to treat complicated intra-abdominal infections, by the Federal Agency for Medicines and Health Products in Belgium is a positive step forward, but remains a drop in the ocean as regards the threat of AMR. For AMR fungi, the list of drugs in development or nearing approval is around 10.
Read more about the threat of antimicrobial-resistant fungi here
While these scarily low numbers underscore the technical and scientific challenges in developing novel antimicrobials, sufficient financing is a major hurdle in the development of drugs that require strict antimicrobial stewardship by default. End users, such as clinicians and farmers, should use antimicrobials sparingly to limit or slow the appearance of AMR.
“These are drugs that you want to give to as few people as possible, as infrequently as possible and for the shortest time possible, so that’s not really a good business model,” explains Cédric Govaerts, director of research at FNRS, professor at Université libre de Bruxelles, and co-founder of Santero Therapeutics, a Belgian startup aiming to deliver antimicrobial drugs that use novel modes of action to target highly resistant pathogens.
A victim of early success?
AMR occurs when bacteria, viruses, fungi, and parasites no longer respond to antimicrobial drugs and is driven largely by the historic overuse of antimicrobials in the clinic or to limit infection in livestock. AMR leads to the spread of infections that are difficult, if not impossible, to treat, leading to illness and death. The problem is especially acute in low-income countries, where many people don’t have access to classic, cheap antimicrobials, let alone the novel, expensive drugs targeting AMR strains.
“The antibiotic field is a victim of early success. The initial drugs were so good that you didn’t need to improve them because they provided a real cure,” says Abel Garcia-Pino, also a professor at Université libre de Bruxelles and co-founder of Santero Therapeutics.
“Having a life-threatening situation that you can cure in one week with a drug is exceptional in the field of medicine. It’s unheard of,” adds Govaerts.
The downside to the staggering effectiveness of historic antibiotics is an unattractive economic environment for companies to begin or continue developing novel treatments. “Where is the return on investment coming from when you can sell a pill that is 100 years old?” asks Garcia-Pino. “It’s very difficult because there’s no clear business case behind the development of an antimicrobial, which makes funds very complicated to access,” says Govaerts.
Big pharma is increasingly leaving the research and innovation to small and medium enterprises (SMEs) that must grapple with the lack of investment and financing. SMEs now account for up to 81% of preclinical antibacterial pipelines.
Increased public and private investor commitments
Faced with the human and economic cost of AMR, governments worldwide are taking note. In September 2024, global leaders committed to reducing deaths associated with AMR by 10% by 2030 through catalyzing national action plans around the world. According to data from the Global AMR R&D Hub’s Dynamic Dashboard, investments in research and development of antimicrobials from public and philanthropic sources globally equate to around USD1.5 to 2 billion per year since 2017, but this decreased to under USD1 billion in 2024.
Alongside governmental and philanthropic funding initiatives, private investment is also supporting novel antimicrobials on their road to the clinic. For instance, in 2020, a large consortium of over 20 leading biopharmaceutical companies and industry associations contributed around USD1 billion to an AMR Action Fund. The fund invests in small and mid-size biotech companies developing antimicrobial therapeutics for WHO priority pathogens.
Diversified funding sources and increased partnerships will be key to achieving these goals through increasing awareness, optimizing the use of existing antimicrobials, especially in lower-income settings, and promoting research and innovation.
Continued support and investment from governments, public institutions, and private enterprise are crucial to ensure companies can begin (and hopefully survive) the antimicrobial development and commercialization process. “There are government subsidies to help companies like Santero get started. The problem is that there’s no clear path to an exit,” explains Govaerts. According to Govaerts, failure to find continued funding could at some point lead to a ‘do or die situation’ where companies don’t have sufficient investment to remain viable.
One solution could be to push new sorts of funding models, as Garcia-Pino explains: “One funding approach is called the Netflix model, where a country gets a subscription for the development of new antibiotics and then these are used only when they’re needed.” This would ensure that companies are fairly compensated for their expensive research and development while ensuring novel antimicrobials reach the clinic.
A supportive Belgian ecosystem
Brussels-based Santero now has a team of 16, funded by both private and public investors. “Almost half of our shareholders are from public institutions,” says Govaerts.
Companies outside of Belgium are impressed by this level of governmental support as it’s uncommon elsewhere. “The Belgian ecosystem has been important. When we talk with people from other countries and they realize that we’ve raised interest from both public and private investors in Belgium, they are always surprised,” highlights Garcia-Pino.
“It made a big difference being able to access that ecosystem with such a hard to fund program. I’m not sure we could have set up Santero in another country,” says Govaerts.
Belgium is due to publish a new AMR National Action Plan 2025 – 2029 this year.
