Antimicrobial resistance (AMR) has been categorized by the World Health Organization (WHO) as one of the top 10 health threats worldwide. The U.S. Centers for Disease Control and Prevention report that approximately 2.8 million people in the United States develop an antibiotic-resistant infection each year, resulting in more than 35,000 deaths annually, while the WHO estimates that roughly 700,000 people die from drug-resistant diseases globally each year. Despite the severity of the need, however, the pipeline for new antibiotics is thin and dwindling.
There are multiple factors that have led to this state of affairs regarding AMR, including the overuse/misuse of antibiotics and the natural evolution of bacteria. Similarly, the anemic pipeline of antibiotic candidates is also due to a variety of issues, chief among them the sheer cost of bringing a compound from early development to commercialization.
It is that very issue that the AMR Action Fund hopes to address.
The AMR Action Fund is an expansive effort to not only breathe new life into the antibiotics development field, but hopefully kickstart momentum to encourage ongoing R&D. This initiative unites pharmaceutical partners and global health organizations, with members such as the WHO, the European Investment Bank and the Wellcome Trust. As of July, 23 pharmaceutical companies had signed on to the Fund as investors, including industry giants such as Roche, Pfizer, GlaxoSmithKline, Amgen, Merck, Novartis and many others. The fund intends to invest more than $1 billion to advance promising candidates, with the aim of having two to four new antibiotics to market by 2030.
Greg Frank, an infectious disease scholar and policy expert at BIO, and Martin Bott, Eli Lilly’s vice president of finance and interim general manager of the AMR Action Fund, recently held a virtual fireside chat during the 2020 BIO Investor Forum to discuss the Fund and its plan of attack.
“The CDC has a list of 16 antimicrobial resistant threats, and if you just take eight of them, those threats represent almost $6 billion in annual direct healthcare costs in the United States,” Frank said in the fireside chat. “And globally, AMR represents almost 700,000 deaths in the here and now. There have been estimates as to what happens if we do nothing. In the United Kingdom, a group estimated that if no action is taken to intervene in this issue, by 2050, there will be 10 million lives lost annually—which is higher than the death toll for cancer.”
The chief challenge in encouraging the development of more antibiotics, he noted, is that they are considered a commodity, which Frank likened to fire extinguishers—valued only when you really need them. Low demand drives a low price, leaving companies unable to recoup their development costs, let alone turn a profit.
Bott summed up the problem succinctly: “Lack of innovation due to lack of valuation.”
That’s where the Fund will come in, to provide funding to promising candidates. Silas Holland, interim head of External Affairs for the AMR Action Fund, explained that the Fund “will make investments in biotechs developing high-priority antibiotics through equity or debt instruments.”
According to Bott, the goal is to have the Fund operational by the end of 2020, and work is underway to establish a management team, board of directors, an independent scientific advisory board and the necessary legal documents, “so that the management team can really start assessing investment opportunities as early as the first quarter in 2021 and make those investments.”
“Obviously there is need on many fronts, and the fund has to focus in certain areas, and unfortunately will not please everybody because they may be outside the scope. The main focus will be on the science. We really have to make significant progress in the battle against these priority pathogens. We don’t care if it’s a small molecule or a large molecule or the modality; everything is game as long as it addresses infections caused by these pathogens,” he said, though he did note that there will be a focus on Phase 2-ready candidates.
Bott noted that they consider the AMR Action Fund to be “an engaged owner fund,” explaining that in addition to financial support, “the fund will have a capabilities team to assist, advise, consult portfolio companies, augment their capabilities in topics like clinical trial design, regulatory strategy, CMC manufacturing type work, and so forth. The goal is really to make sure we don’t lose time, that we progress promising science as rapidly as we can, but also in a quality fashion and with a global market in place.”
“To be very clear, this is only a temporary solution; it’s another ability to provide some financing, etc. [But] if we do not fix the right pull incentives, the right market rewards for this, we might have done something good in the near-term, but we have to fix it more sustainably, so that there would be a constant flow of innovation as we experience in so many other therapeutic areas with tremendous benefits for humankind,” he insisted.
The hope, according to the AMR Action Fund’s website, is that this temporary solution will get enough antibiotic candidates to the market to “provid[e] governments time to make the necessary policy reforms to enable a sustainable antibiotic pipeline.”
“Even if you use an antibiotic perfectly whenever it was needed, that in itself would still drive resistance. So you can’t out-steward your way out of this problem. We have to have that steady pipeline of new medicines coming to the market and patients that always keep pace with resistance. Resistance is never going to go away; this is a never-ending evolutionary arms race,” said Frank.