Biotechs do not have the arsenal of antibiotic hopefuls in their pipelines to match the growing threat of antimicrobial resistance, according to a new BIO report (PDF) published Monday.
“The breadth and novelty of the antibacterial clinical-stage pipeline is insufficient to meet the ongoing threat of wide-spread infection from drug-resistant strains,” the report concluded.
Venture funding has lagged significantly for companies working on antibiotics compared to the larger biotech industry. Co-authors David Thomas and Chad Wessel, who lead the trade group’s industry research, found that from 2016-20, venture funding for antimicrobial companies increased 29% compared to the five years prior, while funding for the biotech industry as a whole increased 175%.
For example, the study found 109 companies with assets focused in oncology raised $12 billion in the 10-year span ending 2020, compared to $700 million for just 12 biotechs working on antibacterials.
The authors say the lack of investment has created a pipeline that is not diverse enough, emblematic in the fact that only 18% of antibiotics approvals have occurred this century.
Of the 64 antibacterial treatments currently in clinical trials, more than 84% are for direct-acting novel chemical or biochemical entities. But almost two-thirds of those have targets for which there’s already a marketed drug.
Some of the drugs in development include China-based biotech Sinovent's XNW4107, which is being tested in with common antibacterials imipenem and cilastatin to treat infections from resistant bacteria. Another, Adaptive Phage Therapeutics, has a number of therapies in phase 1/2 trials for prosthetic joint infection, recurring urinary tract infection and more.
Biotech is an industry where innovation is buoyed by startups. More than 80% of the new antibiotic drugs being tested come from small companies, with large companies accounting for only eight of them. The authors worry that large pharmaceutical companies exiting the antibacterial market, coupled with a lack of licensing deals and M&A activity, has scared off investors.
Struggling antibiotics developer Entasis Therapeutics disclosed earlier this month it was fielding offers for a buyout at $1.80 per share. The share price hasn’t jumped above $4 in almost two years after the company’s IPO was priced at $15 per share.
The race for new treatments (or lack thereof) underscores the swift pace at which antibiotics are overcoming existing treatments. In a study published last month, a global team of researchers funded by the Bill and Melinda Gates Foundation and the Wellcome Trust estimated that more than 1.2 million deaths in 2019 were attributed to bacterial antimicrobial resistance. Nearly three-quarters of estimated attributable deaths were due to six pathogens, with E. coli leading mortality.
In 2020, tuberculosis was the second-highest infectious disease killer with roughly 10 million infected, behind COVID-19.
Despite the lack of investment, regulators are eager to approve new antibiotics. The authors calculated the rate of investigational new drug applications for antibiotics resulting in FDA approval was 7.9% over a 10-year span ending 2020. That's about twice the success rate compared to all other diseases reviewed by the agency. For antibacterial new chemical entities, the rate was 16.3%.
Moving forward, the report suggests that investment priorities shift across the board, from government entities to private businesses. Most importantly, the authors say incentives need to be put in place to correct a marketplace that currently does little to stimulate antibiotic innovation. The study cites the PASTEUR Act reintroduced in Congress last year as one possible solution to create a fund for subscription contracts that could be used to spur development.
“All innovation needs a functional, efficient ecosystem for it to succeed in generating life-saving products,” the authors wrote.