A new report examining the antibiotics landscape in the US has highlighted the need for public policy solutions as investments in the sector wane and large drugmakers abandon the space.
The report, ‘The State of Innovation in Antibacterial Therapeutics’, published by the Biotechnology Innovation Organization (BIO) this week, emphasises the need for improved innovation in the antibiotics sector. According to the report, the most crucial policy reforms are those that address the beleaguered antibiotics marketplace.
The current antibacterial pipeline is inadequate to tackle the threat of drug-resistant infections, and antibiotic discovery must be broadened to address new targets, according to the report’s authors. Of the 72 antibacterial drug programmes currently underway, more than 38% target C. difficile and tuberculosis, leaving just 44 drugs indicated for other disease-causing bacteria.
Many antibiotics already on the market will become less effective due to antimicrobial resistance (AMR), the report says, and there must be a “well-funded and appropriately rewarded biotech ecosystem” to enable the development of new antibacterial drugs to fill the gap.
In addition to a diminishing pipeline of new antibiotics, approvals have slowed in recent decades; over 82% of all FDA-approved antibiotics were authorised before 2000. The report’s authors also note that in the last 35 years, just one antibiotic with a new molecular target or novel mechanism of action has been approved by the regulator.
BIO president and CEO Dr Michelle McMurry-Heath said: “Over 1 million people worldwide lost their lives to drug-resistant bacteria in 2019. We urgently need new, effective antimicrobial medicines to keep up with ever-growing resistance.”
It’s not all bad, though. In contrast to the report’s largely bleak findings, BIO calculated the overall success rate of antibacterial new chemical entities (NCEs) – from Phase I to FDA approval – to be 16.3%, significantly higher than the industry average of 7.9%.
As the number of new antibiotics reaching the market has declined over recent years, so too have the investments in the space. Over the past decade, US antibacterial-focused companies received $1.6bn of venture capital funding, compared to the whopping $26.5bn channelled into oncology.
In the last 10 ten years, while initial public offerings (IPOs) for 12 US antibiotic biopharmas totalled just $700m, 109 US oncology companies raised $12bn – meaning antibiotic ventures received almost 17 times less funding than cancer-focused companies.
BIO says the $2.3bn raised by antibiotic-focused start-ups over the last decade, through both venture capital and IPOs, is not enough to compensate for the broader ecosystem and diverse pipeline candidates that the sector needs.
The organisation offers three main reasons why investors have avoided antibacterial development: the majority of biotechs receiving FDA marketing approval have ended up as commercial failures; there is a lack of policy and regulatory solutions that address the challenges of the antibiotics marketplace; and large, leading drug companies have been exiting the space for years.
Need for policy solutions
The report proposes a number of steps that can be made to increase investment and innovation in the antibiotics sector. The solutions, the report says, are interconnected and dependent on each other.
Firstly, there must be early-stage investment and incentives in antibiotic research by governments, philanthropic foundations and institutes. The creative hybrid models of funding can encourage the early development of promising new drugs – global non-profit partnership CARB-X, for example, provided $360m in funding across 92 projects in 12 countries over a five-year period.
There must also be late-stage investments to support small companies with promising candidates as they enter expensive and complex Phase II and III trials. The report cites the US Biomedical Advanced Research and Development Authority’s Project BioShield and Broad Spectrum Antimicrobials programmes as examples of public-private partnerships that can help accelerate the late-stage research and development of investigational products.
Regulatory measures that address key challenges, such as trial enrolment and running large, complex comparative effectiveness studies, must be introduced to minimise the obstacles faced by antibiotic drug developers.
The bipartisan Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act, a policy proposal currently under consideration by Congress, seeks to establish a subscription model under which drugmakers would be paid annual, agreed-upon amounts depending on the clinical need and novelty of their drug.
To address the unique challenges of the antibiotics market, there must be “a pull incentive to ensure sustainable investment into the AMR product pipeline, and reimbursement reform to stabilise the commercial marketplace and improve patient access”. The report says one solution is to have separate payments for antimicrobial drugs under in-hospital Medicare reimbursement. The move would ensure that hospitals are adequately reimbursed for these drugs, and the necessary antimicrobial is prescribed “based on clinical, not financial, considerations”. Reimbursement reforms such as this would secure patients’ access to novel antibiotics when appropriate, and address the poor market appeal of AMR drugs, the report says.
David Thomas, vice president for industry research at BIO and one of the report’s authors, said: “Robust innovation in this space is absolutely critical to tackle the global threat of antimicrobial resistance, and we believe public policy solutions are necessary to realign market incentives and encourage more innovation.”
Big pharma’s exodus
With just four major drugmakers remaining in the space, antibiotic research has been effectively abandoned by large pharmaceutical companies. Pharma giants Novartis, Sanofi and AstraZeneca all announced their departure from the sector in recent years, choosing instead to focus their efforts on more lucrative areas of research.
Of the antibacterial candidates currently under development, 80% originate from small, emerging biotech companies. BIO’s report has warned that as funding for these drugmakers wanes, the sector stands to lose the companies driving the much-needed innovation in the space.
According to BIO, 12 antibiotics companies went public in the past decade – and just five remain active today. Large pharma companies were traditionally critical to the antibiotic ecosystem, the report says, offering “extensive manufacturing infrastructure and global distribution capacity”.
While the small companies leading antibacterial drug discovery and development sector offer the promise of new novel antibiotic candidates, big pharma’s exodus from the field leaves its future uncertain.