Need to fast-track new antimicrobials — Part — 1
One of the least recognized drivers of economic downturns is the reversal of public health improvements from preceding decades. This happens when preventable diseases overwhelm the already fragile and fragmented healthcare systems. The recent pandemic has proven that. Antimicrobial-resistant pathogens, bacteria, viruses, fungi, and others, pose a great threat. They have claimed 4.95 million people worldwide in 2019 alone. This is six times more than HIV/AIDS. These pathogens mutate swiftly, making new and existing antimicrobials less effective sooner.
“Anti-microbial resistance could kill us before the climate crisis does” — Sally Davies, Former Chief Medical Officer, England
This threat should not be ignored because the estimated number of AMR deaths and deaths attributable to AMR in India is higher than the global average. Factors including improper antibiotic treatment in hospitals, inadequate sanitary facilities, low incomes, and a general lack of knowledge all contribute to these alarming figures.
Current technologies and innovations
Recent studies include a wide range of approaches, from the meta-analysis of AMR’s origins in the food chain to modifying the metabolic state of AMR bacteria to develop new treatments. Research into AMR bacteria in LMICs has received much attention and effort. Antimicrobials can be used in a well-regulated manner considering dose and time, preferably after identification of the pathogen. Hence, the right diagnosis is imperative for optimal use. Innovations in existing technologies like NAATs (Nucleic Acid Amplification Technologies) and ASTs (Antimicrobial Susceptibility Testing) and the emergence of tech-enabled diagnostics like IoMT (Internet of Medical Things) are some of the latest advancements in diagnostics.
Despite their potential, these technologies are still in their nascent stages. They suffer price issues in LMICs. Antimicrobials need affordable, fast point-of-care testing. CARB-X is a world-leading non-profit organisation promoting the creation of cutting-edge products to address drug-resistant bacteria. C-CAMP is working with CARB-X as a member of their Global Accelerator Network to support early and mid-stage companies working on AMR through their mentorship and enablement programs. Two companies, Bugworks and GangaGen, supported by C-CAMP, received funding from CARB-X for their new drugs against different priority pathogens.
To combat the growing problem of infections caused by multidrug-resistant Gram-negative bacteria, Bugworks is creating a first-in-class broad-spectrum antibiotic. They are just beginning to test their principal ingredient as an intravenous and oral therapy. GangaGen is working on klebicins, novel antibacterial proteins that target multidrug-resistant K. pneumoniae, including a carbapenem-resistant strain of clinical significance. Klebicins specifically target K. pneumoniae through unique methods and should not otherwise affect the microbiome.
CARB-X is looking for entrepreneurs from around the world working to challenge the status quo of antimicrobial resistance, namely in oral therapeutics, vaccinations for neonatal sepsis, and solutions to treat gonorrhoea. These topics were carefully selected to aid LMICs and meet their antibacterial requirements.
Oral therapeutics are safe, effective and affordable. They also replace the intravenous administration of antibiotics for recently discharged patients transitioning from the hospital to an outpatient setting.
In infants, a bloodstream-related infection is called neonatal sepsis. Infant mortality due to this has historically been highest in LMICs. Gonorrhoea is one of four treatable STDs that raise HIV risk, although not enough study has been done. Even while HIV has no cure, inexpensive, quick diagnostics are available, gonorrhoea tests are costly and largely unavailable in LMICs.
CARB-X is inviting applications from startups working on oral therapeutics, vaccines for neonatal sepsis and Gonorrhoea products.
Coupling “push” and “pull” incentives
AMR is a complex problem since addressing it effectively involves close cooperation from various stakeholders, including the public. It is also a problem that needs foresight. Many global organisations and governments are promoting programs involving funding, grants, and subsidies to accelerate innovations in drug discovery and the improvement of diagnostics.
These “push” incentives urge developers to continue research on newer antimicrobials and prolong the lifespan of existing ones.
Long-term drug development, however, requires additional resources. Antibiotic discovery and development is expensive; therefore these push incentives are insufficient. To continue rewarding researchers and pharmaceutical companies for their work after a drug is market-ready, economic models of “pull” incentivization are required.
These pull incentives include market commitments, patent extensions, and delinked market entry perks (from unit sales). Recently, USA and UK adopted these ideas. GAIN (U.S. Generating Antibiotic Incentives Now) grants commercial exclusivity for life-threatening antimicrobials. The UK piloted a yearly membership scheme for manufacturers in 2019.
However, pull incentivisation may enhance antibiotic pricing for LMIC patients, adversely affecting access to life-saving antibiotics. How governments and institutions in LMICs use pull incentives to address these issues remains to be seen.
In the next part of this blog, we’ll debate broad versus targeted antimicrobial use, the need for more research on neglected diseases like gonorrhoea, and global measures to reduce antimicrobial misuse.
Additional Resource:
New CARB-X funding rounds
The new CARB-X funding call includes funding opportunities for three themes: oral therapeutics, vaccines for neonatal sepsis, and gonorrhea products. Entities can express interest in all three themes in the next two rounds with deadlines, January 30, 2023 and May 1, 2023.
For information, visit the “Apply” section of CARB-X.org, watch a 40-minute video about the funding rounds and review the FAQ page.
Fundamentals of in vitro diagnostic product development
Making the move from academic and entrepreneurial R&D to product development
To support the growth and success of the diagnostic ecosystem in India, CARB-X, C-CAMP and FIND are sponsoring a product development webinar series from Monday, November 7 through Friday, December 9. The series is for those interested in transitioning their AMR bacterial diagnostic into an IVD product.
Topics include:
11 Nov. Product development process
18 Nov. Design controls
21 Nov. Real-life stories: Academia to commercialization
2 Dec. Quality management and good laboratory practices
9 Dec. Case study: Why the fundamentals matter
Register for the series.
Resources:
- Pull Incentives for Antibacterial Drug Development: An Analysis by the Transatlantic Task Force on Antimicrobial Resistance
- The staggering death toll of drug-resistant bacteria
- https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2902724-0
- The fight against Antimicrobial Resistance is closely linked to the Sustainable Development Goals
- New Drug Approval Process in India — API FIRST
- India’s clinical-trial rules to speed up drug approvals
- Modern Tools for Rapid Diagnostics of Antimicrobial Resistance
- Antimicrobial resistance — Latest research and news | Nature
- Antimicrobial resistance
- Can financial rewards for stewardship in primary care curb antibiotic resistance? — The Lancet Infectious Diseases
- Effectiveness of Antimicrobial Stewardship Program in Long-Term Care: A Five-Year Prospective Single-Center Study
- Neonatal Sepsis — StatPearls — NCBI Bookshelf
- Sexually transmitted infections (STIs)
Disclaimer: The blog is a compilation of information on a given topic that is drawn from credible sources; however, this does not claim to be an exhaustive document on the subject. It is not intended to be prescriptive, nor does it represent the opinion of C-CAMP or its partners. The blog is intended to encourage discussion on an important topic that may be of interest to the larger community and stakeholders in associated domains.
