Why India should support antibiotic development

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India needs an investment mindset that can fund and support drug discovery and development

India needs an investment mindset that can fund and support drug discovery and development

Antimicrobial resistance (AMR) is a looming public health crisis affecting every country in the world with a disproportionate impact on lives and livelihoods in low- and middle-income countries. A recent report by the Global Research on AntiMicrobial resistance (GRAM) project found that in 2019, approximately 4.95 million people suffered from at least one drug-resistant infection and that AMR directly caused 1.27 million deaths. .

Antimicrobial resistance is one of India’s major public health problems, directly contributing to about 30% of neonatal sepsis deaths in India. These are due to multidrug-resistant nosocomial infections (MDR) in many cases. Over 30% of COVID-19 deaths in India could be attributed to our inability to treat secondary bacterial infections caused by MDR pathogens with the appropriate antibiotics.

The irrational use of antibiotics by the medical community, the general public, and farmers is generating drug-resistant superbugs. Inadequate infection control measures in hospitals and poor sanitation in the community lead to the spread of these superbugs. Currently, there is no reliable and rapid point-of-care diagnostic that can guide the clinician in the choice of antibiotic to use. and spare blind use when not needed.

To tackle the antimicrobial resistance crisis, we need strong investments in research and development of new antibiotics, rapid and affordable diagnostics, strengthened infection control and prevention practices, formulation and implementing antibiotic stewardship programs across the country and ensuring equitable access to life-saving antibiotics. Moreover, curbing the growing trends of antimicrobial use in various sectors requires an integrated One Health approach that focuses on all four spheres: humans, animals, food and the environment. One such immediate response is the welcome move by the Indian government to pass legislation banning the use of streptomycin and tetracycline in agriculture and the growth-promoting use of colistin in poultry farming.

With India’s reputation as the pharmacy of the Global South, with many compliant global manufacturing plants, it is time to expand our focus and investment in early R&D of life-saving antibiotics. We have the essential intellectual firepower and talent pool. However, we need strong government and private sector investment in specialty training coupled with an investment mindset that can fund and sustain drug discovery and development.

Pipeline of dry antibiotics

Over the past decade, the success rate from Phase 1 to FDA approval for new antibacterial drugs has been found to be 16.3% compared to the overall industry average of 7, 9%. Despite this higher success rate, antibiotic development suffers from a lack of investment and rapid market adoption of newly approved products. Several companies that have successfully moved new antibiotics from discovery to approval have filed for bankruptcy due to market dynamics. The exit of big pharma from antibiotic development, coupled with a lack of investment from venture capitalists and the paucity of enabling regulatory and policy solutions to support the commercial viability of antibacterial agents, has pushed the antimicrobial resistance in a global health crisis.

While no one questions the unmet need for antibiotics, a comparison of COVID-19 and oncology drugs provides a stark example of how the clinical pipeline for new antibiotics is out of balance. In 2020-21, there were 260 COVID-19 antivirals in clinical development, and for drugs intended to treat breast cancer alone, the number was 158. In contrast, the number of new antibacterial agents in clinical development was at a number.

Why is the antibiotic market broken and the drug pipeline ultra-thin? Unlike most new drugs, after approval, new antibiotics are used sparingly (antibiotic stewardship practices) and reserved primarily for cases where older antibiotics are ineffective. This strategy is essential to preserve the longevity of a new antibacterial agent and delay the emergence of drug-resistant bacteria. Additionally, reimbursement mechanisms in several countries discourage hospitals from using an expensive new broad-spectrum antibacterial agent when a cheaper generic option is available. These unique challenges in current treatment guidelines and archaic reimbursement models contribute to commercial failure and restricted or lack of access for patients who urgently need these lifesaving agents.

Most of the big pharma companies have left the AMR space due to low return on investment (ROI). Surprisingly, around 80% of antibiotics currently in the clinical pipeline are developed by small biotech companies.

To reverse this trend, we need immediate solutions and long-term sustainable mechanisms.

The push-pull model

Small companies are getting seed funding from public-private partnerships like CARB-X (Lutting Antibiotic Resistance Bacteria Biopharmaceutical Accelerator), which has provided more than $360 million in funding for 92 antibacterial projects over the past five years. This funding is an example of the push model that has catalyzed the creation of a strong pipeline of early discovery stage projects.

The vector of attraction may come from the PASTEUR law (Pioneering Antimicrobial Subscriptions to End Upsurging Resistance), if and when the US government adopts it. This law will encourage antibiotic developers with substantial upfront funding for new antibiotics that will gain regulatory approval. Companies that develop much-needed antibiotics for drug-resistant infections would receive a federal government contract ranging from $750 million to $3 billion over ten years.

To encourage the creation of new treatments, the US Congress enacted the Generating Antibiotic Incentives Now Act (GAIN Act) of 2012, which provides benefits to qualified infectious disease product (QIDP) manufacturers, including five years of additional exclusivity without a patent. However, the inclusion of molecules regardless of the potential for treating drug-resistant infections diluted the benefits of the GAIN Act.

Another promising initiative is to decouple the value of antibiotics from the volume of sales. The UK is about to launch the world’s first ‘subscription’ system for antibiotics. This initiative will pay manufacturers of anti-infectives a flat rate for making new drugs available to the National Health Services (NHS). This is a guaranteed regimen regardless of how much or how little these new drugs are used in treatment.

In addition, the recent creation of the AMR Action Fund, whose mandate is to invest more than $1 billion to fill current funding gaps in the development of new antibiotics, will give a boost to molecules in phase advanced clinical development.

( Abdul Ghafur is the Coordinator of the Chennai Declaration on Antimicrobial Resistance and Consultant in Infectious Diseases at Apollo Cancer Institute, Chennai.)

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