India needs to build antibiotic research ecosystem right away

Saransh Chaudhary, President-Global Critical Care, Venus Remedies and CEO, Venus Medicine Research Centre highlights that the preparedness and response towards AMR is also going to be a priority agenda in the upcoming G20 India Presidency. However, the government alone can only make a dent unless we, as a society, come together to rally around the rational use of antibiotics

Hitherto a blessing for humankind, antibiotics have saved millions of lives since they were first discovered almost a century ago, but these miracle drugs are losing their efficacy now due to indiscriminate use. This has led to the emergence of deadly bacterial strains that do not respond to even the most powerful antibiotics, thus creating life-threatening conditions. The situation caused by this phenomenon of antimicrobial resistance is turning so grim that we are on the brink of the pre-antibiotic era when even common infections are becoming lethally incurable.

India, where the consumption of antibiotics has increased by 2.5 times in the past two decades as a result of their over-the-counter sale, frequent outbreaks of infectious diseases and lack of infection control practices in hospitals, is the epicentre of this impending catastrophe. A recent report of the Centre for Disease Dynamics, Economics & Policy (CDDEP) has observed that in India, the isolates of gram-negative pathogen Klebsiella pneumoniae which are resistant to the carbapenem class of antibiotics have increased from 29 per cent to 72 per cent in 14 years. As per the CDDEP’s Drug Resistance Index, which combines antibiotic use and antibiotic resistance in one measure to quantify the effectiveness of antibiotics, India has fared poorly with a score of 70, indicating 70 per cent resistance and reflecting the very low effectiveness of antibiotic therapy in India.

A recent report published in The Lancet revealed that bacterial resistance was directly responsible for an estimated 1.27 million deaths globally in 2019, out of which 30 per cent were from the Indian subcontinent. There is an urgent need for new antibiotics, but economic concerns are getting in the way of developing these medicines. The problem stems from the systemic market failures that have tormented antibiotic developers over the last decade and resulted in consecutive bankruptcies. While the US and UK are incentivising the development of lifesaving antimicrobial drugs, India is still grappling with poor healthcare infrastructure and cannot afford expensive drugs as pharmaceuticals account for 43 per cent of its total out-of-pocket health expenditure. In a glaring mismatch, countries which can presumably afford the drugs do not have a large enough market, and the countries which have a large market are replete with people who cannot afford the drugs. Both instances lead to a market failure, resulting in a losing proposition for everyone.

Moreover, developing a new antibiotic is a time-consuming and costly proposition which typically takes 10–15 years and millions of dollars. The big pharma that once dominated antibiotic research has opted out because their returns from these drugs are too low to support the cost of developing them. Most companies now working on antibiotic development are SMEs, but even they are struggling to make ends meet and deliver innovative drugs. They also do not have the same bandwidth as big pharma companies to launch their drugs in large countries like India.

While the R&D focus of most pharma companies is more on lifestyle-related drugs, which unlike antibiotics can be administered for an extended period, some Indian companies have stepped in to take up antibiotic research. Going by the WHO Antibacterial Pipeline Review 2021, 10 of the 217 candidates in preclinical and three of the 80 candidates in clinical stage are being developed by Indian companies. Given that there is a significant gap between cost of development of antibiotics and its return on investment, the focus has shifted to preserving the life of existing antibiotics through either drug repurposing or the Antibiotic Resistance Breaker (ARB) approach, which offers a means to suppress the emergence of resistance and enhance the activity of existing drugs.

Bringing down the cost of antibiotic development will eventually lead to lower patient therapy cost. Developing the drug in high-income countries and selling it to underdeveloped countries like India does not make economic sense. Drug developers need to collaborate to improve access and split costs. They can reduce their expenses by conducting clinical trials in India, which has everything going for it to undertake them successfully in terms of the three Ps—population, patients and physicians. Considering that India has a population of 1.4 billion and a huge burden of infectious diseases, enrolling patients for trials is relatively easier and quicker. Considering the significant improvement in clinical research infrastructure over the last few years, the cost of conducting clinical trials will work out to be a fraction of that in Western countries. We should, therefore, encourage manufacturing of antibiotics in India, which has many FDA and EU-approved production facilities. India’s low-cost manufacturing capabilities, coupled with high quality standards, offer a big advantage.

But even new drugs can do little to tackle resistance if they are used inappropriately. Over-the-counter availability of antibiotics without prescription is a big hindrance in India and many other parts of the world. The government has woken up to this problem by coming up with National Action Plans, a Priority Pathogens list and Schedule H1 specifications to restrict availability of top-end antibiotics across the counters. Having the potential to become the world’s largest antibiotic market, India urgently needs to build an ecosystem to encourage not just innovation but also access to and sustainable use of antibiotics. The preparedness and response towards AMR is also going to be a priority agenda in the upcoming G20 India Presidency. However, the government alone can only make a dent unless we, as a society, come together to rally around the rational use of antibiotics and not take for granted the wonder drugs that enable life as we know it.