Pressing need for new antibiotic research reimbursement models

Antibiotics can destroy bacteria or inhibit their growth to cure deadly infections, but their irrational use has led to a bacterial backlash with the microbes developing resistance against them. Called “superbugs,” these dangerous bacterial strains are causing infections for which no cure is in sight. Even powerful antibiotics have been rendered ineffective against them. An increase in the frequency of antimicrobial resistance (AMR), as the phenomenon is called, has been observed for all major classes of antibiotics.

The problem has particularly reached alarming proportions in India, where the consumption of antibiotics has gone up by a staggering 150 per cent in the past two decades. We should deal with this crisis on a war footing by creating awareness about the judicious use of antibiotics, ensuring adherence to infection control practices in all hospitals and implementing antibiotic stewardship programmes across the country. At the same time, the role of antibiotic research and development in stemming the tide of resistant bacteria cannot be overstated.

Research on antibiotics is not a profitable proposition owing to their short duration of use, longer research span and high R&D costs. However, more than the cost of research, it is the counter-intuitive and unique nature of how antibiotic companies make money that is driving large companies away from antibiotic R&D. Take, for instance, the case of cancer. When a new breakthrough therapy for cancer is approved, the drug is almost immediately brought to use for target indications. This is not the case with antibiotics. In fact, there is a disincentive for freely using a novel antibiotic drug because of the risk of it developing resistance. As a result, all drugs that target hard-to-treat infections and priority pathogens are immediately classified as “reserve” drugs, and are only used in rare circumstances when no other treatment option is available. While this is critical for antibiotic stewardship and prolongs the useful life of the drug, it is a significant disincentive for companies investing in antibiotic research as it is counterproductive to how companies recoup their investment.

This problem has been recognised by many governments around the world, and the most viable solution proposed to solve it is to delink antibiotic sales from Return On Investment (ROI). This can be achieved in various ways. However, the most widely accepted solution is that of a de-linked subscription model where antibiotic developers are reimbursed a fixed amount each year for keeping the drug in the market irrespective of sales. This approach has been described by Kevin Outterson, a global thought leader on business models for antibiotic development and use, as the ‘fire extinguisher’ strategy wherein governments pay to have a potent drug in the antibiotic arsenal, akin to fire extinguisher, in case a drug-resistant life-threatening infection (i.e. fire) needs to be treated. The UK became the first country to roll out such a strategy last year when it approved two antibiotic drugs under the National Health Service (NHS) subscription pilot.

India needs to seriously consider an equivalent strategy to ensure consistent access to novel antibiotic drugs and support an antibiotic research ecosystem in the country. As it is, most of the antibiotics in the clinical pipeline in India are being developed by small biotech companies, many of which have gone bankrupt despite having successfully cleared the dreaded FDA-approval stage.

No new class of antibiotics has been developed since 1987 because developing it takes a lot of time, effort and funds with still no success guaranteed. Developing antibiotics to combat highly drug-resistant bacterial infections is even more challenging. Therefore, the focus has shifted to developing innovative solutions by enhancing the efficacy and shelf life of the existing antibiotics through novel technologies. These include approaches like Antibiotic Resistance Breakers (ARBs), also referred to as antibiotic adjuvants. Non-antibiotic moieties, which, in combination with antibiotics, enhance their efficacy and help overcome resistance barriers, ARBs offer an alternative to new antibiotic discovery.

Beta-lactamase inhibitors, for instance, have given a new lease of life to so many of the most-widely consumed critical care antibiotics, like piperacillin-tazobactam where piperacillin is the antibiotic and tazobactam is a beta-lactamase inhibitor, or an ARB, which restores the efficacy of piperacillin.

The current global antibiotic pipeline is dominated by research on other types of beta-lactamase inhibitors that all work as ARBs to restore the efficacy of the main antibiotic compound. More recently, alternative approaches like bacteriophage therapies and other non-traditional therapies are also being tested in clinical trials to tackle specific types of resistance.

Despite the potential of these technologies, the enormous challenges involved in monetising them is a big limitation. Hence, there is a dire need to create a viable antibiotic research ecosystem, and this can only be achieved through government intervention. Let’s all gear up for this war against AMR. We just cannot afford to lose it.