Resilience and adaptation may seem admirable attributes in humans but when exhibited by pathogens it can have disastrous consequences. When bacteria, viruses and fungi learn to resist and adapt, it leads to anti-microbial resistance or AMR or more simply, drug resistance. It is a growing menace that healthcare practitioners are grappling with on a daily basis. Studies show that in another 25 years there may be more deaths due to AMR than due to cancer or any other ailment. Dr Y K Hamied, chairman of Cipla, one of India’s leading and oldest pharma companies, has coined a new term AMMU for ‘Anti Microbial Mis Use’ to describe the AMR challenge because he sees it more of a self-inflicted problem resulting from reckless self-medication, over use and misuse. With no new antibiotics in the pipeline to replace the older ones, it has become a matter of concern.
Newer pathways
Curious and concerned minds in healthcare are consumed by the thought of what shape and form the future of medicine will take in a world grappling with challenges on multiple fronts. “The evidence is pretty clear that the bacteria and viruses are evolving and resisting the available medicines. Today, we can at best work towards prolonging the use of the available medicines by a couple of decades but then it is time to start investing in understanding newer pathways to overcome some of these older problems – Will it be in the form of nanobots running in the blood stream with research at MIT already demonstrating its feasibility,” says Nachiket Mor, economist, former banker and visiting scientist at the Banyan Academy of Leadership in mental health, who has been tracking and writing extensively on medicines and healthcare.
The ineffectiveness of medicines over time due to reckless use, he explains, is not just about complex medical problems but can happen even in medicines used to deal with common ailments like fever, cold and pain.
Apparently, the shape and form of the medicine in the years ahead will be shaped by a confluence of factors at play. Apart from drug resistance and mutating pathogens, the challenge of climate-change is complicating matters with rising temperatures triggering the spread of mosquitoes to colder regions and expanded footprint of older ailments like malaria. However, a link node running across ways to combat existing and newer ailments is the transformation in medicines possible with technological advancements. For example, artificial intelligence-based risk-profiling to ensuring automated infusion of insulin through a pager-sized device that can act like artificial pancreas or genomics-guided diagnosis and genetic-makeup-led precision cancer treatment do not fall within the realms of fictional future anymore. This, even as researchers are showcasing the path ahead with newer possibilities including nanobots running in the blood stream to fix ailments, gene-edited humans backed by robotics and machine-guided treatments and interventions at the DNA level.
Mixture for miracles
Dr V Mohan, a leading diabetologist and the co-founder of the eponymous chain of diabetes specialities centres around the country, feels the transformations unfolding in world of medicines “have both a good and a worrying side to it. The good part is that technology is now enabling absolute miracles to occur like for instance, a pager-sized device can today act like an artificial pancreas ensuring automated insulin delivery and simplifying the life of a highly diabetic person. But then, the worrying side is the high cost of newer therapies that put many of medications beyond the reach of the common man. For instance, Ozempic or Wegovy drugs for diabetic patients, more popularly known as weight-loss drugs.” It is today priced at around $ 1000 a month in the US. According to sources in Novo Nordisk in India, Wegovy, which is likely to be launched in India by the company, the date of launch and the price is yet unknown. But then, the pricing may not be on par with the US market but curated more to suit the Indian market and thereby expand the reach of the drug in India.
However, if it is not new medicines that are under patent, then Dr Mohan feels, Indian companies have displayed a commendable track record in flooding the market with low-cost generics.
Cost & cure
Convinced that India could also win the cost war in this evolving shape and form of medicine, Vijay Chandru, co-founder and director, Strand Life Sciences and CRISPRBITS, who has spent 25 years studying and leveraging genomics for medical diagnostics and a strong believer in genomic sequencing following an exponential law that is even faster than Moore’s law of information technology has this to say on the cost component: “to get a sense of this trend we should note that just over 20 years ago, the cost of sequencing was roughly at 1 Million USD per gbase or gigabase (a string of I billion nucleic acid / a unit to measure the length of DNA) of nucleic data. Today, we are staring at 1USD per gbase. India is well positioned to leverage the million-fold reduction which heralds a new era of democratization of genomics. A high quality (deep – 80 to 120x – copies of DNA) whole exome sequence (all 20,000 genes) is already possible at under 10,000 INR.” He says, “if as a society, if we are to correct misalignments (in our health and insurance systems) to truly value preventive care and early detection at primary care, genomics-guided diagnostics should lead the way towards universal health care.”
Gene-editing – hubris, hurt & hope
Undeterred by the setback suffered by hurting startups in the gene-editing therapy space, Chandru, says, points to the much celebrated Gartner hype cycles and says, “the AI Winter (trough of disillusionment) started in mid-80s and the plateau of productivity came in 2009. In Bioinformatics, the trough of disillusionment came in 2003 and the plateau of productivity came 10 year later in 2013.
With the marketing machine that the world has been dominated by – every technology breakthrough goes through the Gartner Hype Cycle.” He then goes on to quote US-based physician-scientist Rene Mora, also described as an investor, banker and consultant, as saying: “we are in the third stage of the Gartner Hype Cycle (trough of disillusionment) when it comes to CRISPR technologies. Recovery to the next phase will rely on continued improvements in technology and most, importantly, finding the best applications.”
Since therapeutics is a long gestation play, Chandru advocates and has adopted the approach of taking a parallel revenue stream through diagnostics products and gene-editing services play, which apparently also gets to be an attractive proposition for private equity.
CAR-T & beyond
To him, the prospect of edited humans is not a fictional future but an inevitable reality with right ethical guard rails to ensure use for curative purposes only. He explains: “Let us discuss CAR-T (chimeric antigen receptor – T Cell) cell therapy, the fabulous immunotherapy for liquid cancers (like blood cancer), that has been seen as the cutting edge of cancer care. Within 8 years of the first approval Kymriah in 2017, we have two therapies in India approved and offered by ImmunoACT (result of a collaboration between Dr Rahul Purwar from IIT Bombay and Tata Memorial Hospital) and Immuneel (from a company backed by Biocon founder Kiran Mazumdar-Shaw and oncologist Siddhartha Mukherjee) at just around 50,000 USD which would be around 5-10 per cent of the comparable costs in the so-called innovator markets. The biotechnology and infrastructure requirements to go from CAR-T to gene therapy and on to gene-editing is just a hop, skip and jump away figuratively. Several teams in India are at it.”
He however reminds that “the third global-observatory on the ethics and social impact of gene-editing will be discussed at the American Academy of Arts and Sciences in Cambridge, Massachusetts in May 2025 and India will be well represented at the meeting.”
Stage of cancer does not matter
On cancer-care and the transformation in the approach to medicines, Dr B S Ajaikumar, a leading oncologist, founder and executive chairman, HealthCare Global Enterprises (HCG), “oncology is a constantly evolving space with changes happening every two to three months with new mutations and newer understanding.” This space has evolved significantly over the past five to 10 years, he says. “Earlier, drugs were given based on randomised trials. Now, the advances have been made in understanding the cancer cell in a particular individual and therefore focus is on designing a much more focussed therapy and personalised care. For example, there is targeted drug with chemotherapy – the antibody drug conjugate and newer drugs in this category- to make treatment precise and personalised.” Since each individual is different needing customised care, he says, “it is no more a broadly defined breast cancer or lung cancer but much more specific. Also, the stage of cancer, he says, “is no more a yardstick and does not matter really as people with stage four have also lived for many years.”