I write in The Hindu on what it takes to get a drug from the lab to the market. Here is the full piece along with hyperlinked references.
January marked an important breakthrough in the fight against tropical diseases. Researchers at the International Centre for Genetic Engineering and Biotechnology (ICGEB) in Delhi found a drug candidate that prevented the TB and Malaria pathogens from infecting human blood cells.
This cutting edge research took place not just in India, but for Indian challenges — whose solutions have global implications. Further, Anand Ranganathan and his colleagues did not just find this drug candidate, but also helped develop processes to develop these drug leads. It also happened thanks to a combination of a UN facility set up decades ago, attracting top global research talent to come back to India and work here. And the research was funded not just through international sources, but also a ‘Grand Challenge Programme’ on vaccines set up by the Department of Biotechnology, Government of India. Much of this success is a delayed fruit of a biotechnology push in India that started in the mid 1980s, which has gained in strength over time.
However, the discovery of the drug candidate ‘M5 synthetic peptide’ is the beginning of a long road and not the end. The process of drug discovery here is not yet complete, and has to be succeeded by more research and a host of clinical trials. Here is a plausible set of intermediate steps before a new TB or Malaria drug enters the market from the work of Ranganathan and others.
The ICGEB researchers have attempted ‘rational drug design’, where they have not only found a drug candidate, but have done so while identifying what protein target it interacts with in the body, and the mechanism it uses to prevent disease. The first steps forward for all interested researchers in the field will likely be to study further how the peptide drug candidate works, what its structure is, what the key biochemical interactions are, and how its target proteins behave.
While the drug candidate might work well in a test tube or an agar plate, its efficacy in the human body is an entirely different story. At this stage, whether the peptide can be easily absorbed by the body or be happy in blood, whether it finds the right targets, has no side effects or toxicity, are all unknown. Researchers, including those in private pharmaceuticals, can start developing variants of the M5 peptide that might have more desirable properties and have higher efficacy, and a good number of promising drug candidates might be patented by public sector researchers or pharmaceutical companies, depending on who discovers their utility.
It is after this that pre-clinical trials start on promising compounds, from tests in mammals to finally humans. Phase I clinical trials are typically about testing safety among healthy people, moving to phase II which are small trials of efficacy among patients. The last and the most expensive — Phase III, involves large, double-blind tests to determine both safety and efficacy among large groups of people.
The entire process of drug development is one of attrition, where a hundred lead compounds might trickle down to one or two medicines. It can take a decade or more, and cost in the order of a billion dollars, or 6000+ crore rupees.
Science is often described in popular retelling in a triumphalist manner, when in reality research involves many misses by researchers, incremental progress, and the eventual success of someone who stands on the shoulders of many giants.
For this process to happen, you need to have a robust research ecosystem, adequate funding, and good pipelines that ensure minimum friction in the development of drug candidates and lead compounds into medicine that you can buy at the corner shop.
The challenge in India is that tropical diseases have often been neglected by big pharmaceuticals because the size of the drug market is lower, with people having lower incomes in tropical countries. Further, companies are uncertain about intellectual property rights on essential drugs, unsure about whether they can recover high sunk costs in this inherently risky proposition. It is no surprise that big Indian corporations have stayed away from pharmaceutical R&D, finding more secure avenues for a return on their investment.
Policymakers in India will need to strike the right balance between public funding, and the role and return on private investment on drug development. Greater clarity on India’s eminent domain and compulsory licensing positions could make foreign-patented drugs more costly for India, but might spur R&D on tropical and endemic diseases in the long run.
Further, the unwritten compact in developed countries on drug development is that a thick layer of public funds pay for the basic research up to and including drug candidate discovery. It is over and above this that private pharmaceuticals come in, patent drugs and develop them.
Indian funding on basic research and drug discovery remains minuscule in comparison, with the entire Department of Biotechnology budget being lesser than 1500 crore rupees in 2014-15, or about 250 million dollars. The Government of India’s spending on drug development is broadly of the same order of magnitude of what is spent by the Gates Foundation and others on drugs for tropical diseases, and both the quality and quantity of public spending has to dramatically improve if we want more drug candidates against TB, Malaria, Dengue, Cholera and other diseases.
One way to increase the funding is to redirect extensive funds that go towards large healthcare subsidies, so that future drugs can be both better and cheaper.
India also has the opportunity to re-examine how clinical trials are governed. While we want ethical and safe practices in clinical testing, American or European regulations have accumulated some extra bureaucracy and regulations along the way. India can also set new standards on transparency so that new research is easy to discover, verify and build on.
Getting 21st century medical solutions to India’s health concerns is a long slog. The new potential cure for TB and malaria gives us a chance to think through how to develop medicines in India, and for India.
Read the article in The Hindu on their website.