Even though medicines can now be built for a single patient, our drug rules require them to be tested as if they are going to be administered to millions. Many countries allow physicians to act on their clinical judgement where options are limited. India has more reason than any other country to adopt the same approach.
Earlier this month, the New York Times carried a widely forwarded essay about Annette Harlow, a woman in her eighties who, in early 2020, had been told that her lung cancer had stopped responding to treatment. Soon after that, she was enrolled on a Phase 1 trial of a new drug, and six years later, she is still alive. As heartening as the story is, the larger point it makes is that it is not science which holds us back today — but the failings of our regulatory system.
Medicines for One, Rules for Millions
According to the article, the number of new drugs approved per billion dollars spent on research has roughly halved every 9 years since the 1950s (what researchers refer to as Eroom’s Law — Moore’s Law spelt backwards). For the most part, this is because of how hard it is to get drugs approved. Two of the insulin products for which Novo Nordisk had sought approvals had documentation so extensive that, if printed, the pile of paper would have been taller than the Empire State Building.
Given that drugs can now be designed for the specific requirements of individual patients, our current approach seems even more out of place. Six years ago, I made a podcast episode about a couple who built a laboratory in a bungalow in Bangalore to find a treatment for the rare disease that was killing their son. Things have evolved rapidly since then. Last year, a base-editing therapy was designed, manufactured and administered to an infant with fatal genetic disorders within months of his birth. As recently as last week, a new gene therapy was announced that could help treat leukaemia by getting the patient’s own liver to manufacture the required therapeutic protein.
Our regulations were designed for medicines manufactured en masse for use on millions of patients. They are, as a result, singularly incapable of doing what is required to test a medicine that has been custom-built for use by a single individual.
The Healing Attempt
Recognising this, some countries have already begun to apply different standards. Australia no longer requires its regulator to review a new therapy before it is tested in humans, leaving the question of whether it is safe or not to a hospital ethics committee. Germany has adopted a doctrine it calls Heilversuch (the healing attempt), under which physicians can, with the patient’s informed consent, use their own clinical judgement to try new therapies to treat their patients. It was this approach that allowed a thirteen-year-old American girl, for whom American scientists had designed a personalised cancer vaccine, to be treated in Germany in the short time she had left, after she was forced to fly there to receive it. What is possible in Germany within days would have taken months at home.
In many ways, all that is wrong with the American system is worse in the Indian context. We not only copied their rulebook, we also added impediments of our own to it. Because our New Drugs and Clinical Trials Rules of 2019 treat every gene therapy as a new drug, the guidelines under them stipulate that it needs to clear four committees before it can reach a patient. A CAR-T therapy for a handful of patients is held to the same standards as a drug aimed for use population-wide. Even compassionate use of unapproved drugs for patients with life-threatening diseases requires the regulator to say yes in each individual case — a process that is often unnecessarily cumbersome.
Last year, I argued in this column that the gene therapy guidelines issued by the Indian Council of Medical Research offered us a pathway out of the bind we found ourselves in. India’s first CAR-T therapy and its first CRISPR treatment for sickle cell disease managed to use this pathway to see the light of day. But having seen what Germany and Australia are doing, I no longer believe this is enough. If we want to take advantage of all that modern technologies have to offer, we need to be far more courageous than we currently are.
New Approach to Treatment
We have more reason to do so than anyone else. India has the largest number of endogamous communities in the world. Within them, the same rare mutation recurs across the community, as a result of which, a therapy designed for one can be used to treat dozens more. No Western country has a comparable demographic. Which is why we, more than anyone else, have such a strong incentive to find cures that work faster and more cheaply.
The National Policy for Rare Diseases has designated 16 centres of excellence and offers up to 50 lakh rupees for the treatment of each patient. Even so, last October, the Delhi High Court had to instruct the government to properly fund the programme, having found that crores of allocated funds had lain unspent for years.
What those centres lack is not funds but permission. Absent a radical change in our approach to treatment, we will fall short of the objectives we have set ourselves. Physicians need to be allowed to treat their patients (always with their consent, of course) based on their own clinical judgement and without waiting for regulatory approvals. They should do so on the condition that each attempt is monitored and all the lessons learned, are properly pooled so that each patient who has been treated successfully becomes evidence for the next.
What the family I featured in my podcast six years ago did alone and unaided is what our centres of excellence should be doing for all families like theirs. The science is here. What we need is the freedom to use it as extensively as possible.