COMING TOGETHER OF ACADEMIA & INDUSTRY

“The industry academia partnerships are important, particularly in India where we work in a highly resource constrained environment,” Dr Radha Rangarajan, Director of CDRI, Lucknow.

Dr Kallam Anji Reddy, the founder of Dr Reddy’s Laboratories, always dreamt of developing novel drugs from within India for India and the world. It remains the responsibility of the current generation to fulfil this unfinished agenda that Dr Anji Reddy wrote about in his autobiography, “An Unfinished Agenda.”

The global pharmaceutical industry benchmark is that it takes 12 to 15 years to develop a drug all the way to the market.

It is a very high attrition business, meaning that for every 100 drugs that enter phase one trials, only about 60 advance to phase 2, about 20 enter phase three and only about 12 gain FDA approval.

For every 10,000 compounds that enter the preclinical stage in the drug discovery pipeline, only one eventually makes it all the way through.

So, this is not only a very high-risk activity but also extremely expensive; figures that are thrown around go as high as $ 2 billion to take a drug to the market. 30 to 40 years ago, this figure was not so high, but in the last two decades, it has really escalated from around $ 800 million to $2 billion!

Much of this cost increase has come from the increased cost of clinical development, which includes regulatory requirements.

The industry academia partnerships are important, particularly in India where we work in a highly resource constrained environment, both spreading the risk and sharing the revenues is the only way that we can make new drugs happen

A key aspect is the availability of patients, how data is collected, how we monitor sites etc. Preclinical development is roughly 31 per cent of the total expenditure on drug R&D.

Despite all the cost and effort involved, it is mind-boggling that the number of FDA approvals between 1980 and 2020 has increased from 20-23 to about 30 in the small molecule space.

If biologics are included, the number goes around 45; we are looking at nearly $80 billion worth of expenditure in the development during this period- a roughly eight-fold increase in R&D budgets.

There is something that needs to be fixed in this model, as throwing more money at the problem is not going to solve it, and no longer enormous advances in therapeutic solutions have been made.

From the Indian perspective, in the 1990s, there was a much higher burden of communicable diseases; infectious diseases accounted for about 61 per cent of our health burden of diseases. As per 2016 data, we have about 32 per cent burden from infectious diseases and

55.4 per cent from non-communicable diseases. This is a lot like the unmet picture globally. However, India continues to carry a very big infectious disease burden, a double burden of infectious diseases and bacterial infections.

There are still a lot of TB, viral diseases, parasitic diseases and the Big Four non-communicable diseases (NCDs)- cardiovascular diseases (CVDs), cancers, chronic respiratory diseases (CRDs) and diabetes which share four behavioural risk factors –unhealthy diet, lack of physical activity, and use of tobacco and alcohol.

We may have to reckon with a mixed disease burden in the foreseeable future. So, the unmet need is quite varied within India.

And underlying all this is that whatever therapeutic solutions we deliver for this country must be affordable and accessible. There is a huge need for sustainable manufacturing.

Pharmaceutical companies in India are at the forefront of this, looking at reducing the carbon footprint in manufacturing and anticipating the changes in disease burden because of climate change.

Zoonotic diseases that were not as prevalent in colder climates may be part of a shifting pattern of infectious diseases even in the West.

The Indian pharmaceutical industry has priorities that have evolved with time, largely in the manufacture of generic drugs, including APIs and finished dosage formulations, drug delivery systems, and improved generics.

And this is how we become the pharmacy to the world, and this is how, to a large extent, we’ve contributed to lowering healthcare costs, not just in India but globally.

We also have to look at the development risk versus the innovation risk. The cutting edge in drug R&D is in therapeutic solution that address specific unmet needs and are differentiated from products already in the market and in such cases, both innovation and development risk is high.

With a few exceptions, in India out of the ten drug discovery companies that exist, most are very small startups. So, India has a large pharmaceutical industry focused on generics but a non-existent small or medi um start-up.

For that matter, there is no large In dian pharmaceutical company fo cused only on drug discovery.

Earlier, there were about 40 companies work ing with more than 200 molecules in the preclini cal pipeline in India, but the number has dwindled considerably leading to a major gap.

But this is the way drug discovery and development happens- you go from molecules to optimised lead in preclinical stage, then go to Phase 1, 2, 3 clinical developments followed by an application for a marketing approval. This is the regulatory framework that is adopted globally.

Therefore, the question remains how to make drug discovery and development sustainable in India? How can we make it repeatable? How can we take a place at the global high table for drug discovery and development?

Obviously, we need research strategies and accelerated candidate selection, which means that we need to address very specific unmet needs, we need to work on well-defined target product profiles on a mission mode.

But we need to conserve our resources and put them into very specific kinds of programmes that will take us to a common goal.

I like to give the example of the Indian space programme because it’s been hugely successful, publicly funded, at the goal and at the global forefront.

This was achieved by coming together with a set of very well-defined common goals, whether it was the Mars mission, or the moon mission, or a series of communication satellites that they wanted to launch- a very strong and unified vision.

And that sort of vision is needed in the pharmaceutical industry, in order to deliver on our unmet clinical need. It is difficult, but it can be done.

We must use more of computational technologies and AI that will drive efficiencies. And of course, we need clinical trial innovations, which, is the majority of the R&D cost.

So how can we make clinical trial innovation? How can we innovate with trial design, patient selection, site management etc.

There is a concept of patient centric clinical trials now where data collection support is provided to patients through tools that allows data to be recorded automatically and even without requiring additional interven-

We need to combine all of these things to make clinical trials more cost effective.

The industry academia partnerships are important, particularly in

India where we work in a highly resource constrained environment, both spreading the risk and sharing the revenues is the only way that we can make we can make new drugs happen.

A lot of the preclinical research is something that academic institutions and startups through partners can handle. Partnerships with academic clinical units, can be a great way to take compounds to a proof of concept in the target population.

This will de-risk the compound significantly because you will have safety and efficacy data. It is not possible for academia with its current resources to go all the way to market.

As per the European Medicines Agency’s (EMA) data from 2010 to 2019 data looking at the origin of innovation, 38 per cent of innovation in this dataset originated from large or intermediate sized companies. But 19 per cent originated from academia, public bodies, or

This is a model that has worked and, perhaps it can work much better in India. There templates that can at and many institutes in India that capable of adopting them when it comes to small molecules, biotherapeutics, pharmaceuticals, vaccines, diagnostics, medical

These existing institutions have capable scientists and the infrastructure so there is no need to start from the scratch. CDI, for example, has end to end drug discovery research capabilities, starting with computational and drug design, all the way to toxicology.

And there are a number of platform technologies for drug delivery that are available at CDRI and a fairly decent pipeline of licensing co development opportunities, which includes small molecules, fighter pharmaceuticals cost effective generics.

When it comes to solving the R&D puzzle for India, the academia can take on high risk research programs for addressing unmet clinical need.

But this should be included in close consultation with industry and collaborators from startups.

The academia can de-risk the product or the technology up to early phases of clinical development in collaboration with start-ups. This would ensure that the academic and industry partners are really in step at all stages.

The industry has to take on late stage clinical development. In this model, academia should receive a fair share of revenues or milestones, to allow for sustainable R&D cycles.

This sort of a model would allow industry and academia together to put India on the map when it comes to addressing unmet clinical needs through new drugs. And this could apply to vaccines, biologics, diagnostics, almost anything.

DR RADHA RANGARAJAN Director, CSIR-Central Drug Research Institute, Lucknow