‘India may get its first novel drug by 2014’

From the last few years, almost every Indian company worth its name is talking of having novel molecules — new chemicals entities (NCEs) and a few new biological entities (NBEs) — in its kitty. But the process to discover and develop and to bring to market a novel medicine is fraught with huge risks of failure, costs, etc.

At the DNA Conversations forum, pharma sector experts — Neelima Joshi, vice-president, biological research, Glenmark Pharma, Raj Kamboj, president, novel drug discovery & development, Lupin, S M Sapatnekar, dean, Clinical Research Education & Management Academy (Crema) and Hitesh Sharma, partner & national leader, health sciences practice, Ernst &Young — discussed the risks and rewards of pharma R&D. DNA moderated the discussion. Excerpts:
 
With so many NCEs, is it a deliberate attempt by the Indian pharma to wash away the ‘generics only’ tag?

Joshi: When a company decides to go in for innovation, it’s a huge commitment, both scientific and financial. There is a big regulatory component involved. It needs clinical development expertise. It’s a big commitment in terms of developing infrastructure, hiring talent and developing expertise, which is cost intensive. And second commitment is financial. Bringing a new drug from the lab to the market costs a phenomenal $1 billion and it may reach $2 billion shortly. We have a very rich clinical pipeline, with dozens of compounds in phase I trials, double the number in phase II and a few compounds in advanced phase III trials.

Kamboj: It’s not by choice that all key pharma companies in India or globally can’t just rely on generics or branded generics. They have to advance to the high value chain—NCE/NBEs. Cost advantage of India will help. Intellectual property behind it gives a boost. To become a global player, Indian pharma has to do it.

Sapatnekar: Six months back AstraZeneca did not have anything in its pipeline after 2009. Companies can’t run like this. It acquired another company. This is a juggernaut. You can’t simply say I don’t have molecules, buy them, but the juggernaut has to go on.

Sharma: In order to get to the next level, you have to meet this particular level. Industry recognises that it’s a high risk, high reward game. Although no successful molecule has reached commercialisation stage, but at various stages companies have encashed on value. That itself is a good kind of indicator for the industry. I think in the regulated markets, there are a lot of processes which drive research in a particular way. That’s another area where Indian scientists are trying to see if they can play that role and eventually tie up with multinational companies to see successful commercialisation.

What are the factors which decide the therapeutic area a company wants to do its research in?

Kamboj: You have to look at it from the unmet need point of view. Generally, market size is driven by how successful the treatments are. I give you an example of neuropathic pain. People feel that there are so many pain drugs. Not true. Neuropathic pain, or chronic pain, actually has no drug that successfully treats it. Most drugs in that segment are either sedative in nature or do something to make it less. But they are actually not treating it. So, neuropathic pain has huge unmet need. You have to look at the disease pathology.

Joshi: By definition, research on innovation means looking for something which is not there. Industry would focus research in areas where there is unmet medical need. Unmet doesn’t only mean total lack of drugs in the market. There may be new diseases appearing.  A classic example is neuropathic pain where not much suitable treatment is available. Many of the drugs show huge side effects. There is unmet medical need to make efficacious drugs. There may be drugs in market which are costly. Obesity, diabetes, mainly the complex diseases with increasing incidences globally or nationally, need focus from industry.

Sapatnekar: It’s a question of addition. Notwithstanding the efforts that have gone in, in 75% of cases success has come by accident. You are looking at something and something else pops up accidentally. This is the reason NCEs are money guzzlers. You have to keep sowing the seeds, which will become saplings. The fruition is generally witnessed by the next generation. That is the next generation of scientists.

Sharma: Any research looks at a 10-15 year horizon. You are taking a call on something today, and you don’t know what will develop tomorrow. So you look at what the competition is like. How many other companies are looking at this field, what is the level of progress they have made. What is the efficacy. And what is that you have which is unique and that which you want to push through. Because you are not going to spend 8-10 years of time and money if you don’t see something which would be the differentiator and for which you can get an IP that you will commercialise.

The NCE pipeline has a clear focus on cancer and diabetes, both in India and overseas. With much focus on these areas,  will it increase chances of more of ‘me-too’ drugs coming out?

Kamboj: ‘Me too’ is not a bad word, as what it says is that it’s a lower risk, it’s still innovation. Biggest example of ‘me too’ category is Lipitor, I believe, the fifth one in that category (statins). Nobody wanted to in-licence it, as there were few other molecules that were way ahead. And Lipitor became the biggest blockbuster and peaked at $13 billion per year in a market where there were several drugs ahead of it.

So following in that category is not a bad thing as there is significant room for improvement. Even in successful areas like cardio vascular, there is need for safer drugs. Innovation is not the domain of the Big Pharma. Most of their drugs are discovered by other people, the small pharma. That’s where the actual innovation lies. And all of Indian pharma, on global scale, is small pharma. Innovation is doable even with smaller budgets, but it has to be done right, in a competitive environment. Skills have to be improved.

Sapatnekar: How many drugs are there that are cheap as well as effective? Not many. So there is scope. There is nothing like ‘me too’ drugs.

Sharma: If it is an NCE, then it can’t be a ‘me too’ drug. Because NCE, by definition, means it’s a new molecule and capable of IP registration. As long as there is an unmet need, there is a molecule which needs to be discovered. Take Prevnar of Wyeth. I am aware that competition is doing research. It doesn’t mean that they are in a ‘me too’ category, it’s just that they are looking for a different efficacy, maybe different population group. You need to evolve.

Joshi: When you talk of a compound which has come from your research, there may be other drugs, other players, but there is still scope for innovation for companies. Also, patients expect some improvement in terms of product differentiation, efficacy.

There was a reference of unmet medical needs. Now, the WHO categories malaria, dengue, kala azar as neglected diseases. Why is there low research in
these areas?
Kamboj: Initially, the innovation was only done in advanced markets. Most of these disorders were not their problem. They never focused on it. India is advancing; there are incidences of these disorders.

Joshi: If you look at the total NCEs that are in the market from 1980s till today, only 3-4% are targeting these diseases. You need to consider why there is unmet medical need for these diseases. Is it because the old drugs are not working because the bugs have developed resistance? It needs extensive basic bioscience research that is lacking, in a global context. Government funding may give a solution. It demands extensive research. In the western world, government spends huge amounts, varsities get huge grants. This is where we differ from the West. Interaction between the industry, varsities and academics is lacking. We are working in isolation.

Sharma: There are some companies in this area, Bharat Biotech, Advinus, Lupin, Ranbaxy. So I think there is focus. With MNC focus coming in emerging markets, I don’t think they can ignore these areas for long. I think the more important aspect is that a lot of basic research comes from varsities. We need to strengthen that in India. If we get that in place, a lot of unmet need for the industry to do research will come through. The government, academia and industry need to sit and decide. It’s not that the government doesn’t have an agenda, but it needs to be more focused.

Sapatnekar: Talking selectively of kala azaar, not much is happening. It needs managerial efficacy and planning. Push has to come from the government as it is the poor who is suffering.

We have companies in NBEs also. To what extent is it more difficult to bring out a NBE compared with an NCE?
Joshi: In NBEs, we have some companies like Biocon. But many companies are in the process of capability building, front-end for marketing, back-end for technology. There is inadequate knowledge in terms of IP situation for NBEs. The whole process is not well charted out as in the case of NCEs. It’s very challenging. Indian companies have been doing NCEs for 5-10 years.

Kamboj: India is making inroads into biosimilars. That itself requires very different skill-sets. In European Union, if you want to bring your biosimilars, you have to produce it. Even if you are using the same protein, each one has unique challenges. There are chances of variations. On the NBEs front, a lot of fundamental research is needed. Pennies versus dollars — that’s the scale for bringing out NCE versus NBE. It’s about 100 times more.

Sapatnekar: NBEs is where the future lies.

What about funding issues? Are investors looking at funding NBEs/NCEs?
Sharma: I think globally also the biotech industry is struggling to get the right funding. Companies are learning how to use cash prudently. Biotech is a field far more complex,
with no visibility on IPRs, and then getting finance is tough. In research, one out of six million molecules is successful. You need to take a bet on what’s going to be the right one. In India, I don’t think the financial services industry has the capability of understanding that. On the whole, there is financing available, but I don’t know whether it is in the research area.

When will India get its first novel drug?
Sharma: Some are in phase II, III, one can’t predict. They see 2011, 2012, 2013, 2014.

Joshi: Though they are in phase II, III, at any stage they can be withdrawn. Sometimes, additional phase III trials are needed, depending on the regulatory agencies. By 2014-2015, we should expect some launch. We are optimistic.

Kamboj: The NCE should work globally, and not just in India. Otherwise, it won’t have much of an impact.

Sapatnekar: It will happen five years from now. 2014.