Dr Reddy’s Laboratories Senior VP on the Asian Pharma Market & Early Phase Clinical Trials

In March 2012 the number of clinical trials registered in Asia reached almost 20,000.  Also, we have seen significant increase in the number of early phase clinical trials conducted in Asia but more and more multinational pharmaceutical companies are planning early phase clinical trials in the next two years. Dr. Akhilesh Sharma, Senior Vice President and Global Head of Global Medical Affairs at Dr. Reddy’s Laboratories, joins Pharma IQ to discuss early phase clinical trials and growth in the Asian pharma market.  

Pharma IQ: What emerging trends are you witnessing in early phase clinical trial?

A Sharma: The most important what I see is the proof of concept which needs to be achieved at the early stage and this is done with the help of target engagements and, clearly, now the targets which are defined are more based on specific areas.  Either it is a specific target related to a particular disorder, like you know, I was working on a target in diabetes and that’s a target on an enzyme for increasing blood glucose levels through liver into blood. These targets would work on some specific related areas in liver and blood, which would help them reducing the blood glucose. So, if you’re able to show a good engagement and remission of the enzyme, then you are able to predict what could be the possible outcome in the clinical trial.  So the predictability improves with the percentage target engagement and this is one of the major changes which happening across in most of the leads which are being developed. 

The other change is including biomarkers into the development phase and this also helps in not only defining what biomarkers, who should be the patient group, what is the kind of patient profile who would respond to the drug, but it also helps in arriving or coming to a consensus that, during the phases of development, during the next phases of development of the drug, what biomarker probably can get in as either a therapeutic marker or a prognostic marker.  So these are the few, couple of changes which I see then.  Then the most important are the way the safety assessments are done, the whole battery of safety assessments and translation medicine, which helps in defining the right patient population or the right kind of volunteers who could be picked up in the early phase at first.

Pharma IQ: Great, and what would you say are the most effect methods for detecting target engagement in clinical trials?

A Sharma: I see that it should be given a lot of importance right from the time a drug evolves from its chemical form.  That is from your medicinal chemistry and, once your medicinal chemistry colleagues have passed on it, one has to really understand what it does, where it works and how much it affects, like what is the quantitative expected outcome from the drug.  Like, you know, the risk of failures would decrease in that case.  I can give an example about an oncology drug which was developed and worked upon like it’s a particular enzyme inhibitor for tumor target. There we found that, if we do inhibition of the particular enzyme, it should be a drug which should be effective and this tested in the animal models and then it was retrieved and data extrapolated to the human beings but it didn’t work there in all tumor types expressing the enzyme except for selected ones.  So it means that, proverbially, it’s not just the specific enzyme expression and one needs to look beyond that in terms of whether it is the other expression which is related to either the other markers, say the other RNA or DNA markers. These were later on picked up, and the predictability was based on those markers for the same drug which actually was supposed to be that particular target inhibitor.  So we may call it as a inhibitor of the specific enzyme but the actual mode of action was more happening through other methodologies like some additional biomarkers which were being affected by the drug which demonstrated in the clinical trials.  But that makes a difference about, you know, how you choose a particular marker and a lot of due diligence is required to be done right in the early stage itself of the development for picking up the biomarker.

Pharma IQ: What do you think is really driving the use of biomarkers in early phase clinical development?

A Sharma: We all know that it involves a huge amount of cost in a drug development and the estimates have been up to US$500 or 750 million for a drug development and, out of that, how much finally would come back because you don’t know.  You are now working on some specific focused indications.  That has started from the cutting into the pockets, the holes.  So we need to plug in that and this could be possible by the biomarkers because the biomarkers not only would help to improve a base for the drug development but they would also help in the final marketing strategy that you’re targeting the right patient population.  And this is what would finally help to achieve what we are talking about, individualised medicine, because I think we are moving from group medicine.  It’s not that a drug is one drug fits all but now we are talking of a drug which should be specific and it should be developed more like your individualised medicine.  So this is what the biomarkers would help to achieve and increase the predictability and success of a treatment outcome.

Pharma IQ: What steps are you taking in your company to improve your translational strategy and aligning preclinical models with the clinical strategy?

A Sharma: We work right from the beginning with the folks who are involved in the preclinical models, the pharmacology colleagues, and the folks who are involved in the biometrics and involved in the biomarkers, aligning all these things together, along with the R&D teams, to work out a complete pathway in terms of what needs to be done going forward, right from the phase one up to the next phase of clinical trials.  This involves a lot of collaboration and a lot of networking along with the colleagues within, as well as outside, the organisation.

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Pharma IQ: What strategies are you putting in place to reduce timelines and prevent early phase failures?

A Sharma: Well, as I told you, one of the things is to do a target engagement study and see that, you know, you’re able to get moving faster to understand the proof of concept.  The other is to design the trial in an adaptive manner so the adaptive design study itself helps to give you an early proof of concept.  Like in the phase one itself you can have a 1A and 1B.  Probably in 1B you could have a model which can give you an early proof of concept, which could help you to decide to move to the next phase or even help you to decide of what possible doses could be selected in the next one.

Pharma IQ: Looking now at the Asian pharmaceutical market, what therapeutic areas in your opinion do you think will be the biggest opportunity in terms of growth?

A Sharma: There is a shift which is happening in Asia as well and the shift is happening from the acute to the chronic disorders.  That is the shift is happening towards some metabolic disorders.  So I see that metabolic disorders are going to be one of the major parts of the Asian markets, the Asian pharmaceutical markets, to drive.  Yes, this comes along with the cardiovascular market.  So, coupled with this, these would be the major ones and including the other major market, which would help to drive or which is actually going to lead the growth, is, I see, as the dermatology market, the skin market, which is significantly more than it is moving forward.

Pharma IQ: The 2nd Annual Early Phase Clinical Trials Asia Summit is returning in August, with other senior figures, including yourself.  What are you most looking forward to about the event?

A Sharma: We’re looking at, you know, in terms of how the knowledge base which is created across in different countries, they could come and share that together and create a good collaborative and a networking environment which would help to leverage on the strengths of each one of us we carry from the different regions and the experiences which we carry.

Pharma IQ: Finally, what would be your predictions for the global pharma landscape, heading towards 2020?

A Sharma: I see Asia evolving as a significantly large market over the next few years and there have been predictions which have been made in the recent past that it would be China which would soon come over and lead their pharmaceutical business by around 2025 and around 2050 it is expected that India would take over and that’s how, you know, the overall Asian markets would be driving the growth for the major part of the world.

Pharma IQ: If you would like to hear more from Dr. Sharma or find out more about the Second Annual Early Phase Clinical Trials Asia summit taking place in Singapore from the 28^th -29^th August, 2012.

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