Translating research into medicine
The pharma industry worldwide is facing flak over drugs causing adverse effects among patients. In such a lean scenario, translational medicine seems to be the only ray of hope. Swapan Bhattacharya, Director and Head, TCG Lifesciences throws light on the concept and the company’s foray in this direction; in conversation wih Sushmi Dey.
How can the concept of translational medicine be instrumental in creating a better pipeline of drugs?
This concept is helpful in creating more consumer- or patient-oriented medicines. There are rare chances of any side-effects or adverse reactions because the drugs developed through the new concept are based on the data available from stratified patient groups and are more specific. This is not a new concept but the process is redefined. With the concept of translational medicine, we are trying to redesign the molecule which means tailoring the design to a point where there are higher chances of success when it goes to the market.
What made TCG foray into translational medicine?
We are a little different from other groups. We do a lot of market research, studies and strategic research to realise our strengths and use it where there is the need. We believe in creating a strategy that has a unique value proposition. We are not doing anything new with our focus on translational medicine, but approaching the drug discovery and development process in a different way. Also, even though this concept might just have initiated in India, globally, the pharmaceutical industry has already recognised it. So going forward, in the next five years, it will pick up in a big way. It gives us hope that by having a sound strategy and a framework already in place, we may be in a position to accelerate because that is clearly the way to go through the future.
Why do you think translational medicine will prove lucrative for Indian pharmaceutical companies?
In recent times the pharmaceutical industry has witnessed a lot of drug failures and there are pressures on drug makers to change the process of drug discovery. It is imperative for the industry to look for a different strategy because the $1.5 billion model is not going to work. Presently, the pharmaceutical industry works on the basis of a discovery and development chain, but very soon the patient population is going to be segmented and you have to change yourself.
With translational medicine you put an additional phase between lead optimisation and Phase III. People call it the ‘learn and confirm’ mode. This phase is instrumental, in the sense that, it will enable pharmaceutical companies to take molecules which seem interesting. Hence, there is a reduction in cost and time involved. Thus the concept of translational medicine is very promising in terms of reduction in cost, time taken in regulatory approval and drug failure.
How will pharma companies benefit from translational medicine?
Pharmaceutical companies often face a heavy loss when molecules show adverse affects on patients after their launch in the market. At times, these loses can be so heavy that a company can be put out of business. This concept can help drugs that are withdrawn from the market, as they can be retained by discovering specific patient groups for whom the drug will have good efficacy and no adverse effects. For instance, interferon, which is a prescribed treatment for hepatitis B patients, is generally known to benefit only 25 percent of the world population. If we restrict the use of interferon to 25 percent and understand the mechanism of action of the molecule to find out why the medicine works on 25 percent of the population and not on the rest, then we can work on another molecule that suits the rest 75 percent. We will be doing nothing new but creating a tailored medicine for tailored patients.
This is just what translational medicines are targeted at. The aim is to find a variation of what has been done. This works in favour of both the pharmaceutical company as well as the patient.
What are the regulatory impediments to translation medicine?
With the creation of privacy laws, such as the Health Insurance Portability and Accountability Act (HIPAA) and Ethical Guidelines for Biomedical Research on Human Subjects (EGBRHS) and stronger internal review board protection, patients must be protected from undue risks associated with research. However, with new regulations patient privacy and consent restrictions have also become more complex for organizations to monitor and manage. Although not an impediment to translational medicine, it is a hurdle that organisations need to overcome. We overcome this obstacle at TCG Lifesciences through the use of our leading thin-client informatics solution to manage our bio-repository of specimens, as well as the associated experimental and clinical data, enabling full compliance with internal standards and government regulations, including HIPAA and EGBRHS.
What are the strides made in this field in India and abroad?
Global pharma is looking at translational medicines in a big way, but in India things have just begun. But the initiatives are bound to take shape in years to come. According to my information, we are the only private player with facilities and infrastructure in place for undertaking research in this segment. Although we are not yet completely capable of handling the activity from start to end, we are developing facilities. We have re-oriented and restructured TCG to undertake projects on translational medicines. We have developed and utilized our strengths and built on a patient base. We are working with lot of entities to create patient base, bio base, blood samples, etc. We are also discovering research areas which are capable of taking inputs. We are primarily screening work informatics platforms and complex set of data that is going to give us information. We are putting all our strengths in place to utilize parts of this chain. However, it will take around seven to ten years to bear fruit.
What are the challenges involved in development of translational medicines?
Translational medicine incorporates aspects of both basic science and clinical research, and therefore requires skills and resources not usually available in a single laboratory or clinical setting. For this reason, many research institutes, university science departments, freestanding clinics and hospitals and isolated molecular medicine entities cannot readily accomplish translational research singularly because these institutions lack the combination of experimental research and clinical investigative expertise needed. Furthermore, organisations that possess these resources are significantly challenged to overcome the internal political and organizational hurdles to integrate these departments. The concept of translational medicine can only operate when there is a cohesive model in place where the experts of different domains work together and share information.
There are also infrastructural constraints. The infrastructure to support translational research is expensive and facilities to conduct genomics and proteomics research are practically non-existent in India. Furthermore, translational research requires the integration of experimental and clinical data. For most organisations this information is captured in multiple legacy systems that are not combined and require significant manual steps to integrate. TCG Lifesciences is in an advantageous position as it has set up preferred access to the needed infrastructure and maintains the leading thin-client informatics solution as our integrated IT infrastructure to manage the data from bench to bedside and back.
Under the new approach of translational medicine, organizations seek to identify genes and proteins that relate to a particular disease or phenotypic effect by analysing patient genomic and phenotypic information gained in discovery and clinical trials. Chemical compounds or biologics are developed that target these identified genes or proteins. By focusing on the target and evaluating effect against diseased tissue, we can transition compounds or biologics to pre-clinical and clinical development with greater chance of success. We can then potentially re-use the specimens as well as the subject and clinical data captured during clinical trials for further discovery research. It is a rather broad concept where scientists and organizations will work collaboratively to discover and develop a molecule for consumers or patients.
This new paradigm in drug discovery and development research emphasizes a bi-directional process of bench to bedside and back. Instead of having a linear flow, like that in traditional research process, translational medicines say that let us do it in continuum. Translational medicine aims at continuing the process of traditional drug discovery and research by circling it back from bedside to bench. The concept of translational medicine characterises the disease better to create distinction between the different manifestations of the disease in different individuals and then uses that data to specifically address those manifestations. This enables researchers to discover drugs that are based on the genetic make up, life style and environment etc.
Contrary to the traditional research process, which is based on the concept of discovering a wonder drug, and presenting it to the consumer, the concept of translational medicine is mostly consumer oriented. This concept also challenges the traditional culture of drug discovery and development, and thus requires a level of business integration and technology infrastructure that transcends a single laboratory.