Tailored Therapies

 In Health

Vijay Chandru / Chairman & M.D Strand Life Sciences

How did the field of personalized medicine emerge? What were the early beginnings?
Vijay Chandru (VC) : Personalized medicine as a practice has been around since the time of Hippocrates, who said, “It’s far more important to know what person the disease has than what disease the person has”. The early beginnings of personalized
medicine were probably influenced by the field of hematology for compatibility testing of blood transfusion between donors and patients. Around the 19th century, advances in the field of microbiology and biochemistry allowed us to understand the
underlying cause of disease and its biology. More recently, the discovery of the DNA structure by Franklin, Watson & Crick
helped us understand diseases at a genetic level, which has significantly contributed towards the emergence of personalized medicine.
What factors have shaped the emergence of personalized medicine?
VC : The development of Trastuzumab (Herceptin®) in 1998 for treating HER2 positive breast cancers heralded the emergence of personalized medicine. Our understanding of cancer genetics helped develop a drug that could target a very specific population with a disease subtype. Later, the discovery and success of Imatinib to treat chronic myelogenous leukemia (CML) proved to be a turning point for developing targeted therapies. An example of a blocking use of pharmacogenomics involves people infected with the human immunodeficiency virus (HIV). Before prescribing the antiviral drug abacavir (Ziagen), physicians now routinely test HIV-infected patients for a genetic variant that makes them more likely to have a bad reaction to the drug. However, the most important factor for the emergence of personalized medicine and its present influence is due to the completion of the Human Genome Project in 2003, and the advent of Next-Generation Sequencing (NGS) which have created a downward spiraling effect on the cost of sequencing and a gradual abandonment of the “one shoe fits all” approach to treatment decisions. The world of healthcare now has a choice on whether to continue to singularly focus on a very successful century of “curative medicine” or to blend in “prospective healthcare” which involves personalized, predictive, preventive and participative care.
How is the industry (of personalized medicine) playing out across the globe? especially the US, Europe, and Japan? What, if any, are the ethical, regulatory issues and financial-legal issues?
VC : The personalized medicine industry is an emerging space across the globe. The main players in this area are pharma companies that develop targeted therapies for oncology, or orphan drugs for rare inherited conditions, and genomic testing laboratories that provide genetic or pharmacogenomic testing. In  the US for example, some of the early movers in genomic testing are Myriad Genetics, Foundation Medicine, and Invitae. Perhaps, the US is one of the most matured markets for personalized medicine, because it has a supportive ecosystem. They have been able to create an end to end program or continuum for personalized medicine, starting with discovery in the laboratory, to the application of that discovery in the clinic (bench to bedside). The efforts in the US personalized medicine space are augmented by large government funding programs such as the President’s Precision Medicine Initiative (PMI), which encourages research & discovery by academia or commercial enterprises. These discoveries can lead to the development of drugs and therapeutics by pharma. In the UK, similar efforts are underway through the government’s program to sequence the genomes of people under the 100,000 Genomes Project. Some of the issues that the industry faces across the globe are related to unclear regulations or non-availability of guidelines for the development and usage of laboratory developed tests (LDTs). This poses a challenge when it comes to proving the efficacy or clinical utility of genomic tests in the clinical care setting, and the corresponding health insurance coverage. While countries such as the US and the UK have government supported programs, in addition to private players supporting precision medicine R&D and commercialization, globally, the industry has relied on exclusive funding by private players which has not accelerated the progress of precision medicine due to financial considerations. Patient privacy and data protection is also a crucial area of debate across the globe. For example, Strand’s technology platforms follow the best practices and are certified to be HIPAA compliant. If labs and diagnostic companies are regulated to follow the regimes of NABL, CAP, and ISO in a genuine way,
these will automatically ensure security and ethical use of data. At Strand, we have an internal Institutional Ethics Review Board
that oversees and clears all our processes as well as the specific tests that we launch. It may be time for a global legislation along the lines of a “genomic information non-discrimination act” (GINA was passed in the US in 2009) that would protect citizens from misuse of their genetic data.
Has personalized medicine, especially in oncology, become the standard of care in the US? What policy initiatives are driving the growth of personalized medicine in the US & UK?
VC : Personalized medicine has had a major impact in US healthcare, especially oncology. The discovery and success of Trastuzumab and Imatinib allowed the adoption of personalized medicine for oncology. Targeted therapies coupled with companion diagnostics have become a standard of care for many of the cancers (lung, colon, melanoma), and sometimes offered as the first line of therapy for patients. Another important policy reason for early adoption is the support of payers, both public payers like Medicare in the US and NHS in UK and private insurance companies that reimburse the pharma, laboratory, clinic or patient as the case may be for both testing
and treatment involved in the practice of personalized medicine in these countries. The success of such landmark events has encouraged the US and the UK to undertake policy initiatives driving the growth of personalized medicine. The major driver has been the government funding of genomics research and drug development. Programs such as the PMI, Cancer Moonshot, and 100,000 Genomes are aimed at accelerating the promise of personalized medicine. Knowing that the effects of such large-scale projects would generate enormous amounts of information, the FDA has built up infrastructure to tackle such challenges. For instance, they have set up numerous task forces, committees, programs, specialized laboratories, and collaborative projects with industry to advance the knowledge in genomics, and accelerate drug development and approvals. Laboratory regulations and standards such as CAP and CLIA have been set up to ensure that there are standardizations and adherence to quality across genetic testing laboratories.
Strand has been a pioneer in personalized medicine in India. What are your thoughts on the growth of this industry in India? What are the hurdles?
VC : Strand, with its history of excellence in innovative genomic research and solutions, pivoted into the genomic testing/ personalized medicine space in India about four years ago. During that time, there was neither market nor an understanding of genomic testing. We had to start the process of market development from scratch, by educating the medical community about genetic tests, and its benefits for effectively managing diseases such as cancer and inherited genetic disorders. Strand has had the opportunity to pioneer the complex field of genomic testing in India by offering robustly validated assays run in CAP/ISO certified environments. Along with us, there are few other players in the market offering genetic tests. We believe that we will continue to be the market leader in the space of complex multi-genic testing in India and will grow the market for the whole field. This is an emerging area of personalized and
precision medicine which is happening now in India just as it unfolds in the West as well. If you see the West, the treatment landscape is slowly but steadily shifting from a ‘one-size-fits-all’ approach to a personalized approach. Even in India, we see this trend taking shape in pockets. This approach will grow to become widely adopted mainly due to the genetic diversity in the Indian population. In oncology, for example, physicians have started adopting the personalized medicine approach to treating their patients. These indicators augur well for the growth of this industry. However, a lot of work needs to be done to reach a stage where personalized medicine can become a mainstream approach in the clinic. Physicians mainly cite the lack of guidelines or published clinical utility data for them to adopt and follow while treating a patient. Moreover, most of the data that is published in the medical literature are based on Caucasian populations. We will need to design and carry out India-specific population studies in order to ensure that the genetic variants that are identified are relevant and targetable in terms of treatment or disease management. The good news is that Strand has already written clinical reports for over 5000 patients in India and several publications are out and in press that are beginning to shed light on the clinical genomics of South Asian ethnicities. However, there is the universal challenge that we have only learned to interpret about 20% of the genes in human DNA. So there is a lot of signal from genetic testing that no body know how to interpret. Knowledge is expanding rapidly and highly trained and large scale knowledge curation is required to address this challenge. Strand has a very special approach to this, our secret sauce, which has made us a global leader in interpretation. From an affordability perspective, the cost and availability of targeted therapies in India put the promise of personalized medicine out of reach for a large section of the population. Unfortunately, the cost of genomic testing is also significantly on the higher side due to import duties that add to the cost of reagents that are required to run diagnostic assays. However, at Strand we are trying to reduce the cost burden for patients by innovating in both chemistry of reagents and in the use of advanced artificial intelligence (AI) based pipelines to make a huge impact on the affordability of our tests.
What elements should come together for greater adoption of personalized medicine? What role can Government, industry, and civil society play for this industry to grow in India?
VC : Strand is participating in bringing personalized and precision medicine to the Indian healthcare establishment in a responsible, ethical and scientifically validated manner. We are working with the medical establishment to define new guidelines for bringing this practice into the mainstream of medical practice, and are carrying out exceptional translational research with our partners in Mazumdar-Shaw Medical Center at Narayana Health which will put personalized and precision medicine in India on the global map. India has been a global leader in affordable medicines, affordable surgeries, and affordable hospital care. There is no reason we cannot be a global leader in affordable personalized and precision medicine. In order to realize this vision, the government should play a major role in providing research grants or funding to undertake genetic studies based on the Indian population. The government should also set up India-specific guidelines for the development of diagnostic tests, accelerate drug development, and guide the industry appropriately. The medical community should look at the advantages of moving towards a preventive healthcare model, rather than a reactive model. An example would be BRCA testing to identify if an individual is at risk of developing breast cancer over their lifetime. Knowing a person’s risk in advance can help in preventing or managing the disease, which will not only help in the well-being of the patient but also avoid unnecessary costs with regard to treatment. The entire community should also come together and set up guidelines for the practice of personalized medicine in their respective specialties. At the medical education level, administrators should seriously consider incorporation of genetics as a curriculum in the undergraduate medical program. In the next few weeks, Strand will publish compilation of detailed case-studies which will be a great beginning in medical genomics pedagogy for Indian healthcare professionals. The industry will have a responsible role to play in the advancement of the state of knowledge in this space by conducting novel research and extensive clinical validation studies. They will also have to work with the government and insurance providers to figure out an approach to ensure that these life changing tests and drugs are covered by insurance so that every citizen in the country can reap the benefits of advanced medical care. Lastly, the industry can play a significant role by educating the civil society by creating awareness about the benefits of personalized medicine.
How do you see the field evolve globally in the next 5-10 years?
VC : In personalized and precision medicine, genetic testing can help with choosing the right drug and the right dose for the individual patient. This has been effectively demonstrated in the care of many cancer patients. There are also great opportunities in preventive care of people whose risks for diseases can be estimated from genetic dispositions and appropriate preventive measures including many lifestyle changes, can be effectively brought to bear. Cardiac disease, Neurodegenerative, and Cardiovascular disease are particularly significant in adults and seniors. Countries that have already adopted or adopting personalized medicine will see themselves in a very advanced position in the coming years. Their health outcomes and economics will be defined by the success of personalized medicine. In addition, global initiatives such as the PMI, 100,000 genomes, and other initiatives will culminate in the next 5-10 years, providing the much-needed validation and utility for the widespread clinical adoption of personalized medicine.
In the future, electronic health records will be linked to our personal genomic data from which insights can be derived for tailoring treatments and providing health advice. The field of personalized medicine will eventually evolve towards a point where our health is not just managed and treated by physical symptoms or broad molecular observation, but a combination of genomic, proteomic and epigenomic data points, coupled with medical imaging, minimally invasive methods such as liquid biopsies, and interventions such as gene therapies.

Vijay Chandru

from : www.birac.nic.in/webcontent/BIRAC_i3_Dec_2016.pdf 

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