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A Patient-Centric State Initiative To Revolutionize Disease Treatment

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In his State of the Union address, just before the recent visit to India in January 2015, President Barack Obama articulated the need to develop “Precision Medicine” in his country – a bold, giant and perhaps unprecedented State initiative to remarkably improve effectiveness of disease treatment.

To set the ball rolling, in his budget proposal for the year 2016, President Obama earmarked an amount of US$ 215 million for this purpose. This includes an allocation of US$130 million for the National Institutes of Health (NIH) to create a national research database of about a million American volunteers by studying their genetics together with other relevant factors, such as the environments they live in and the microbes that live in their bodies.

‘Precision Medicine’ initiative is similar to path breaking 13-year and US$3 billion Human Genome Project, that has formed the bedrock of modern genomics, President Obama said. He also expressed hope that the private healthcare sector too, including universities and foundations, will get involved to “lay the foundation” for this new initiative of the Government for the interest of patients.

Why is this approach so relevant in today’s healthcare?

In an article published in the ‘British Medical Journal (BMJ) in October 2012, Richard Smith - an editor of BMJ until 2004 and a Director of the United Health Group’s chronic disease initiative wrote:

“Doctors know that many of the patients they treat with drugs will not benefit. Many patients know that too.”

Dr. Smith also emphasized, for centuries medicine classified diseases by what could be seen, felt, and smelt. Thereafter, medical scientists in this area started defining diseases anatomically, physiologically, and biochemically. Even today, this is by and large the paradigm where most medicines fall.

Smith underscored, because of imprecise diagnosis the treatment also becomes haphazard. There is big variation in how individuals respond to drugs and yet that variation is not usually recorded. The regulators approve drugs based on their average performance even today.

The White House release also reiterates, most medical treatments have been designed for the “average patient.” This “one-size-fits-all-approach,” treatments can be very successful for some patients but not for others.

This calls for broadening the scope of disease treatment – from the conventional and error-prone ‘Disease Oriented’ approach, to relatively more unconventional and better targeted with greater value – ‘Patient-Centric’ ones, wherever needed.

Two current trends:

To address this key deficiency in the effective treatment of several dreaded diseases for many patients, following two are the current trends, as stated by William Pao, M.D., Ph.D., who led Roche’s Oncology Discovery & Translational Area research unit since May 2014:

  • We now know that on a molecular level every cancer is different – not only between different tumors, but even between different areas within a single tumor! This means that we need to match the right drug to the patient who we know will respond best to the drug, at the right time during the course of treatment.
  • Patients will have their tumors profiled not only for genetic drivers, but also for predictive immunotherapy markers at different time points in their course of treatment.

Personalized and Precision Medicine:

The above trends in the endeavor of making treatments more patient specific – thus more effective, have thrown open scientific discourse and intense research on ‘Personalized’ and ‘Precision’ medicines.

As Pfizer has described in its website:

Personalized Medicine is a unique approach to medical practice in which the individual aspects of a patient are directly considered to guide treatment planning, including his or her genetic make-up, key biomarkers, prior treatment history, environmental factors and behavioral preferences. This approach can be used to optimize pharmaceutical treatments and overall care.

Whereas, Precision Medicine is an approach to discovering and developing medicines and vaccines that deliver superior outcomes for patients, by integrating clinical and molecular information to understand the biological basis of disease. Precision medicine is the biopharmaceutical research and development paradigm that will help enable more patient-centered clinical practice, including treatment decision-making based on genetic information – an emerging standard now often described as “personalized medicine”.

As President Obama said while announcing the proposal on January 30, 2015, ‘Precision Medicine’ promises delivery of the right treatment at the right time, every time, to the right person.

He also said that the new effort will “bring us closer to curing diseases like cancer and diabetes…and give all of us access to the personalized information we need to keep ourselves and our families healthier.”

‘Precision Medicines’ Dominate Oncology segment: 

In the European Society for Medical Oncology (ESMO) 2014 Congress, pharma majors reported their latest advances on precision medicines in the cancer care. Bristol-Myers Squibb, Roche, AstraZeneca, GlaxoSmithKline (GSK), and Merck & Co. were among the companies presented updates of their most promising cancer drugs closer to this area.

According to a large pharma lobby group in the United States – The Pharmaceutical Research and Manufacturers of America (PhRMA):

“Recent advances in diseases such as cancer and cystic fibrosis are delivering on the promise of targeted treatments, and between 12 and 50 percent of all compounds currently being researched by the industry are potential personalized medicines. These advances hold great promise in improving patient outcomes and controlling costs by targeting the right medicines to the right patients.”

‘DCAT Connect’ Report of September 2014 also indicates significant increase in ‘Precision Medicines’ in the pipelines of the leading global pharma companies, which is a key change over the past decade.

In 2013, targeted therapies increased their share of the global oncology market, accounting for 46 percent of total sales, up from 11 percent a decade ago. According to IMS Institute for Healthcare Informatics, the global oncology drug market reached US$ 91 billion in 2013 with CAGR of 5.4 percent from 2008 to 2013.

Taking note of this trend, it appears that in the near future ‘Precision Medicines’ would possibly be the most promising class in the treatment of cancer, particularly in breast cancer, lung cancer and certain types of leukemia. This is mainly because medical scientists are already quite acquainted with the molecular signatures of different types of cancer related tumors.

Medical scientists and researchers are also working on ‘Precision Medicines’ to more effectively address many other diseases, such as, diabetes, cardiovascular and ailments related to several types of infections.

Increasing potential:

Realization of the potential of ‘Precision Medicines’ to improve care and speed the development of new treatments has just only begun to be tapped.

In recent times, scientists and researchers have accelerated efforts to understand more about biomarkers for this purpose. A study conducted by the German Association of Research-Based Pharmaceutical Companies (vfa) indicates that more than 20 percent of clinical trials carried out since 2005 focused not just on agents, but also on biomarkers. Before 1990, only one in twenty clinical trials addressed biomarkers.

According to another report, last year, 20 percent of all new drug approvals in the United States were for “Precision Medicine” treatments. This vindicates, yet again, the immense potential to turn genetic discoveries into innovative disease treatments for patients.

A bold state sponsored research initiative:

State funded, ‘Precision Medicine’ initiative is a bold new step of the American Government to revolutionize improvement in healthcare and treating disease. It is expected to pioneer a new model of patient-powered research that promises to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients.

As the White House release reiterates, most medical treatments have been designed for the “average patient.” As a result of this, “one-size-fits-all-approach” treatments can be very successful for some patients but not for others. This is changing with the emergence of ‘Precision Medicine’, an innovative approach to disease prevention and treatment that takes into account individual differences in people’s genes, environments, and lifestyles.

In this process, ‘Precision Medicine’ gives clinicians tools to better understand the complex mechanisms underlying a patient’s health, disease, or condition, and to better predict which treatments will be most effective.

Opposite view:

In an op-ed titled, ‘Moonshot’ Medicine Will Let Us Down, published recently in The New York Times, the author argued with his differing viewpoints.

I am quoting below three of those arguments:

  • “For most common diseases, hundreds of genetic risk variants with small effects have been identified, and it is hard to develop a clear picture of who is really at risk for what. This was actually one of the major and unexpected findings of the Human Genome Project. In the 1990s and early 2000s, it was thought that a few genetic variants would be found to account for a lot of disease risk. But for widespread diseases like diabetes, heart disease and most cancers, no clear genetic story has emerged for a vast majority of cases.”
  • “Another unexpected finding of the Human Genome Project was the problem of ‘missing heritability.’ While the statistics suggest that there is a genetic explanation for common conditions and diseases running in families or populations, it turns out that the information on genetic variants doesn’t explain that increased risk.”
  • “The idea behind the “war on cancer” was that a deep understanding of the basic biology of cancer would let us develop targeted therapies and cure the disease. Unfortunately, although we know far more today than we did 40-plus years ago, the statistics on cancer deaths have remained incredibly stubborn.”

I am sure, you will analyze the above points with the facts that you have at your disposal on this subject to arrive at a logical conclusion.

Current Applications:

Though these are still early days, initial benefits of ‘Precision Medicines’ have been reported in many areas, such as:

  • Genetic analysis of patients dealing with blood clots: Since 2007, the U.S. Food and Drug Administration has been recommending genotyping for all patients being assessed for therapy involving Warfarin.
  • Colorectal cancer: For colon cancer patients, the biomarker that predicts how a tumor will respond to certain drugs is a protein encoded by the KRAS gene, which can now be determined through a simple test.
  • Breast cancer: Women with breast tumors can now be effectively screened to determine which receptors their tumor cells contain.
  • Cystic fibrosis: In America, patients with a rare form of cystic fibrosis now can choose a drug designed specifically to target the genetic defect causing their illness. Specialized medical centers, such as “individualized medicine centers” at the Mayo Clinic, are also available to the patients for effective treatment.

Ethical issues:

While following this pursuit of excellence of the genetic scientists in the realm of disease treatment, some experts have reportedly raised flags of caution. They strongly feel that DNA code sequencing brings to light a “very real privacy concerns” of individuals.

GeneWatch UK is an organization that investigates how genetic science and technologies will impact on our food, health, agriculture, environment and society. They have been strongly arguing, if genome sequencing is extended to entire population, individuals and their relatives could then be identified and tracked by matching their DNA with the genome stored in the respective health records. This move, as contemplated by them, could “wipe out privacy” with an impact on the society.

Thus, the ethical and social issues in the development of ‘Precision Medicine’ primarily in the area of genetic testing need to be effectively addressed, sooner.

Conclusion:

The quest for moving away from conventional and error-prone ‘Disease Oriented Treatment’ paving the way for unconventional and value added individual patient-specific ones, may soon come to fruition.

Advances in ‘Precision Medicine’ have already led to powerful new discoveries and several new treatments that are tailored to specific characteristics of individuals, such as a person’s genetic makeup, or the genetic profile of an individual’s tumor.  This is leading to a transformation in the way the world can treat diseases such as cancer.

Patients with breast, lung, and colorectal cancers, melanomas and leukemia, for instance, should be provided with facilities in specialist hospitals to undergo molecular testing as a part of patient care, enabling physicians to select treatments that improve chances of survival and reduce exposure to adverse effects.

Although, the potential for precision medicine to improve care and speed the development of new treatments has only just begun to be tapped, some skeptics do say that tailoring medical treatments to individual characteristics of each patient is both overly optimistic and cost-prohibitive.

Be that as it may, in the balance of probability the benefits of prudent use of ‘Precision Medicine’ far outweigh the concerns expressed. This evolving new paradigm would help saving not just significant expenses, but also precious time that is usually spent on ‘trial-and-error treatments’, by enabling clinicians to determine quickly which therapies are most likely to succeed.

Though lot many grounds would still need to be covered in this area, the State sponsored ‘Precision Medicine’ initiative of America to revolutionize disease treatment, in my view, is indeed a laudable one, every way.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

“Meeting Unmet Needs of Patients”: A New Direction

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The much-hyped phrase of the global pharma majors – ‘meeting unmet needs of patients’, is very often used to create an aura around newer patented drugs of all kinds, from original to banal, including evergreen varieties such as:

Evergreen Drug/Brand Medical Condition Original Drug/Brand
Levocetirizine (Vozet) Allergies Cetirizine (Zyrtec)
Escitalopram (Lexapro) Depression Citalopram (Celexa)
Esomeprazole (Nexium) Acid reflux Omeprazole (Prilosec)
Desloratadine (Clarinex) Allergies Loratadine (Claritan)
Pregabalin (Lyrica) Seizures Gabapentin (Neurotonin)

I do not have any terrible issue with this usage, as many stakeholders, including various governments, have already started differentiating between the ‘Chalk’ and the ‘Cheese’ kinds of patented products and contemplating future course of action, accordingly. The recent development in South Africa is one such example.

That said, there is now a greater need to ponder over the much bigger picture in the same context and direction, which would improve predictability of treatment outcomes by manifold. Simultaneously, such R&D initiatives would help reducing the overall cost, especially for dreaded diseases like cancer, mainly through highly targeted drugs and consequently avoiding the risk and associated wastage, as often happens with the prevailing ‘trial and error’ therapy approach, thereby benefitting the patients immensely. This is mainly because no drug is 100 percent effective with inconsequential side-effects for all patients of any disease type.

Genetics and Genomics Science made it possible:

With already acquired knowledge in genetics, genomics and genome sequencing capability, it is now possible to precisely predict a person’s susceptibility to various disease types and proactively working out measures to help either avoiding ailments, such as, non-infectious life threatening and chronic diseases altogether, if not, making their treatment more predictable and less expensive, as stated above.

If organized efforts are made to extend the application and benefits of this science to a larger section of population, those R&D initiatives can really be construed, unquestionably, as ‘meeting unmet needs of the patients’, just as ‘first in kind’ category of innovative drugs are recognized by the scientific community and the civil society as a whole.

A treatment revolution in the offing:

Expectations are rapidly building up that evolving genetics and genomics science based technological know-how would ultimately revolutionize the practice of medicine ushering-in the pathway of personalized medicine for a large number of patients.

Definition: 

A report from the Tufts Center for the Study of Drug Development defines personalized medicine as “Tailoring of medical treatment and delivery of health care to individual characteristics of each patient, including their genetic, molecular, imaging and other personal determinants. Using this approach has the potential to speed accurate diagnosis, decrease side effects, and increase the likelihood that a medicine will work for an individual patient.”

The aim: 

The aim of personalized medicine is, therefore, to make a perfect fit between the drug and the patient. It is worth noting that genotyping is currently not a part of clinically accepted routine. However, it is expected to acquire this status in the western world, shortly.

To give a very quick example, genetic differences within individuals determine how their bodies react to drugs such as Warfarin – a blood thinner taken to prevent clotting. It is of utmost importance to get the dosing right, as more of the drug will cause bleeding and less of it will not have any therapeutic effect.

In the field of cancer, genetic tests are now being done by some oncologists to determine which patients will be benefited most; say with Herceptin, in the treatment of breast cancer.

Thus, with personalized medicine the health of a patient will be managed based on personal characteristics of the individual, including height, weight, diet, age, sex etc. instead of defined “standards of care”, based on averaging response across a patient group. Pharmacogenomics tests like, sequencing of human genome will determine a patient’s likely response to drugs.

Disease prevention: 

In addition, such medicines would help identifying individuals prone to serious ailments such as, metabolic, cardiac, endocrine, auto-immune, psychosomatic, including cancer of various types; enabling physicians to take appropriate preventive measures much before disease manifestations and in that process would help containing the overall treatment cost.

Cost of genome sequencing:

Sir John Bell, Professor of Medicine at Oxford University, reportedly said in early December 2012 that personalized medicine for all could soon be a clear possibility, as everybody will be able to have their entire DNA make-up mapped for as little as £100 (Rs.10, 000 approx.).

This estimate seems to be realistic, as the price of genome sequencing has fallen by 100,000-fold in 10 years. This cost is expected to further decline, as genome of any person essentially remains unchanged over time. Thus, this information might become a part of an individual’s medical record allowing the doctors to use it as necessary.

Summary of key advantages: 

To summarize, the expected benefits from personalized medicine, besides very early diagnosis as stated above, are the following:

1. More Accurate Dosing: Instead of dose being decided based on age and body weight of the patients, the physicians may decide and adjust the dose of the medicines based on the genetic profiling of the patients.

2. More Targeted Drugs: It will be possible for the pharmaceutical companies to develop and market drugs for patients with specific genetic profiles. In that process, a drug needs to be tested only on those who are likely to derive benefits from it. This in turn will be able to effectively tailor clinical trials, expediting the process of market launch of these drugs.

3. Improved Healthcare: personalized medicine would enable the physicians to prescribe ‘the right dose of the right medicine the first time for everyone’ without any trial or error approach, resulting in much better overall healthcare.

Current use:

Though these are still the early days, initial usage of personalized medicine is now being reported in many areas, such as:

Genetic analysis of patients dealing with blood clots: Since 2007, the U.S. Food and Drug Administration has been recommending genotyping for all patients being assessed for therapy involving Warfarin.

Colorectal cancer: For colon cancer patients, the biomarker that predicts how a tumor will respond to certain drugs is a protein encoded by the KRAS gene, which can now be determined through a simple test.

Breast cancer: Women with breast tumors can now be effectively screened to determine which receptors their tumor cells contain.

In addition, this approach would also help clinicians to determine which particular therapy is most likely to succeed on which patient.

Present outlook: 

A September 2013 article published in Forbes Magazine titled, “Personalized Medicine May Be Good For Patients But Bad For Drug Companies’ Bottom Line” says, although personalized medicine offers tremendous potential for patients, because of the dual burdens of expensive clinical trials and diminished revenue potential, the concept may become unsustainable in the long term, the attitude of regulators will be critical to drug companies’ willingness to embrace personalized medicine, and to its wider application.

In my view, for greater interest of patients to ‘meet their unmet needs’ global pharma, majors, academics, respective governments and the drug regulators should find a way out in this new direction, sooner.

Indian initiatives:

Some companies, both well known and lesser known, are making collaborative progress, keeping low profile, in the genome sequencing area in India, which will ultimately make expensive treatments, such as cancer, more predictable and simultaneously affordable to many.

The concerns:

While the progress in the field of personalized medicine is quite heartening, some experts have reportedly been sounding a note of caution. They strongly feel that DNA code sequencing brings to light a “very real privacy concerns” of individuals.

The key argument being, if genome sequencing is extended to entire population, individuals and their relatives could then be identified and tracked by matching their DNA with the genome stored in the respective health records. This move, as contemplated by the opponents, could “wipe out privacy” with a significant impact on the society.

A paper published in ‘Scientific American’ dated January 2014, titled “What Fetal Genome Screening Could Mean for Babies and Parents” deliberated that today doctors are closer than ever before to routinely glimpsing the full genetic blueprints of a fetus just months after sperm meets egg. That genomic reconstruction would reveal future disease risk and genetic traits even as early as the first trimester of pregnancy – raising another ethical issue that could hugely impact parents’ decision threshold for deciding to terminate a pregnancy or influencing how they rear their child.

Thus, all these ethical and social issues in the development and usage of personalized medicine must be appropriately addressed under a well deliberated ethical, social, legal and regulatory framework of each country.

Conclusion:

Though in Europe and to some extent in the United States, treatments based on personalized medicine have already been initiated, we are still in a nascent stage for this novel concept to get translated into reality for the benefit of a much wider population across the world.

Lot of grounds may still need to be covered, especially in the realm of medical research and also to work out the regulatory pathways for personalized medicine in healthcare by the pioneers of this great concept and more importantly by effectively addressing the ethical concerns raised on this subject.

If collaborative initiatives are taken jointly by academia, R&D based global pharma majors and medical diagnostic players towards this new direction with a clearer focus and  supported by the law makers, a huge unmet needs of patients will truly be met, giving yet again a fresh impetus to the much hyped phrase “Meeting Unmet Needs of Patients”, though in a refreshingly new direction.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.