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A Sine Qua Non to Pharma Success in Digitized World

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A wind of change is now blowing at an accelerated speed – encompassing virtually anything, across the world, including India, with a varying degree, though. It leaves a profound impact on the day to day lives of many, including almost free access to a plethora of information of any kind available in the cyberspace. The way we express ourselves – connect with others – meet our various needs and requirements – make hassle-free financial transactions – increasing transparency – containing corruption, besides scores of others.

Fast evolving digital technology is predominantly catalyzing this paradigm shift. Its weighty impact can also be felt across the global business world, sparing virtually none. Digitally enabled recent GST implementation process in India is just one such example.

Newer technology driven transformation process of overall business ecosystem is sending a strong signal to all concerned to shape up – coming out of their respective comfort zones of the old paradigm, and embracing the new one. Squarely facing this challenge of change is equally critical even to one of the most conservative, tradition bound, and well-regulated pharma industry. It’s rather an absolute necessity for pharma, as virtually all its stakeholders, including the patients and governments, have already started stepping on to the digitized world. The fundamental choice is, therefore, between shaping-up and shipping-out.

In this article, I shall argue on this critical need, based on several recent, pertinent and contemporary research findings on this fascinating space.

Indian CEOs take:

The 20th CEO Survey of 2017 titled, “Being Fit for Growth”, conducted by PwC

reveals that the term ‘digital’ evokes both excitement and a sense of apprehension among CEOs, both globally and locally. The following are some interesting findings involving the Indian CEOs, as captured in this survey:

  • 38 percent observed that over the past 5 years alone, disruptive technological innovations have had a significant impact on competition within their respective industries.
  • 47 percent believe that in the next 5 years, disruptive technological innovations will have a significant impact on competition in their industry.
  • 77 are concerned about the speed of technological change.
  • 76 percent expressed concerns about rapidly changing customer behavior.
  • 77 percent mentioned the need to create differentiation in their products and offerings by managing data better. 

Its relevance in pharma:

The relevance of taking this wind of change in stride and embracing it fast, is beyond any reasonable doubt today. The 2017 report of EY, titled ‘Reinventing pharma sales and marketing through digital in India,’ also reaffirms: ‘Digital will play an ever-increasing role in this era of profound transformations, characterized by increasingly informed patients/physicians, new range of customers and new disruptive entrants. To stay relevant, pharma companies need to adopt a nimbler approach and make data the currency of marketing.’.”.

The urgency:

A sense of urgency for this change has also been epitomized in the same report, as it underscores that digital disruption has demolished 52 percent of Fortune 500 companies, since 2000. The study further reiterates: “The pace of transformation has increased, competition has intensified and business models have been profoundly disrupted. This shift is happening at breakneck speed across industries, and pharma can no longer be an exception. Customers have already embraced technological changes, through their many digital touch points, and pharma must look toward digital to re-imagine the customer experience.”

Just changing manual processes to digital won’t suffice:

This is exactly what is mostly happening today in pharma. Concerned employees, in general, are also receiving training inputs accordingly. Vindicating this point, a recent study reiterates that just changing manual processes to digital won’t suffice, any longer. Delivering greater value to the stakeholders continuously through digitization of business is the name of the game.

The above EY report unambiguously endorses that: “Whatever was being done manually earlier is now being done digitally. But we are not adding additional value.”

While capturing in the report Indian pharma’s journey to the digital world, it articulates, though some digitization initiatives are being taken now, Indian pharma companies are still way behind their global counterparts. The survey found 53 percent of the participating companies still at the ‘beginners’ stage, while 40 percent are at the ‘conservatives’ stage and only 7 percent have moved toward the ‘explorers’ stage.

Three fundamental non-technical barriers, and the way forward:

Two important studies – one by EY, as quoted above, flagged three fundamental non- technical barriers in this area, and the other one by McKinsey & Co that proposed three strategic actions for Indian pharma to start on a digital path by leveraging its intrinsic value, meaningfully.

EY study indicated, 86 percent of the senior pharma leaders exhibited a strong positive inclination toward digital as a ‘strategic’ rather than a tactical approach. It then highlighted the following three key barriers to embracing digital:

  • Lack of clear digital strategy for the organization
  • Incremental value proposition and effective delivery
  • Change management

McKinsey & Co in its August 2015 report, titled ‘The road to digital success in pharma’ also indicated, though differently, lack of a clear strategic direction and focus in this area. The study noted: ‘Most pharma companies have started to build some digital capabilities, but the talent and resources for their efforts can be fragmented, often across hundreds of small initiatives. Without clear strategic direction and strong senior sponsorship, digital initiatives often struggle to secure the funding and human resources required to reach a viable scale, and they cannot overcome barriers related to inflexible legacy IT systems.’

Based on the above finding, the paper proposed three strategic actions for pharma companies to place it on the right trajectory, capturing the differential value of digital, as follows:

  • Develop the right organization for new business models with significant value addition from digital. This, I reckon, would involve a cultural shift.
  • Focus on two or three flagship initiatives, such as building a digital ecosystem for patient adherence to a blockbuster drug.
  • Run collaborative experiments, and then scale what works, such as putting the right people from IT, business compliance, and outside partners in a ‘war room’ to run quick test-and-learn cycles of a well deliberated digital strategic initiative. Where results are positive, scale those up.

Personalization in every facet of the value delivery system:

As we move ahead, personalization in virtually every facet of the value delivery system is unlikely to remain optional for the Indian pharma players. With this wind of change gathering further momentum, many will eventually witness a mind-boggling level of personalization – spanning across from personalized diagnosis of serious ailments based on complex genomics, doctors’ writing personalized medicines to tech savvy pharmacists dispensing 3D printed individualized formulations.

This trend will continue evolving with an ascending trend of outcomes, breaking all conceivable barriers. Accordingly, services to patients and physicians would also demand more personalization, along with the other stakeholder engagement process.

Most of these may appear no more than a figment of imagination today, or probably a science fiction to many – just as what the incredible narrative of unleashing unfathomable potential of the Internet appeared to so many, not so long ago. Indian pharma players may prefer to wish away this emerging scenario, but at their own peril.

Conclusion:

The Indian pharma industry is currently passing through a phase of transition to move into the digitized world. Just doing digitally whatever is being done manually now or earlier, won’t suffice, any longer.

Giving shape to a robust, comprehensive digital strategic game plan for the organization, as a whole, is the need of the hour. Pharma CEOs would require leading their respective core teams to the drawing boards for charting out this digital pathway, without further delay.

This would be a game changer, as constantly delighting the stakeholders with the best possible value addition in business, emerges as the primary means for sustainable organizational excellence. Long term success in this effort, would call for constant upgradation of the state of the art digital platforms and tools.

This is sine qua non to pharma success in the digitized world – offering a strong foothold as the new paradigm ushers in. Envisioning, what all-round excellence in business would entail in a rapidly evolving digitized world, and championing its effective implementation on the ground, sooner, is now a critical accomplishment factor for pharma CEOs in India.

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.

Cancer Care: Dawns A New Era Of Precision Medicine In India

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The concept of ‘Precision Medicine’ has started gaining increasing importance, in the treatment process of many serious diseases, such as cancer. It is now happening in many countries of the world, including India.

The National Institutes of Health (NIH) of the United States, describes ‘Precision Medicine’ as:

“An emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.”

This is quite in contrast to the widely practiced “one-size-fits-all” type of drug treatment approach, where disease treatment and prevention strategies are developed for the average person, with less consideration for the differences between individuals.

It continues, irrespective of the fact that the same drug doesn’t always work exactly the same way for everyone. It can be difficult for a physician to predict, which patient will benefit from a medication and who won’t, besides having any advance inkling on who will experience Adverse Drug Reactions (ADR) with it, and who will not.

Whereas, the treatment path of ‘Precision Medicine’ allows doctors to predict more accurately which treatment and prevention strategies will work most effectively for a particular disease, and in which groups of people. This is mainly because, ‘Precision Medicine’ looks at the root cause of the ailment for each patient.

For example, in cancer care, use of the term ‘Precision Medicine’ would mean a treatment process for patients with similar tumors, that has been immaculately worked out in accordance with their unique genetic, physical, psychosocial, environmental, and lifestyle factors. Thus, especially for the treatment of life-threatening diseases, a gradual shift from “one-size-fits-all” types of medicines to ‘Precision Medicines”, could bring a new hope of longer survival or remission, for many such patients.

For example, in precision cancer care, it is all about analyzing a patient’s tumor to determine with specificity what drug or combination of drugs will work best with least side effects for that particular individual.

In this article, I shall focus on the development, use and benefits of ‘Precision Medicine’ in cancer, especially in India.

Not a radically new concept:

Several examples of ‘Precision Medicine’ can be found in a few other areas of medicine, as well, though its use in everyday health care is not very widespread, as on date.

One such example can be drawn from the blood transfusion area. A person requiring it, is not given blood from a randomly selected donor. To minimize the risk of any possible post-transfusion related complications, the blood for transfusion is selected only after scientific confirmation that the donor’s blood type matches to the recipient.

Difference between ‘Precision’ and ‘Personalized’ Medicines:

There is a significant overlap between these two terminologies. According to the National Research Council (NRC) of the United States, ‘Personalized Medicine’ is an older term having a meaning similar to ‘Precision medicine’, but may not always be exactly the same.

This change was necessitated as the term ‘Personalized’ could be interpreted to imply that treatments and preventions are being developed uniquely for each individual. Whereas, in ‘Precision Medicine’, the focus is on identifying which approaches will be effective for which patients based on genetic, environmental, and lifestyle factors, as stated above. The NRC, therefore, preferred the term ‘Precision Medicine’ to ‘Personalized Medicine’ to avoid such confusions or misunderstandings. Nevertheless, these two terms are still being used interchangeably.

Another terminology – ‘Pharmacogenomics’ is also used by some, in the same context, which is, in fact, a part of ‘Precision Medicine’. According to National Library of Medicine, United States, Pharmacogenomics is the study of how genes affect a person’s response to particular drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to variations in a person’s genes.

Global initiatives taking off:

Currently, in various parts of the world, there are many initiatives in this area. However, one singular state sponsored initiative, I reckon, is exemplary and stands out.

According to NIH, in early 2015, President Obama announced a research effort focusing on bringing ‘Precision Medicine’ to many aspects of health care. The President’s budget for fiscal year 2016 included US$216 million in funding for the initiative for the NIH, the National Cancer Institute (NCI) – the NIH institute focused on cancer research, and the Food and Drug Administration (FDA).

‘The Precision Medicine Initiative’ has both short-term and long-term goals:

  • The short-term goals involve expanding precision medicine in the area of cancer research. Researchers at the NCI hope to use this approach to find new, more effective treatments for various kinds of cancer based on increased knowledge of the genetics and biology of the disease.
  • The long-term goals focus on bringing ‘Precision Medicine’ to all areas of health and healthcare on a large scale.

The market:

According to a July 2016 research report by Global Market Insights, Inc., the ‘Precision Medicine’ market size was over US$39 billion in 2015, and has been estimated to grow at 10.5 percent CAGR from 2016 to 2023, expanding the market to US$ 87.79 billion by end 2023.

The demand for ‘Precision Medicine’ is expected to significantly increase, specifically in cancer treatments, and also would be driven by advancements in new healthcare technologies, and favorable government regulations, in this area.

Faster US regulatory approval:

According to an August 15, 2016 article, published in the ‘MedCity News’ – a leading online news source for the business of innovation in health care, companion diagnostics, this trend is gaining currency as novel drugs are being paired up with tests that determine which patients will have a higher chance of responding to that drug.

This is vindicated by an expert analysis of a recent study, which found that the probability of a drug approval jumped three-times to 25.9 percent of those drugs that were approved with a predictive biomarker, from 8.4 percent for drugs without one.  This means a threefold increase in success, as determined by FDA registration, if any pharma or biologic drug company had a predictive marker in its new product development strategy. This indication would expectedly encourage more drugs to come with companion diagnostics than without, as the analysis underscored.

The National Institutes of Health (NIH) of the United States defines ‘Biomarkers’ or ‘Biological Markers’ as, “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention.”

‘Precision Medicine’ in India:

In the Indian health care space, ‘Precision Medicine’ is still in its nascent stage. This is despite its need in the country being high, especially while treating life threatening ailments, such as cancer, with greater precision, predictability and, therefore, more effectively than at present.

In several focus group studies too, the local medical specialists have also concurred with the global estimation of the inherent potential of ‘Precision Medicine’, as it rapidly evolves in India, particularly for use in oncology.

Local research:

Studies related to ‘Precision Medicine’ have already commenced, though in a modest scale, in a number of Government research centers, such as, Centre for Cellular and Molecular Biology (CCMB), Indian Council of Medical Research (ICMR), National Institute of Biomedical Genomics (NIBMG) and Institute of Genomics & Integrative Biology (IGIB).

Some large Government Hospitals too, like, All India Institute of Medical Sciences (AIIMS), National Institute of Mental Health and Neurosciences (NIMHANS), and even in Tata Memorial Hospital are making good progress in this area.

Local potential and market impact:

In March 2016, a leading daily of India had reported with examples that oncologists have started using ‘Precision Medicine’, in the country.

In this report, a molecular geneticist was quoted saying, “We see patients with blood, breast, lung, and colon cancer being referred for genetic testing on a routine basis. This testing is either for predictive purposes or for precision medicine guidance, where genetic tests are increasingly being used to determine which drug may be used for treatment.”

“We have had more than a few cases where patients respond well after being put on a new drug based on the results of these tests,” the expert said.

According to a May 2016 report of the Indian Council of Medical Research (ICMR), in the year 2016, the total number of new cancer cases is expected to be around 14.5 lakh (1.5 million), and the figure is likely to reach nearly 17.3 lakh (1.7 million) of new cases in 2020.

Over 7.36 lakh (736,000) people are expected to succumb to this disease in 2016 while the figure is estimated to shoot up to 8.8 lakh (880,000) by 2020. The data also revealed that only 12.5 percent of patients come for treatment in early stages of the disease.

Taking note of this fast ascending trend, it would be quite reasonable to expect that treatment with ‘Precision Medicine’, using advanced genetic profiling, would catch up, and grow proportionally in some section of the population, sooner than later. This trend is expected to keep pace with the commensurate increase in the anti-cancer drug market of India.

In tandem, the demand for preventive measures, especially, for cancer, cardiovascular, psychosomatic and many chronic metabolic diseases at the onset or prior to even onset stages, based on genome-based diagnostics, are also expected to go north. This would primarily be driven by increasing health awareness of the younger generation of India.

The spin-off commercial benefits for the pharma and diagnostic players in India, competing in these segments, could well be a significant boost even in the market potential of the older generic drugs in new patient groups, prompted by many out-of- box diagnostic and disease treatment strategies.

Another interesting article on genomic diagnostics for ‘Precision Medicine’, published on March 15, 2016 by ‘Pistoia Alliance’ – a global, not-for-profit alliance in life science that aims at lowering barriers to innovation in R&D, also expressed similar views regarding the future potential of ‘Precision Medicine’ in India.

Some key strategic steps:

Taking proactively some key strategic steps for business planning and development by the domestic pharma and diagnostic players, is now more important than ever before. This may call for developing some critical studies that would accelerate working out novel strategies for ‘Precision Medicine’ in India, besides obtaining required regulatory approvals in the coming years. The studies may include, among others:

  • Detailed analysis of target patient populations
  • Their genetic makeup for different types, or sub-types of diseases
  • Addressable sub populations
  • Their current treatment strategies, costs, affordability and differentiated value offerings of each, if any.

Conclusion:

Genomic research in India is now mainly directed towards routine genome-based diagnostics for a number of conditions, mostly for cancer. The country needs to encourage taking rapid strides to first sharpen and then gradually broaden this area, in various ways, for more effective and predictable treatment outcomes with ‘Precision Medicine’. As on date, most of such studies are carried out in the United States and Europe.

Alongside, a robust regulatory framework is required to be put in place, for wider usage of ‘Precision Medicine’ in India, without causing any concern to stakeholders. Government should also explore the need of clearly defining, and putting in place transparent, patient-friendly and robust Intellectual Property (IP) policies in the ‘Precision Medicine’ related areas to encourage innovation.

Healthcare expenditure being out-of-pocket for a vast majority of the population in India, the additional cost to be incurred for genomic sequencing tests, still remains a huge concern for many. Nevertheless, the good news is, many players have now gradually started entering into this area, spurring a healthy competition. This process would also gain accelerated momentum, as we move on.

This is just a dawn of a new era of ‘Precision Medicine’ in India. Its rapid development, is expected to be driven by a large number of startups, equipped with state-of-art technology, and hopefully, with greater health insurance penetration and the support from the Government. All this would bring the ‘Precision Medicine’ treatment cost affordable to a sizeable section of the population in the country, particularly for the treatment of cancer. The evolving scenario appears to be a win-win one, both for the patients, as well as the pharma and diagnostic players in India.

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. 

Cancer Cure: Inching Towards The ‘Holy Grail’?

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In a Press Conference on August 20, 2015, the 39th President of the United States, now 90-year-old  Jimmy Carter, revealed (video) that during a liver surgery earlier this month the doctors diagnosed that he has cancer. The type of cancer that he is suffering from is called melanoma, which has already spread to his liver and brain. Medical jargon would term it as deadly metastatic cancer.

Though the surgeons have removed the liver tumor, and well-targeted radiation treatment for four other small tumors in his brain has already been initiated, the original site of the melanoma, the lethal skin cancer, has reportedly not been found, as yet.

Mr. Carter’s medical treatment has started with an infusion of a new class of drug that uses the human immune system to fight cancer cells. The drug has been reported to work not only in advanced metastatic cancer, but also in the old age of patients. The former American President appears optimistic about the treatment outcomes with this new therapy, ‘placing his fate in the hands of God’, though initially he thought that he had just weeks to live.

I shall deliberate in this article, in an easy to understand language, though briefly, the promises offered by two latest options for cancer cure. One of these two, has just become available to patients and the other one, after an initial jaw-dropping success, is undergoing further tests in a renowned research laboratory of the United States.

Two novel pathways for cancer treatment:

Until recently, surgery, radiation and chemotherapy used to be the three common options for cancer treatment. One breakthrough option has just been launched and more in the offing.

In search of a cure for cancer, pathbreaking outcomes of medical research, especially in the following two areas, are significant:

A. Immunotherapy: It is a revolutionary approach to cancer treatment. The first of this novel class of drugs has just come to the market, with which Mr.Jimmy Carter is now reportedly being treated.

B. Re-programming cancer cells back to normal: Success has just been achieved in laboratory studies with this technique. It holds a strong promise to cure cancer, universally.

A. Immunotherapy:

On June 1, 2015, in an article titled, ‘Cure for terminal cancer’ found in game-changing drugs, “The Telegraph” – well-regarded international news daily, reported on anti-cancer immunotherapy drugs, as follows:

“Terminally ill cancer patients have been ‘effectively cured’ by a game-changing new class of drugs. In one trial, more than half of patients who had just months to live saw deadly tumors shrink or completely disappear.”

“In recent days, the results of trials of a number of treatments which harness the body’s immune system have been announced at the American Society of Clinical Oncology’s annual conference in Chicago. They show promise in the fight against skin cancer and lung disease.”

As we know, most of the cancers are deadly. All these grow and spread, as they manage to hide from the immune system, disguising the life-threatening danger. Thus, medical research scientists pondered that the human immune system could play a critical role in the fight against cancer and even cure, by harnessing its ability to fight the deadly disease, effectively and decisively.

To achieve this goal, this class of new cancer drugs work by allowing the body to recognize and attack cancer as any other harmful invader to the body. It effectively blocks a cellular pathway that hinders the ability of the human immune system to attack cancer cells.

At present, to treat different types of cancer, more number of immunotherapy drugs are undergoing clinical investigations.

Brilliant treatment outcomes, but not universal:

It has been reported, about one third of patients taking immunotherapy for the treatment of cancer experienced positive results. Those who responded to this therapy, showed immediate effect with their tumors shrinking or vanishing in a matter of weeks. As a result, the patients who had no more than weeks or months to live, just as former US President Jimmy Carter, have gone into remission for years and continuing with their normal lives.

It has also been reported, otherwise such patients could expect to live just nine months, if given standard treatment of cancer. Researchers said, they were hopeful that half of the patients responded to immunotherapy would end up “living disease-free”.

These drugs are expensive, costing roughly US$150,000 per year, which is a part of a different debate altogether.

Not a ‘magic bullet’:

Besides its high cost and outstanding quality of results, it is worth noting that immunotherapy is not a ‘magic bullet’ for all types of patients and in all cancer. It, therefore, throws a challenge for the oncologists to understand, why immunotherapy benefits only to some cancer patients, and who are those patients?

Moreover, there is a possibility of immunotherapy sending immune system of some patients to overdrive, precipitating auto-immune disorder that may attack also the healthy cells.

Thus, immunotherapy is not the ‘Holy Grail’ for the treatment of cancer, neither it is nowhere near a perfect drug for the treatment of all types of cancers in all patients.

Two key findings:

In this regard, two key findings of the researchers on immunotherapy are as follows:

  • Roughly around 15 to 20 percent of patients could experience shrinkage or remission of cancer
  • Half of the patients who responded found it lasting for at least six months

Thus, immunotherapy can at best be a cure for only some terminally ill cancer patients, mostly for some time, but not for all.

“In the hands of God”:

All these factors on immunotherapy probably would help us to understand, why an erudite person like Mr. Jimmy Carter said, though optimistic about the new treatment, he is placing his fate ‘in the hands of God’.

B. Re-programming cancer cells back to normal: 

The question, therefore, comes up now, if immunotherapy is not the ‘Holy Grail’ for cancer treatment that the research scientists have been intensively searching for, is there anything else coming up for cancer cure?

It appears so. A totally different approach to re-program the cancer cells back to normal has very recently been reported by Mayo Clinic’s Florida Campus in the United States. With this, cancer researchers’ dream of making the tumor cells morphing back to normal cells, they once were, would probably come true.

The research findings, published in Nature Cell Biology on August 24, 2015, represents ‘an unexpected new biology that provides the code, the software for turning off cancer,’ said the senior investigator of this study.

In the normal process, cells in the human body divide constantly to replace themselves and stop dividing when they have replicated sufficiently. However, unlike the normal cells, cancer cells do not stop dividing, they go out of control, leading to huge cell reproduction and tumor growth.

For the ultimate cure of cancer, scientists at Mayo Clinic have now reportedly succeeded in reversing the process responsible for the normal cells from replicating too quickly.

Possible cure now within sight?

This could ultimately lead to a newer class of breakthrough treatment that would be able to reverse cancerous growth in the human body, possibly curing cancer, without the need of surgery, chemotherapy, radiation or even immunotherapy.

Scientists at the Mayo Clinic have said that their initial experiments in some aggressive types of cancer are quite encouraging. They have successfully done this in very aggressive human cell lines from breast and bladder cancer.

Towards the ‘Holy Grail’:

In pursuit of finding a cancer cure, research scientists have been making commendable progress, over a period of time.

In the last few years, spectacular breakthroughs in treatment of cancer have been possible from the increasing genetic and biological understanding of the researchers, especially in ascertaining exact defects in the DNA code of human genes that cause cancer.

Ability to sequencing human genome has offered a key tool to the researchers to compare the DNA codes of cancerous and normal cells and identify the differences.

From within the 20,000 human genes, around 500 cancer genes have been reportedly discovered and are being catalogued. Clear understanding of what happens precisely when the cells divide uncontrollably and cancer spreads in different parts of the patients’ body, is taking place with commendable progress of various research initiatives in this area.

Based on the current knowledge on human genome, a number of new drugs have been and are being developed to target the cancer-causing genes with great accuracy. Such types of drugs are called ‘personalized medicines’, as these act on specific gene abnormality of patients related to certain types of cancer. Sophisticated laboratory tests facilitate treatment with ‘personalized medicines’. These are more effective with lesser side-effects, as compared to generally used anti-cancer drugs, prescribed to all cancer patients.

However, the question keeps lingering, ‘Is the Holy Grail for cancer cure has now come within sight?’

Conclusion:

Medical scientists continue to take rapid strides towards better and more effective treatment for cancer, if not cure, with fewer side-effects.

Claims for long remissions with immunotherapy, are being reported for some patients with even metastatic cancer and also in old age, just like former President of America – Mr. Jimmy Carter.

The success achieved by the scientists of ‘Mayo Clinic’ in re-programming rogue cancer cells back to normal, is stunning.

Being successful in this effort, the researchers have compared cancer with a complex software program of life. When it goes out of control, ‘instead of the code for normal cells, a code for making abnormal cells is executed’. This new study signals a strong possibility of bringing the cancer cells back to normal.

Medical experts keep their fingers crossed. Although, some of them do apprehend that there may never be a single ‘Magic Bullet’ to cure all types of cancer in all patients. This is mainly because cancer involves a large number of different disease areas, such as, breast, lung, bowel, prostate, blood and so on.

But hope refuses to fade out, as science continues to keep unravelling spectacular breakthroughs in this direction, at a fairly brisk pace. All these researches may be cancer types or patient types specifics, but the progress is taking place in the right direction.

Even in the ‘Mayo Clinic study’, scientists have been, so far, successful in re-programming the breast and bladder cancer cells back to normal, though they believe that this success sends a strong signal of an “early and somewhat universal event in cancer.”

Immunotherapy is undoubtedly a path breaking step that ensures cure in some types of cancer and in some categories of patients. However, if re-programming the cancer cells back to normal, eventually becomes an ‘universal event’ in the treatment of this generally frightening disease, no doubt, the medical science is now slowly but surely inching towards the ‘Holy Grail’ for cancer cure…at long last.

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.

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.

The R&D Factor: “One of the Great Myths of the Industry”

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Yes, that is what the global CEO of one of the Pharmaceutical giants of the world commented in a very recent interview with Reuters. Adding further to this comment he said, “US $1 billion price tag for R&D was an average figure that includes money spent on drugs that ultimately fail… If you stop failing so often, you massively reduce the cost of drug development  … It’s entirely achievable.”

Therefore, he concluded his interview by saying that the pharmaceutical industry should be able to charge much less for new drugs by passing on efficiencies in R&D to the customers.

A vindication:

The above comment does not seem to be a one off remark. A recent study on R&D productivity of 12 top pharmaceutical companies of the world by Deloitte and Thomson Reuters highlighted that the average cost of developing a new medicine is now US$ 1.1 billion with the most successful company in the group studied incurred an average cost of just US$ 315 million, while at the other extreme, another company spent US$ 2.8 billion.

How much of it then covers the cost of failures and who pays for such inefficiencies?

Some experts have gone even further:

Some experts in this area have gone even further arguing that pharmaceutical R&D expenses are over stated and the real costs are much less.

An article titled “Demythologizing the high costs of pharmaceutical research”, published by the London School of Economics and Political Science in 2011 indicates that the total cost from the discovery and development stages of a new drug to its market launch was around US$ 802 million in the year 2000. This was worked out in 2003 by the ‘Tuft Center for the Study of Drug Development’ in Boston, USA.

However, in 2006 this figure increased by 64 per cent to US$ 1.32 billion, as reported by a large overseas pharmaceutical industry association.

The authors of the above article also mentioned that the following factors were not considered while working out the 2006 figure of US$ 1.32 billion:

▪    The tax exemptions that the companies avail for investing in R&D.

▪   Tax write-offs amount to taxpayers’ contributing almost 40% of the R&D cost.

▪   The cost of basic research should not have been included, as these are mostly         undertaken by public funded universities or laboratories.

The article commented that ‘half the R&D costs are inflated estimates of profits that companies could have made if they had invested in the stock market instead of R&D and include exaggerated expenses on clinical trials’.

“High R&D costs have been the industry’s excuses for charging high prices”:

In the same article the authors strongly commented as follows:

“Pharmaceutical companies have a strong vested interest in maximizing figures for R&D as high research and development costs have been the industry’s excuse for charging high prices. It has also helped generating political capital worth billions in tax concessions and price protection in the form of increasing patent terms and extending data exclusivity.”

The study concludes by highlighting that “the real R&D cost for a drug borne by a pharmaceutical company is probably about US$ 60 million.”

 Another perspective to the “R&D Factor”:

A book titled “Pharmaceutical R&D: Costs, Risks, and Rewards”, published by the government of USA gives another perspective to the “R&D Factor”. It articulates that the three most important components of R&D investments are:

  • Money
  • Time
  • Risk

Money is just one component of investment, along with a long duration of time, to reap benefits of success, which is intertwined with a very high risk of failure. The investors in the pharmaceutical R&D projects not only take into account how much investment is required for the project against expected financial returns, but also the timing of inflow and outflow of fund with associated risks.  It is thus quite understandable that longer is the wait for the investors to get their real return, greater will be their expectations for the same.

This publication also highlights that the cost of bringing a new drug from ‘mind to market’ depends on the quality and sophistication of science and technology involved in a particular R&D process together with associated investment requirements for the same.

In addition, regulatory demand to get marketing approval of a complex molecule for various serious disease types is also getting more and more stringent, significantly increasing their cost of clinical development in tandem. All these factors when taken together, the authors argue, make the cost of R&D not only very high, but unpredictable too.

Thus to summarize from the above study, high pharmaceutical R&D costs involve:

  • Sophisticated science and technology dependent high up-front financial investments
  • A long and indefinite period of negative cash flow
  • High tangible and intangible costs for acquiring technology with rapid trend of obsolescence
  • High risk of failure at any stage of product development

Even reengineered R&D model may not be sustainable:

Many research scientists have already highlighted that sharp focus in some critical areas may help containing the R&D expenditure to a considerable extent and also would help avoiding the cost of failures significantly. The savings thus made, in turn, can fund a larger number of R&D projects.

The areas identified are as follows:

  • Early stage identification of unviable new molecules and jettisoning them quickly.
  • Newer cost efficient R&D models.
  • Significant reduction in drug development time. 

Unfortunately, sustainability of the above model too still remains in the realm of a wishful thinking and raises a serious question mark to many for various other reasons.

Should Pharmaceutical R&D move away from its traditional models?

Thus the critical point to ponder today, should the Pharmaceutical R&D now move from its traditional comfort zone of expensive one company initiative to a much less charted frontier of sharing drug discovery involving many players? If this overall approach gains acceptance sooner by all concerned, it could lead to increase in R&D productivity significantly at a much lesser cost, benefiting the patients community at large.

Finding right pathway in this direction is more important today than ever before, as the R&D productivity of the global pharmaceutical industry, in general, keeps going south and that too at a faster pace, prompting major cuts in the absolute R&D expenditure by many, as compared to the previous year.

A global R&D spend comparison (2011 and 12):

R&D expenditures in absolute terms of the following global companies in 2011 and 2012, without drawing any relationship to their respective R&D productivity, were reportedly as follows:

Company

2012

US$ Bn.

2011

US$ Bn.

% Change

% of Sale
Roche

10.10

8.81

13.7

21.0
Novartis

9.33

9.58

(3.0)

16.4
Merck

8.16

8.46

(4.0)

17.0
Pfizer

7.90

9.10

(13.0)

13.3
J&J

7.66

7.54

1.5

11.6
Sanofi

6.40

6.24

2.5

14.1
GSK

5.95

6.01

(1.0)

15.0
Eli Lilly

5.30

5.00

5.0

23.4
AstraZeneca

5.24

5.52

(5.0)

18.8
Abbott Labs

4.32

4.12

4.7

10.8
Total

70.36

70.38

 

 

Source: Fierce Biotech, March 18, 2013

This particular table points out that five out of the reported ten companies had to spend less towards R&D in 2012 as compared to 2011 and four out of the remaining five players were able to increase their R&D spend just marginally.

Thus the same question comes at the top of mind yet again: is the current pharmaceutical R&D model sustainable and working with optimal productivity and cost efficiency for  the benefits of patients?

Towards greater sustainability of the R&D model: 

A July 2010 study of Frost & Sullivan reports, “Open source innovation increasingly being used to promote innovation in the drug discovery process and boost bottom-line”.

It underscores the urgent need for the global pharmaceutical companies to respond to the challenges of high cost and low productivity in their respective R&D initiatives, in general.

The ‘Open Innovation’ model assumes even greater importance today, as we have noted above, to avoid  huge costs of R&D failures, which are eventually passed on to the patients through the drug pricing mechanism.

‘Open Innovation’ model, as they proposed, will be most appropriate to even promote highly innovative approaches in the drug discovery process bringing many brilliant scientific minds together from across the world.

The key objective of ‘Open Innovation’ in pharmaceuticals is, therefore, to encourage drug discovery initiatives at a much lesser cost, especially for non-infectious chronic diseases or the dreaded ailments like Cancer, Parkinson’s, Alzheimer, Multiple Sclerosis, including many neglected diseases of the developing countries, making innovative drugs affordable even to the marginalized section of the society.  

“Open Innovation” is very successful in IT industry:

The concept of ‘Open Innovation’ is being quite successfully used in the Information Technology (IT) industry since nearly three decades across the world, including India. Web Technology, Linux Operating System (OS) and even the modern day ‘Android’ are excellent examples of commercially successful ‘Open innovation’ model in IT,

In the sphere of Biotechnology ‘Human Genome Sequencing’ is another remarkable outcome of such type of R&D model. Therefore, why not a similar model be actively pursued in a much larger scale to discover newer and innovative drugs at a much lesser cost for greater access to patients?

Issues involved:

In the evolving process of ‘Open Innovation’ in pharma there are some issues to be addressed and at the same time some loose knots to be tightened to make the process increasingly more user friendly and robust. Many experts feel that the key issues for the ‘Open Innovation’ model are as follows:

▪   Who will fund the project and how much?

▪   Who will lead the project?

▪   Who will coordinate the project and find talents?

▪   Who will take it through clinical development and regulatory approval process?

That said, all these issues do not seem to be insurmountable problems at all to add greater speed and efficiency to the process, as the saying goes, ‘where there is a will, there is a way’.

Conclusion: 

Having deliberated on this issue as above, I reckon, there is a dire need to make the process of offering innovative drugs at affordable prices to the patients sustainable over a long period of time, for the sake of all.

This can happen only when there will be a desire to step into the uncharted frontier, coming out of much beaten and a high cost tract of R&D, especially after having picked-up the low hanging fruits. Dove tailing the passion for business excellence with the patients’ interest, dispassionately, will then be the name of the game.

As the Reuters article quoting the CEO of a global pharma major points out, in addition to improvements in research, increasing global demand for medicines and the explosion in the volume of products sold in emerging markets should also contribute to lower unit costs of the innovative drugs ensuring their greater access to patients.

This process, in turn, will help fostering a win-win situation for all stakeholders, exploding “one of the great myths of the industry” – The ‘R&D Factor’.

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.

 

 

 

A Disruptive Innovation in Healthcare – Personalized Medicines

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Tufts Center for the Study of Drug Development (Tufts University) in its publication named ‘Impact Report’, November/December 2010 articulated, “Biopharmaceutical companies are committed to researching and developing personalized medicines and within their development pipelines, 12%-50% of compounds are personalized medicines.”

Thus the disruptive innovation process towards ‘Personalized Medicines’ have already begun. Over a period of time ‘Personalized Medicines’ will be targeted to the biological/genomic profile of an individual to significantly improve the quality of healthcare to the patients.

This paradigm shift in the healthcare space would prompt similar changes in various disease diagnostic technologies, which will not only be able to detect a disease well before the appearance of symptoms, but would also  indicate which patients will best respond to or be adversely affected by which medications.

‘Personalized Medicines’ will in that process ensure a critical shift from the disease oriented treatment to a patient oriented treatment, which can be initiated much before the clinical manifestations of a disease are detected.

The technological march towards this direction is indeed risky and arduous one. However, the benefits that the humanity will accrue out of this disruptive innovation will far outweigh the risks in all forms.

Personalized Medicines:

Rapid strides in pharmacogenomics bring in a promise of radically different ways of treating diseases, as major pharmaceutical companies of the world make progress in developing much more effective medicines designed to target smaller populations.

The above ‘Impact Report’ defines Personalized Medicines as:

“Tailoring of medical treatment and delivery of health care to the 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.”

‘Personalized Medicines’ are expected to be an effective alternative to quite unwieldy current ‘blockbuster drugs’ business model.

What is then the aim of ‘Personalized Medicines’?
The aim of ‘personalized medicines’ 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, very shortly.

Some interesting recent developments:

  1. The Economist, March 12-18, 2011 in its article titled “Toward the 15-minute genome” reported that ‘nanopore sequencing’ of human genome is now gaining momentum. This could make sequencing of entire genomes of cancerous and healthy cells possible to accurately point out what has exactly changed in individual patients, enabling the oncologists to determine patient specific drugs for best possible results in each case, separately.
  2. New cancer marker has been reported to aid earlier detection of the disease, where repetitive stretches of RNA are found in high concentrations in cancer cells.
  3. A new blood test will accurately detect early cancer of all types with an accuracy of greater than 95%, when repeated the accuracy will even be even greater than 99%.
  4. ‘Breast On A Chip’ will test nano-medical detection and treatment options for breast cancer
  5. A brain scan will detect the telltale “amyloid plaques,” the protein fragments that accumulate between nerves in Alzheimer’s disease

In what way ‘Personalized Medicines’ will be different?

With ‘Personalized Medicines’ 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 such drugs.
These are expected to offer more targeted and effective treatment with safer drugs, and presumably at a lesser cost. Such medicines will also help identify individuals prone to serious ailments like, diabetes, cardiovascular diseases and cancer and help physicians to take appropriate preventive measures, simultaneously. ‘Personalized medicines’ in that process will focus on what makes each patient so unique, instead of going by the generalities of a disease.
To give a 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.
‘Personalized medicines’, therefore, have the potential to bring in a revolutionary change the way patients are offered treatment by the medical profession. Genomic research will enable physicians to use a patient’s genetic code to arrive at how each patient will respond to different types of treatments.
In the field of cancer, genetic tests are currently being done by many oncologists to determine which patients will be benefitted most, say by Herceptin, in the treatment of breast cancer.
Expected benefits from ‘Personalized Medicines’:

The expected benefits from the ‘Personalized Medicines’, 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 Health care: ‘Personalized Medicines’ will enable the physicians to prescribe ‘the right dose of the right medicine the first time for everyone’. This would give rise to much better overall healthcare.
Role of Pharmaceutical and Biotech companies:
Many research based pharmaceutical and biotechnology companies have taken a leading role towards development of ‘personalized medicines’ in line with their key role as healthcare enterprises. India is also taking keen interest in this science.
Some important issues:
However, there are some ethical and social issues in the development of ‘personalized medicines’ primarily in the area of genetic testing and consideration of race in the development of such medicines, which need to be effectively addressed, sooner.
Can it replace the ‘Blockbuster Drugs’ business model?
Realization of deficiencies in the economics of ‘block buster drugs’ R&D business model has made ‘personalized medicines’ a reality today.
Better efficacy and safety profile of ‘personalized medicines’ will prove to be cost-effective in the overall healthcare systems. Smaller and exclusive markets for ‘personalized medicines’ are also expected to be quite profitable for the pharmaceutical companies. However, such smaller segmentation of the market may not leave enough space for the conventional ‘blockbuster model’, which is the prime mover of the global pharmaceutical industry, even today.
Reports indicate that some renowned global pharmaceutical companies like, Roche, AstraZeneca, GlaxoSmithKline are making good progress towards this direction through collaborative initiatives.
Approximate cost of ‘Genome Sequencing’:
When human genome was first sequenced, the reported cost was staggering U.S$ 3 billion. However, with the advancement of technology, it came down to U.S$ 1 million, last year. Currently, the cost has further come down to U.S$ 60,000. With the rapid stride made in the field of biotechnology, combined with the economies of scale, cost of such genetic tests is expected to be around U.S$ 1,000 in near future, making it possible for people to obtain the blue print of their genetic code.
Savings on cost of Clinical trials with ‘Personalized Medicines’:
Genome sequencing will help identifying a patient population, which will be far more likely to respond positively to the new treatment. In that process, if it reduces costs of clinical trial by even 5%, expected net savings for the industry towards clinical trial have been reported to be around U.S$ 5 billion.
With ‘personalized medicines’ the innovator companies will be able to significantly reduce both time, costs and the risks involved in obtaining regulatory approvals and penetrating new markets with simultaneous development of necessary diagnostic tests. Such tests will be able to identify patients group who will not only be most likely to be benefitted from such medicines, but also will be least likely to suffer from adverse drug reactions.
Therefore, considerable cost advantages coupled with much lesser risks of failure and significant reduction in the lead time for clinical trials are expected to make ‘personalized medicines’ much more cost effective, compared to conventional ‘blockbuster drugs’.
Innovative and cost effective way to market ‘Personalized Medicines’:
With ‘personalized medicines’ the ball game of marketing pharmaceuticals is expected to undergo a paradigm shift. Roche’s model of combining necessary diagnostic tests with new drugs will play a very important role in the new paradigm.
Roche is ensuring that with accompanying required diagnostic tests, the new oncology products developed at Genentech can be precisely matched to patients.
Can ‘Personalized Medicines’ be used in ‘Primary Care’ also?
To use ‘personalized medicines’ in a ‘primary care’ situation, currently there is no successful model. However, it has been reported that in states like, Wisconsin in the U.S, initiative to integrate genomic medicines with ‘primary care’ has already been undertaken. Scaling-up operations of such pilot projects will give a big boost to revolutionize the use of ‘personalized medicines’ for precision and targeted treatment of the ailing population.

Conclusion:

In my view, there does not seem to be any possibility of looking back now. The robust business model of ‘personalized medicines’, will now be the way forward, as much to the industry as to the patients. It is a win-win game.

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.