Dawns A New Era: Regenerative Medicine For Degenerative Disease

Posted on July 17, 2017 by Tapan Ray

Could breakthrough innovation in ‘Regenerative Medicine’ significantly reduce the need of expensive lifelong medications, or even make the use of some important medical devices less relevant, or even help avoiding expensive and risky surgical interventions? The common answer to these critical questions is now getting clearer, in tandem with the rapid progress of the science of ‘Regenerative Medicine.’

On June 13, 2017, Nature Biomedical Engineering published an interesting an article titled, “3D-printed vascular networks direct therapeutic angiogenesis in ischemia.” In simple words, these 3D-Printed patches are going to usher in a highly innovative way to treat ischemic diseases, in the future. As the researchers highlighted, arterial bypass grafts are currently considered as the gold standard for the treatment of end-stage ischemic disease, though many patients are unable to tolerate the cardiovascular stress of arterial surgery. The researchers found that implantation of 3D-printed grafts containing endothelial-cell-lined lumens, induces spontaneous and geometrically guided generation of collateral circulation in ischemic settings.

In rodent models of hind limb ischemia and myocardial infarction, these scientists successfully demonstrated that the vascular patches rescue perfusion of distal tissues, preventing capillary loss, muscle atrophy and loss of function.

In this article, I shall deliberate on the importance of this discovery, and its overall future implications on a broader perspective.

Regenerative medicine:

Here comes the basic question – What is ‘Regenerative Medicine’?

It is defined as a highly innovative branch of medicine that develops implementable methods to regrow, repair or replace damaged or diseased cells, organs or tissues. According to RegerativeMedicine.net following are illustrations of some conditions or diseases that regenerative medicine has the potential to cure, and what their current state of treatment looks like in in the American perspective:

Heart valves- 250,000 patients receive heart valves, at a cost of US$27 billion annually
Heart disease and Stroke- 950,00 people die of heart disease or stroke, at a cost of US$ 351 billion annually
Diabetes- 17 million patients have diabetes, at a cost of US$ 132 billion annually

I discussed in this blog, the subject of ‘3D Printing in health care’ on January 11, 2016. Hence, won’t dwell on that subject here

Ischemia, and the relevance of the above discovery:

Ischemia, as many would know, is a condition that restricts adequate flow of blood in some parts of our body, which over a period, may narrow, harden or even block the important blood vessels, much often resulting in stroke, heart attack or other related life-threatening vascular disorders.

Currently, ischemic heart conditions are usually treated either with blood thinning drugs, or blood vessel relaxants. In more serious stages of this condition, doctors prefer angioplasty or other surgical interventions, such as coronary artery bypass.

In this broad perspective, the relevance of the above discovery in addressing various debilitating or life- threatening ischemic conditions, is profound. Its novelty lies in the ability of the scientists making a 3D-printed patch that can be infused with cells to help grow healthy new blood vessels.

An emerging medical space:

The science of ‘Regenerative Medicine’ is increasingly being considered as an emerging medical space aimed at the treatment of those diseases that are usually classified as degenerative, incurable and irreversible. As it appears today, this science has the potential to unfold a new paradigm in this space, where patients can expect cure for many serious ailments, such as, spinal injuries, heart disease, Parkinson’s, Alzheimer’s disease and even diabetes, besides many others.

One more recent pursuit in this much uncharted frontier was reported in the British news daily – ‘The Telegraph’ on February 21, 2017, revealing the outcome of a path-breaking medical study for freezing the progression of a crippling ailment called Multiple Sclerosis (MS). This research followed a unique Stem Cell (SC) transplantation process, and is regarded as the largest long-term follow-up of SC transplantation treatment study of MS in regenerative medicine.

This study, spearheaded by Imperial College London, established that 46 per cent of patients who underwent the treatment did not suffer a worsening of their condition for five years. The process works by destroying the immune cells responsible for attacking the nervous system. This is indeed a very significant development in the space of medical research.

The treatment, called autologous hematopoietic stem cell transplantation (AHSCT), was given to patients with advanced forms of MS who had failed to respond to other medications. However, the researchers noted that the nature of the treatment, which involves aggressive chemotherapy, carried “significant risks”.

As many would know, MS is caused by the immune system malfunctioning and mistakenly attacking nerve cells in the brain and spinal cord, leading to problems with movement, vision, balance and speech. It’s a lifelong condition and often causes serious disability, with no cure still in sight. The disease is most commonly diagnosed in people in their 20s and 30s, although it can develop at any age.

A potential game changer:

According to California Institute for Regenerative Medicine (CIRM), this procedure has a game changing potential for successful use:

To replace neurons damaged by spinal cord injury, stroke, Alzheimer’s disease, Parkinson’s disease or other neurological problems

To produce insulin that could treat people with diabetes, and heart muscle cells that could repair damage after a heart attack, or

To replace virtually any tissue or organ that is injured or diseased

Research on “Regenerative Medicine’ signals a new hope:

Following are examples of just a few more promising developments, indicating that research in ‘Regenerative Medicine’ is taking rapid strides, signaling a new hope:

- A cure for Type 1 diabetes:

According to an international report on October 9, 2014, for the first time after 23 years of research, Harvard University has been able to manufacture millions of beta cells required for transplantation. It could mean a cure for diabetes, and the end of daily insulin injections for patients living with Type 1 diabetes. Although, just around 10 per cent of all diabetes is Type 1, it is the most common type of childhood diabetes.

The report indicated, the stem cell-derived beta cells are presently undergoing trials in animal models, including non-human primates, where they are still producing insulin after several months.

Another report of April 2014 indicates that for the first time, scientists have successfully replaced the damaged DNA of a type 1 diabetes sufferer with the healthy genetic material of an infant donor. When these cells are injected back into the diabetic patient, it is expected that they will begin to produce insulin on their own.

- Restoring vision in macular degeneration:

Yet another study published in ‘The Lancet’ in October 2014 stated that scientists in the United States have announced that single transplant of stem cells has helped restore the sight of patients suffering from incurable forms of blindness due to Age-related Macular Degeneration (AMD). Currently no effective treatments exist for this eye disorder, which can cause complete blindness due to the loss of light-receiving photoreceptor cells in the retina.

To recreate a type of cell in the retina that supports those photoreceptors, the new treatment uses stem cells derived from embryos that are only a few days old and have the ability to develop into any kind of tissue in the body. However, the transplants have proved controversial because they use stem cells derived from spare human embryos left over from IVF treatment.

- A cure for heart failure:

One more international report of May 01, 2014 states, by injecting human stem cells into the organs of macaque monkeys, scientists have been able to regenerate their damaged hearts by up to 40 per cent in just a few weeks. Thus, it appears now that a cure for heart failure could be just a few years away and would mean that even people who are “bed-bound” with heart failure could be “up and about” again within a few weeks.

As on date, the heart muscle cannot be repaired, making people with severe heart failure necessarily wait for a heart transplant, provided the patients are willing, and can afford so.

Conclusion:

There is a host of diseases, including several chronic ailments, such as diabetes, heart conditions, rheumatoid arthritis, or some types of cancer, which can’t be reversed, however, could be managed with a lifelong treatment. For most of these diseases, ‘Regenerative Medicine’ has the potential to be a game changer by transforming many lives.

Moreover, ‘Regenerative Medicine’ is expected not just to bring down the cost of health care and the disease burden significantly, but would also help increasing the economic productivity of a nation considerably.

Currently, medical research of the highest order in this area, has mostly been conducted by various academia of global repute, along with a few in the industry. It should soon involve, besides patients, several industries, including pharmaceuticals and biotech sectors, in a big way.

Nevertheless, this emerging trend sends a clear signal that to treat various chronic, incurable, irreversible and seriously debilitating degenerative diseases ‘Regenerative Medicine’ is now poised to take a giant leap in the health care space. In that process, it would possibly help healing various ailments in a more meaningful, providing a cure for many chronic diseases that was a badly missing piece in the medical science, so far.

Thus, ‘Regenerative Medicines’ to treat many ‘Degenerative Diseases’ signal a great potential to give an altogether new shape and dimension to the future of global health care. It is also expected to ensure lesser lifelong usage of expensive drugs, setting a new normal to bring back the patients’ lives back to the pre-disease state.

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.

Could Vaccine Prevent Heart Attacks?

Posted on July 10, 2017 by Tapan Ray

Could Vaccine Prevent Even Heart Attacks? The question may sound weird to many, but it really appears so, possibly reducing further need of several expensive medications for lifelong use. A good number of academic institutions, besides some biotechnology companies, are taking rapid strides in the newer areas of vaccine development to protect people from various non-infectious serious ailments, including some fatal disorders, such as heart attacks.

In this article, I shall deliberate on this area.

Picking up the thread:

One of the critically important preventive therapy to save millions of precious lives is – vaccination. Way back in 1796, Edward Anthony Jenner not only discovered the process of vaccination, but also developed the world’s first smallpox vaccine to save mankind from this highly infectious and life-threatening disease. As per published data, prior to this discovery, the mortality rate for smallpox was as high as up to 35 percent.

Very appropriately, Jenner is often referred to as the “Father of Immunology”, whose pioneering work has saved more lives than the work of any other person, in that era. Later, in 1901 Emil Von Behring received the first Nobel Prize (ever) for discovering Diphtheria serum therapy for yet another highly infectious disease, affecting mostly infants and children.

Nevertheless, the pioneering work of Edward Anthony Jenner laid the primary substructure of immunology, which continued to be developed as a robust prophylactic measure against various types of, initially infectious and communicable diseases.

Expanded scope for vaccines:

Gradually, the global focus of vaccine development started expanding from prophylactic vaccination for communicable disease such as smallpox, diphtheria, malaria and pneumonia; to non-infectious disorders, like cancer, diabetes and atherosclerosis that often leads to heart attacks and strokes; including several therapeutic vaccines, especially for cancer. The list continues.

In other words, from inducing long-life immunity against exogenous or foreign antigens in infectious diseases caused by microorganisms, to inducing similar immune reaction against the body’s own molecules, which are responsible for precipitating seriously debilitating or life-threatening pathological changes. These include conditions, such as cardiovascular or metabolic disorders and many other chronic ailments, including various types of the deadly disease – cancer.

Would vaccines prevent even heart attacks?

Let me now get back to where I started from: Would vaccines prevent even heart attacks?

Medical experts often say, until a sudden heart attack occurs, patients with atherosclerosis may show no symptoms for decades. This epitomizes the seriousness of this disorder in human population.

Since long, atherosclerosis used to be considered as ‘a lipid-driven disease caused by the continuous accumulation of cholesterol in the arterial intima.’ However, that concept is changing now based on enough scientific evidences. These clearly indicate that ‘atherosclerosis is predominately a chronic low-grade inflammatory disease of the vessel wall with an interplay of humoral, cellular, and locally produced pro-inflammatory factors.’

Atherosclerosis is a chronic low-grade inflammatory disease:

In the above context, a recent research study has arrested the attention of many medical scientists, including several top cardiologists, across the world. This article, published on June 19, 2017, in the peer-reviewed European Heart Journal reported the development of a vaccine that induces an effective immune response in mice to significantly reduce plasma lipids, systemic and vascular inflammation, and atherosclerosis lesions in the aorta.

Leverages the immune system of the body:

In simple words, this cholesterol-lowering vaccine demonstrates how the immune system of the body can be leveraged to lower blood lipids, signaling a strong potential to make drugs, such as statins, possibly irrelevant.

This is the first intervention study based on a well-established, translational mouse model for hyperlipidemia and atherosclerosis. The research found, as compared with the control group, the vaccine reduced total and LDL cholesterol levels in the mice, as well as reduced signs of fatty build-up in the arteries.

Potentially an effective and economical approach:

The authors believe, the vaccine may represent an effective and economical approach, with higher patient compliance, in the treatment and prevention of similar cardiovascular pathologies. Taking the study to its next stage, they have already enrolled human volunteers to conduct the phase one study, for a detailed scientific assessment on how this vaccine will work for the patients suffering from similar disorders.

Another interesting development:

To give just a flavor of the progress of vaccine development in several areas of serious and life-threatening non-communicable diseases, I am quoting below the following interesting study:

June 1, 2016 issue of ‘The Independent’ reported that scientists of Johannes Gutenberg University in Germany have taken a “very positive step” towards creating a universal vaccine against cancer that makes the body’s immune system attack tumors as if they were a virus. The researchers had taken pieces of cancer’s genetic RNA code, put them into tiny nanoparticles of fat and then injected the mixture into the bloodstreams of three patients in the advanced stages of the disease. The patients’ immune systems responded by producing “killer” T-cells designed to attack cancer.

This vaccine was found to be effective in fighting “aggressively growing” tumors in mice. At the same time, such vaccines are fast and inexpensive to produce, and virtually any tumor antigen (a protein attacked by the immune system) can be encoded by RNA, the report said.

How expensive are the R&D costs for vaccines?

In this context, an important related question may well be raised: How expensive are the R&D costs for vaccines? According to a paper published by the US National Library of Medicine and National Institute of Health (NIH):

“A vaccine candidate entering pre-clinical development in 2011 would be expected to achieve licensure in 2022; all costs are reported in 2022 Canadian dollars (CAD). After applying a 9 percent cost of capital, the capitalized total R&D expenditure amounts to $ 474.88 million CAD.”

Some key issues and challenges:

Scientific breakthroughs in genetics and biotechnological research, supported by state of art tools related to information technology, a wide range of vaccine development initiatives, targeting both in infectious and non-infectious diseases, are making rapid progress. However, as I had said before, there are some key issues and challenges that need to be addressed, simultaneously. A few examples of which are as follows:

Actual cost of vaccines goes much beyond their R&D expenses. This is mainly because of dedicated and highly specialized manufacturing facilities required for their mass-scale production, and then for the distribution of the same, mostly using cold-chains.

Around 60 percent of the production costs of vaccines are fixed in nature (National Health Policy Forum. 25. January 2006:14). Thus, such products will need to have a decent market size to be profitable.

Unlike many other medications for chronic ailments, which need to be taken for a long duration, vaccines are administered for a limited number of times, restricting their business potential.

Full neutralization of this cost before keeping a modest margin, could make such high-end vaccines relatively expensive for patients, without adequate financial incentives from the Government.

In conclusion:

The discovery of the interesting vaccine to prevent both fatal and non-fatal heart attacks followed an interesting path, and took a long time of around one and a half decade to go for the phase I human trial. Putting together the facts from the available scientific literatures, the long and arduous path of this journey may be, I reckon, summed up, as follows:

An article published by the Harvard Stem Cell Institute (HSCI) on June 9, 2014 first reported that it’s plausible to prevent heart attacks with vaccination. Nonetheless, it all started even much before that, when in 2003, a group of researchers in France studying families with very high cholesterol levels and very early heart attacks, discovered a specific cholesterol regulator. Mutations in the related gene seemed to be responsible for very high cholesterol levels, and early heart attacks. Further research on the subject continued thereafter, based on this novel finding.

Thereafter, in 2014, HSCI scientists collaborating with researchers at the University of Pennsylvania developed a “genome editing” approach for permanently reducing cholesterol levels in mice with a single injection, potentially reducing heart attack risk by up to 90 percent, reported this Harvard article. ‘Circulation Research’ – a journal of the American Heart Association, published the study online on June 10, 2014.

Currently, in mid 2017, from the article published in the peer-reviewed ‘European Heart Journal’ we get to know that development of a vaccine that can prevent heart attacks is going for phase I clinical trial, following several well-tested and scientific evidence based promises.

The outcome of the final phases of this study will now be keenly followed by the experts. Others will optimistically wait for the D-day – virtually the dawn of a new paradigm of preventing heart attacks through vaccination, well before it can result into any fatal or crippling consequences.

By: Tapan J. Ray

Making ‘National Policy For Rare Diseases’ More Meaningful With ‘Orphan Drugs Act’

Posted on July 3, 2017 by Tapan Ray

In November 2016, while hearing a related case, the Delhi High Court reportedly directed the Union Government to finalize and implement a policy on rare diseases, with a provision for free treatment with the expensive medications, as will be required by patients.

Earlier in 2014, while passing the judgement in response to a petition filed by a seven-year-old son of a rickshaw puller seeking affordable treatment for the rare disease that he is suffering from, the Delhi High Court concluded that, “every person has a fundamental right to quality health care that is affordable, accessible and compassionate.”

Currently, the treatment for rare diseases costs the patients an arm and a leg, ranging between Rs. 40 lakhs (US$ 62,000 approx.) to Rs 1.70 crores (US$ 267,000 approx.), which is way beyond the reach of most Indians.

Subsequently, on May 26, 2017, the Ministry of Health and Family Welfare filed an affidavit before the honorable Court, submitting a copy of the National Policy for Rare Diseases 2017, stating that it will aim to facilitate effective diagnosis and affordable treatment. This development is indeed good news, especially considering around 6 to 8 percent of the world population suffer from ‘rare diseases’, and India is no exception.

The key highlights of the new policy:

As per available information, following are the 10 major highlights of the National Policy for Rare Diseases 2017:

The Union Government to create a corpus with an initial funding of Rs 100 crores (US$ 16 million). The State Governments would also provide for a similar fund with a 60 percent contribution from the Centre. This corpus is primarily for the treatment of genetic disorders, excluding rare blood diseases, such as, thalassemia and sickle-cell anemia.

For the sustainability of the corpus, Public Sector Units and Corporates will be encouraged for the contribution in these earmarked funds, as part of their corporate social responsibility.

Appropriate institutions will be accredited by the government for diagnosis and treatment of rare diseases.

To ensure adequate availability and reasonable affordability of the drugs for rare diseases, the Drug Controller General of India (DCGI) will consider amending the Drug and Cosmetics Act with requisite provisions to make clinical trials and import of ERTs possible.

The Department of Financial Services to ensure coverage of rare diseases under insurance schemes.

Employees State Insurance Corporation (ESIC) will explore whether the ceiling limit of funding the treatments for rare diseases can be increased through suitable amendments.

The policy recognizes that rare diseases are, in most cases, serious, chronic, debilitating and life-threatening, often requiring long – specialized treatments, and may also lead to some form of handicap, at times extremely severe in nature.

About 50 percent of new cases of rare diseases are in children and responsible for 35 percent of deaths before the age of one, 10 percent between the ages of one, and five years and 12 percent between five and 15 years.

As a preventive measure, the policy may consider the feasibility of providing pre-conception and ante-natal genetic counselling and screening programs for diagnosing genetic disorders, which would provide a choice to parents about giving birth to children with genetic disorders, especially for families that have a diagnosed genetic disorder, or a high risk profile for it.

The policy gives Indian Council for Medical Research (ICMR) the responsibility of creating a patient registry, as India has no epidemiological data on rare diseases.

Rare diseases – definition:

There is no universal definition of rare diseases. For example, while the US defines a rare disease as one that affects less than 200,000 people nationwide, in China, this number changes to 1 in 500,000 people (or neonatal morbidity of less than 1 in 10,000). India doesn’t yet have a clear definition for the same – not even in its new policy for rare diseases.

However, according to Rare Diseases India (RDI) – a foundation for research on rare diseases and disorders, any disease having fewer than 100 patients per 100,000 population fall into this category. Whereas, those ones affecting 2 patients per 100,000 population are described as ultra-rare diseases.

Rare Diseases in India:

The Organization for Rare Diseases in India (ORD), states that 1 in 20 Indians is affected by such diseases. About 6000 to 8000 rare diseases, mostly genetic in nature, have been identified in India. It was initially estimated that over 31 million Indians are suffering from such disorders in the country, many of which still do not have any cure. Moreover, epidemiological data for most of these ailments is hardly available.

To increase awareness for rare diseases, Rare Diseases Day was observed for the first time in India (New Delhi) on February 28, 2010.

Orphan diseases and orphan drugs:

According to RDI, rare diseases are often referred to as ‘orphan’ diseases. Consequently, the drugs that are specifically developed to treat ‘orphan’ or ‘rare disease conditions’ are called ‘orphan drugs’. The reason being, pharma companies do not generally take such drugs through further stages of development for market launch, or in other words, these are orphaned for economic considerations, though are important to save many precious lives.

Need to encourage orphan drug development in India:

According to SanOrphan SA, Geneva, Switzerland, around 65 percent of rare diseases is serious and disabling. Interestingly, about 250 new rare diseases are discovered each year, corresponding to five new rare diseases per week. As the scenario is no different in India, it prompts the need to encourage development of effective and affordable orphan drugs in the country.

However, without appropriate ecosystem being in place, developing an orphan drug in India, specifically to treat a very small number of such patient populations, through a cost intensive R&D initiative with a low potential of return on investments, is indeed a challenging proposition for many pharma players. Although, in the western world, this trend has started changing now, driven by various other commercial reasons.

Why should ‘Orphan Drugs Act’ follow the National Policy on rare diseases?

National Policy for Rare Diseases is undoubtedly a good beginning, though was brought under the directive of Delhi High Court. Nevertheless, to encourage ‘Orphan Drugs’ development within the country, a robust ‘Orphan Drugs Act’ should now logically follow.

One may well ask, why is this Act is so necessary in India? This is because, the new ‘National Policy for Rare Diseases’ charts just the pathway of a course of action that the Government is planning to take in this area. Policies, as we know, though, are a set of well-articulated intents, do not guarantee that these will be successfully followed to achieve the pre-set long-term goals. Whereas, all legislative Acts or duly enacted laws, are legally enforceable. It is worth noting, while the national policies can be formulated by the government, an Act must be passed by the lawmakers in the Parliament.

Consequently, it is now a well-accepted fact that ‘Orphan Drugs Act’ encourages development of drugs for rare diseases. In an article titled, “What the Orphan Drug Act has done lately for children with rare diseases: a 10-year analysis”, published by the National Center for Biotechnology Information (NCBI), U.S, National Library of Medicine, the authors highlighted that in the U.S. 1138 orphan drugs were designated and 148 received marketing approval, of which 38 (26 percent) were for pediatric diseases, from 2000 to 2009. The percentage of approvals for pediatric products increased from 17.5 (10 of 57) in the first half of the decade, as compared to 30.8 (28 of 91) in the second half. Based on these data, the paper concluded that the incentives provided in the ‘Orphan Drugs Act (ODA)’ of the United States of America, have led to increased availability of specific drugs for the treatment of ‘Rare Diseases’ in the country.

Other countries did – why not India?

1983 signaled the importance of ‘Orphan Drugs’ with the ‘Orphan Drugs Act (ODA) in the U.S.A. A decade after, in 1993, Japan took similar initiative followed by Australia in 1999. Currently, Singapore, South Korea, Canada and New Zealand are also having their country specific ODAs.

Following similar footsteps, India should also encourage its domestic pharmaceutical industry to get engaged in research to discover drugs for rare diseases by putting an ‘Orphan Drugs Act’ in place, extending financial support, tax exemptions and regulatory concessions like smaller and shorter clinical trials, among several other areas, without delay.

Opportunities galore:

The above constraints in the development of orphan drugs have now been turned into an opportunity galore by the global pharma industry, where the domestic players should not lag much behind. Orphan drugs, backed by adequate financial incentives provided by laws in different countries, are now seen as a research and development priority to significantly boost the top and the bottom-line of pharma business.

As IgeaHub has highlighted, orphan drugs, though, cater to a small patient pool, the remunerative price of these drugs offsets the commercial challenges, as mentioned earlier. For example, in 2010, Soliris, which treats paroxysmal nocturnal hemoglobinuria (PNH) that affects 1 out of 500,000, was considered as the industry’s most expensive drug amounting to US$ 409,000 per year of treatment, which generated a total of US$ 541 million revenue for Alexion Pharmaceuticals in that year. In 2012, Soliris recorded a sales turnover of US$ 1.13 billion, which is expected to cross the mark of US$ 3.40 billion in 2018. Further, in 2012, the top selling orphan drug in the USA – Rituxan of Roche – used for the treatment of chronic lymphocytic leukemia, generated US$ 7.15 billion in total sales. Post patent expiry, in 2018, the same drug is expected to yield a revenue of US$ 6.99 billion.

The market:

Evaluate Pharma’s Orphan Drug Report 2017 estimates the worldwide Orphan Drug Sales of total US$ 209 billion, with CAGR of +11 percent for 2017 to 2022 period, which is double of the overall prescription Market Growth. Excluding generics orphan drugs are set to contribute 21.4 percent of Worldwide Prescription Sales by 2022.

Big pharma dominates this segment. Seven of the top 10 companies’ orphan drug sales are from global industry players, who have won approval for their biggest products in various niche indications.

Other commercial benefits:

Thomson Reuters reported additional commercial opportunities with an appropriate ODA, which in the United States are as follows:

15 percent of the ‘Orphan Drugs’ analyzed by them had subsequent launches for other rare illnesses.

6 out of the top 10 ‘Orphan Drugs’ had more than one rare disease indication, with an average peak sales of US$ 34.3 billion in overall sales potential, against around US$ 8.1 billion of the same for drugs with single indication.

Time taken for Clinical Trials (CT) focused on orphan drugs is significantly shorter with much quicker review time than trials involving non-orphan drugs.

Conclusion:

Some of the ‘orphan diseases’ are now being diagnosed also in India, and with precision. As the nation takes rapid strides in the medical science, more of such rare diseases are likely to be diagnosed in our country. The global pharma industry has already started taking rapid strides in this area, supported by ODA in various countries. Similar opportunities, both for the patients, as well as, for the industry, need to be made available in India too.

One of the ways to encourage the orphan drug development in India is to follow the model of the Council of Scientific and Industrial Research (CSIR) for ‘Open Source Drug Discovery’ (OSDD)’ with both global and local partnerships and collaboration.

However, speedy enactment of an appropriate ODA for the country, providing adequate financial incentives to the pharma players, for developing and marketing such drugs, both in the local and global markets, at a reasonably affordable price, would go a long way, and be a win-win situation for all.

Alongside, leveraging the knowledge of OSDD acquired by the CSIR, and framing a robust win-win Public Private Partnership (PPP) model to discover and commercialize the orphan drugs, India could well demonstrate the zeal of the country to move beyond the National Policy for Rare Diseases. In that process, it would be able to offer more meaningful and sustainable benefits, both to the domestic pharma industry and the patients, alike, for a long time to come.

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.

Do Consumers Perceive Pharma Industry Innovative?

Posted on June 26, 2017 by Tapan Ray

One of the world’s richest and most powerful American pharma associations, having an equally strong indirect global presence, apparently, expects all concerned to give an emphatic affirmative answer to the above question.

Vindication of this thought gets reflected in the self-description of the association claiming, it “represents the country’s leading innovative biopharmaceutical research companies. Our members are devoted to discovering and developing medicines that enable patients to live longer, healthier and more productive lives. New medicines are an integral part of the health care system, providing doctors and patients with safe and effective treatment options, and improving quality of life.”

Nearer home, the reverberations of the same could be felt when Novartis lost the Glivec patent case in the Supreme Court of India. At that time, the Wall Street Journal quoted Eric Althoff – a spokesman of Novartis saying, “If innovation is rewarded, there is a clear business case to move forward. If it isn’t rewarded and protected, there isn’t.”

In sync with this self-belief, all pharma trade associations, located across the world, intensely lobbying for the ‘research-based’ global drug companies, together with their individual members, also expect the stakeholders to believe, as if, innovation is the middle name of the pharma industry. This process continues unabated, though, is expensive, and costing millions of dollars every year.

This core intent of doing so, may well be a statement of fact to some, and a contentious one to many, for various reasons. Be that as it may, as the proof of the pudding lies in eating, it is worth ferreting out how successful these efforts have been with the consumers of pharma products. Do they generally buy this concept, and if not, why?

In this article, I shall try to explore the overall scenario in this area.

A recent study:

A recent study results released on June 12, 2017, based on a survey on this issue, and that too conducted in the homeland of pharma innovation – America, brings to the fore a startling fact. In the absence of any other, better and more credible recent study, I shall draw upon some relevant facts from this report.

Klick Health Health – reportedly one of the world’s largest independent health marketing and commercialization agency headquartered in Toronto, Ontario, conducted this survey. As the agency reports, this is an online omnibus survey, conducted between May 19 and May 21, 2017 among 1,012 randomly selected American adults. The margin of error is +/- 3.1 percent. To ensure that the findings are representative of the entire adult population of America, the results have been statistically weighted according to education, age, gender, region, and ethnicity. Discrepancies in or between totals are due to rounding, the report says.

Consumer perception on pharma innovation:

Some of the major findings on consumers’ perception regarding the innovativeness of the pharma industry, are as follows:

Consumers do not believe that healthcare-related industries are particularly innovative today.

Only 17 percent of consumers polled perceive pharmaceuticals & biotech, health & wellness, and hospital sectors as the most innovative, ranking in the 4^th place after consumer electronics (72 percent), telecommunications (87 percent), and media & entertainment (90 percent).

Among health-related industries, respondents ranked health & wellness first in terms of the industry that should be the most innovative (17 percent), quickly followed by pharmaceuticals & biotech (14 percent), and hospitals (9 percent) trailing behind the top 5.

Some other interesting findings:

On innovation and technology, general consumer perceptions are as follows:

91 percent of consumers believe that innovation will positively impact health care over the next five years.

90 percent of respondents say that technology will have a positive impact on their health in the future.

70 percent believe that technology will have the biggest impact in helping them personally manage their own health.nology

Top five technologies predicted to have the biggest impact on people’s health in next five years:

- Health and fitness wearables (21 percent)

- Robotics (15 percent)

- 3D printing (10 percent)

- Smart home devices (9 percent)

- Artificial intelligence (9 percent)

The survey reflects a shift in the consumer mindset from being passive recipients of healthcare to more active and autonomous individuals who appear eager to try more creative and innovative approaches to managing their health.

Another study reflects a similar perception:

Similar negative perception gets reflected in the January 17, 2017 Harris Poll, which reported only nine percent of American consumers believe that pharma and biotechnology drug makers put patients over profits.

January 17, 2017 Harris Poll, while comparing consumers’ perception among different entities in the health care space, found that only insurers have an overall worse reputation than the pharmaceutical industry.

An important area worth exploring:

When consumers do not perceive the pharma industry as innovative as the sector wishes to be, what could possibly be its reasons? While that could be a part of another discussion, it is worth exploring another important area in this article – Do the majority of global pharma CEOs have desired background to lead innovation?

Do the majority of global pharma CEOs have desired background to lead innovation?

This is yet another interesting question. A research article titled “Many CEOs Aren’t Breakthrough Innovators (and That’s OK)”, published in the Harvard Business Review on September 04, 2015 discussed this issue, well-supported by some interesting research data, while coming to a logical conclusion.

The authors indicated that they looked at the background and performance data of 297 CEOs leading the largest companies in three different industries which are widely regarded as innovative: pharmaceuticals, high-tech, and fashion retail. The data captured a 20-year period, from 1995 to 2014 (and includes both current and former CEOs).

The study highlighted, though innovation is widely regarded as important to long-term business performance, CEOs of big pharmaceutical companies, are more likely to have a background as company lawyers, salespeople, or finance managers than in medicine or pharma R&D.

A direct comparison of the same, with the other two industries in the study, which are also widely regarded as innovative, vindicates the above point, as illustrated in the following table:

CEO Background	Pharma (%) (85 CEOs)	High-tech (%) (137 CEOs)	Fashion Retail (%) (75 CEOs)
Specialist background to lead innovation	26	61	60
Industry experience in other management function, e.g. Sales, Production	48	33	29
Background in support functions, e.g. Finance, Legal	26	6	11

In this study, the researchers found that, for pharmaceutical industry CEOs, there is a statistically significant relationship between a CEO’s specialist background and the firm’s performance. A specialist background to lead innovation is worth a 4 percent better shareholder return every year for 20 years, compared to other pharma CEOs in their sample.

Innovations are mostly ‘me-too’, so is the consumer perception:

As the above article reiterates, shorter patent lives of prescription drugs mean companies must continually look for not just any new drugs to fill their pipelines, but more often with breakthrough ones, which are significantly better than what’s already on the market.

Further, the article titled “How to Revive Breakthrough Innovation in the Pharmaceutical Industry”, which is linked to publications on ResearchGate, also indicates, over more than two decades, therapeutics discoveries of pharmaceutical companies more often than not yielded compounds that are only marginally better than existing therapies, rather than breakthrough molecules.

This could well be another contributing factor in the general ‘not so positive’ consumer perception about the global pharma industry, today.

Conclusion:

There may not be a hell of a lot of argument on the fact that the drug industry has a consumer perception problem today. Even the August 2016 Gallup Poll rated pharma as one of the worst industries in the current times.

Is the collective internal effort of continuously trying to associate innovation with the global pharma industry, the right answer for the same? May be, may well be not, though, the global drug industry is incessantly trying to project, as if ‘innovation’ is its middle name, as it were.

Is it working? The obvious answer is available from various recent research studies, as enumerated above. Still, in January 2017, reportedly to rescue the image of its member companies, the Pharmaceutical Research and Manufacturers of America, unveiled a campaign, again basically focusing on innovation, called “Go Boldly.” It reportedly tries to communicate that the pharma industry develops life-saving medicines, and that they help keep medical costs down, because new medicines often reduce hospital stays and chronic illnesses. Is the campaign cost intensive? – Of course, yes. Is it productive? – possibly not. But who cares?

Be that as it may, today’s health care consumers perceive the global pharma industry neither as innovative nor caring, despite all its efforts. Thus, there is an important need for the pharma players to effectively bridge this perception gap in different and more innovative ways.

However, all that one can witness today, is the global pharma industry charting the same beaten path, yet again – with no further innovation in its communication – neither in content nor in its delivery platforms. That said, only time will be able to tell, whether similar efforts, renewed again and again, can reverse the consumer perception on pharma – making it seen as highly innovative and a caring industry for all.

By: Tapan J. Ray

Managing Pharma Investors’ Expectations When The Chips Are Down

Posted on June 19, 2017 by Tapan Ray

Triggered by several critical factors, over a relatively short period of time, a downward spiral is visible with most Indian Pharma stocks, with a significant erosion in market capitalization of many large players in the country.

A set of important factors has been fueling this current downturn since around the last four years. These include, issues related to serious regulatory non-compliance with US-FDA and other foreign drug regulators, pricing pressure both in the domestic and the overseas markets, including the United States, delayed approval of several new generic drugs in the number-one pharma market of the world, for various reasons. Initial rollout period of GST expected to commence on July 1, 2017, may also prompt some major readjustments in the distribution setting of many pharma organizations. This has been further compounded with the wholesalers’ and retailers’ demand for compensation for any losses on input credit arising out of this critical reform.

As eroding market cap generally leads to commensurately lower market valuation of a company, it adversely impacts company’s many business growth related activities, which encompasses attracting low cost – high value investments, and M&A related activities, besides many others. Consequently, this negative swing has alarmed many investors, making them more demanding on company performance – uninterrupted, almost at any cost, as it were.

Not much headroom for necessary course correction:

Unrelenting expectations of this nature from the investors, inclusive of activist shareholders, to continue driving the business growth engine up the steep slope of ever increasing return on investment, is not expected to die down, anytime soon.

They may not be willing to leave enough headroom for the respective pharma management teams to realign their growth path with the changing and challenging needs of time, if it adversely impacts business even in the short-term. Nonetheless, if it is not allowed, the tailspin is likely to continue, as has been happening since, at least, the last couple of years, pushing the business at a dangerous level of sustainability.

Such demand of the investors and shareholders, irrespective of the gravity of the situation where their respective companies are in, may not be too uncommon, even in the global arena. However, many experts are now raising a key question in this area. In this article, I shall try to look at this issue, not just from the investors’ perspective, but also from what the concerned pharma players can and should do in this area, sooner the better.

A pertinent question needs to be addressed:

This important and relevant question is: what is the accountability of the investors, if their pressure for performance when the company is at a crossroad of this nature, causes a long-term irreparable damage to the business?

The very issue has been discussed immaculately in an article titled, “The Error at The Heart of Corporate Leadership”, published in the May-June 2017 issue of the Harvard Business Review.

The paper reiterates that attributing ownership of the corporation to its investors involves a challenging problem of accountability. This is because, ‘shareholders or private investors have no legal duty to protect or serve the companies whose shares they own and are shielded by the doctrine of limited liability from legal responsibility for those companies’ debts and misdeeds.’ Moreover, they are both physically and psychologically distant from the activities of the companies they invest in, and may generally buy and sell these shares without restrictions.

Nevertheless, such strong and ever increasing demands put the top pharma managers under increasing pressure to deliver faster and more predictable returns, regardless of the headwind that the business is facing. The issue becomes more complex when temporary-holders of large blocks of shares intervene to reconstitute a company’s board, change its management, or restructure its finances to drive up the share price, only to sell out and move on to another target, without ever having to answer for their intervention’s impact on the company or other parties, the article highlights.

Export business – the pain points:

“Pharma stocks take a beating on renewed US FDA scrutiny” – flashed the headline of a recent media report of June 12, 2017. As I see it, in the export business, especially in the top pharma market in the world, there appears to be a strong possibility of further worsening the business environment, especially for the Indian drug exporters.

Wave after wave of US-FDA import bans involving many India made drug formulations and Active Pharmaceutical Ingredients (API), since over last four years, have significantly affected the short-term export sales of the domestic pharma exporters. Alongside, these have seriously dented the image of the Indian pharma players, collectively, which encompasses the critical area of regulatory compliance – to offer well-documented safe and effective drugs, as required by the regulator, for the patients in the United States.

The situation gets messier with media headlines, such as, one from Bloomberg’s on January 24, 2017, conveying to the world community – “Document Shredding at Night Raises FDA Eyebrows During India Visit.”

Besides current drug pricing pressure, President Donald Trump’s election pledge for local manufacturing of products consumed in the United States, for more job creation in the country, sends another possible storm signal in this area. This is serious too, as Indian generic drug producers cater to around 40 percent of the total generic drug consumption in America.

Overcoming the odds in export business:

While taking corrective and effective measures for a sustainable long-term business performance, doing the same things more intensely that precipitated the current crisis, would be counterproductive.

Improving the situation, would also call for a strong preparedness for launching new generic products at a regular interval. However, in tandem, there is a crying need for the concerned pharma companies to take a pause, and conclude, a well-structured and expert-guided corporate introspection and brainstorming process, on priority. This will help them to arrive at a set of actionable strategic plans to effectively address each of the pain points, in a meticulous and time-bound manner.

Investors must necessarily be taken on board by opening appropriate communication channels, accordingly. This is to enable them to understand and accept the reasons for a short-term pain for a sustainable long-term gain. The tangible results of corrective measures should subsequently unfold to all concerned, with minor course corrections on-the-run, wherever necessary.

Domestic business – the pain points:

This is again another complex issue, which is often manifested through pressure on drug prices. The blame for such a situation, though originates from somewhere else, generally falls on the Government and the drug price regulator, for obvious reasons. It has a palpable boomerang effect, that is brought out by various research studies, and captured in consumers and the expert opinion, such as one that was published by the Washington Post on June 14, 2017 with the title, “The pharmaceutical industry puts profits above people.”

In the United States, where the drug pricing pressure is widely believed to have primarily originated from the escalating cost containment pressure of the Government and the key health care providers – triggered by a dangerous drug-pricing trend. Whereas in India, in addition to the latter that is related to non-schedule branded generic drugs, it is mostly related high out of pocket expenses on drugs, attempts to dodge various drug price regulations, and ignoring several ethical marketing practices related issues. The net outcome of all this is growing trust deficit on the pharma industry, in general.

Let me illustrate this point with a very contemporary example. On May 18, 2017, Reuters reported, “India’s drug pricing regulator has demanded explanations from 65 domestic and global drug makers for selling new forms of essential diabetes and antibiotic drugs without its approval.” Interestingly, these companies reportedly include many big names, such as, Abbott Laboratories, Sanofi, Novartis and Indian firms such as Sun Pharmaceutical Industries and Lupin.

According to a circular of the National Pharmaceutical Pricing Authority (NPPA) of May 17, 2017, the above companies have allegedly launched formulations by altering an essential drug formulation with strength/dosage other than as specified in the Drug Price Control Order (DPCO) 2013 or combination with another drug not under price control, without even applying for price approval from NPPA as required. NPPA also doesn’t seem to be sure, whether such Fixed Dose Combinations (FDC) are rational or irrational and have the approval of the Central Drug Standard Control Organization (CDSCO).

If so, it’s indeed a sad development and a sorry state of affair, especially for those companies, which do some chest-thumping on ethics and compliance, often browbeating many Indian players, especially on USFDA related issues, besides pharma marketing practices.

As on date, Union Ministry of Health has banned several hundreds of such FDCs – on the ground of being irrational, launched without proper regulatory approval, lacking in therapeutic efficacy and safety profile, which may even cause harm to patients. March 11, 2016 notification of CDSCO banned 296 irrational FDCs.

However, many pharma players have succeeded in obtaining stay orders against almost all such regulatory bans from various High Courts. Nevertheless, the good news is, from July 2017, the Supreme Court is expected to hear all these cases, collectively. There could be another possible downturn in the market, if the Government wins the case.

Overcoming the odds in domestic business:

In these specific areas, there doesn’t seem to be any other option left to satisfy the long-term interest of the investors, other than addressing the ethics, values and compliance issues of the company on the ground, head on. It doesn’t really matter, what is displayed on the subject in their respective websites. Thus, in this area too, there is a crying need for a well-structured and expert-guided corporate introspection and brainstorming process to disrupt the status quo from its very root.

The above process would help the pharma players to arrive at a set of actionable strategic plans to effectively address the ethics and compliance issues in all the pain points – regulatory, marketing or financial, in a meticulous and time-bound manner. Alongside, all the stakeholders, including the investors, to be taken on board through customized content and the engagement platforms, to put the companies back into the long-term growth trajectory.

In conclusion:

Investors are very important, but if they aren’t an integral part of the corporate management team, should not try to overwhelm the business management process, especially for any short term financial gain. Attributing such authority to investors, involves a challenging problem of accountability for action, as they can get in or out of their investments at any time they choose to do so.

However, it’s also one of the key responsibilities of the management to listen to them, seriously. Take them on board by appropriately explaining to them in every critical situation, the broad strategic direction that the company would follow in pursuit of excellence. Thereafter, demonstrable outcome of all management action against the top operational goals, should be placed before them at a periodic interval, on an ongoing basis.

This process, if carried out with absolute transparency, integrity and seriousness, could help the Indian pharma players getting enough breathing space from the investors, for making the right operational interventions, before it’s too late.

Earlier this year, stepping down of former CEO of GSK – Andrew Witty, was reported to be due to pressure from investors for below par sales and profit in the past three years, besides a few other reasons. Another recent report of June 15, 2017 on “rebel investors looking to remake the board of Mylan” would possibly reinforce this point, further.

Outside the pharma industry, such a situation is not uncommon now, even in India. Besides, what happened recently in Tata Sons, the June 14, 2017 media headline highlighting “Infosys flags ‘activist shareholder’ as risk factor”, vindicates the same point, yet again.

Thus, managing pharma investors’ expectations through a process of continuous engagement with them, effectively, especially when the chips are down, as it is today, is so critical for the long-term success and sustainability of pharma business. Maintaining the status quo any further, would possibly make a high-flying pharma player to experience the strong gravitational pull, uncontrolled, with its its serious but avoidable consequences.

By: Tapan J. Ray

The Relevance of Content Marketing In Pharma

Posted on June 12, 2017 by Tapan Ray

“Nearly half of pharma industry may come under price control” – was the headline of a media report of June 7, 2017. Although, National Pharmaceutical Pricing Authority (NPPA) has apparently denied any such move, the fact is that the number of drugs coming under price control is steadily creeping up, ever since the Drugs Price Control Order 2013 came into force. If this trend continues, the gross profit margin of most of the branded generic manufacturers will also keep getting significantly squeezed, with a varying degree, though.

Coupled with drug pricing pressure in the United States, USFDA import bans from several manufacturing plants in India and dwindling number of new generic drugs ready for US launch, the market capitalization of many publicly listed pharma companies, may go further south. An important example of this situation was cited by Bloomberg, with reasons, in its report of June 07, 2017 carrying a headline “Pharma Woes Axe $14 Billion From Wealth of Once-Richest Indian.”

However, the overall setting is not so distressing for all Indian drug manufacturers, for different reasons. The June 08, 2017 headline of another business news daily stating – “Cadila Healthcare overtakes Lupin as second most valuable pharma company in India,” vindicates the point. The promoter of this company reportedly said, ‘the company expects to receive 40 product approvals in the US in the current financial year.’

Be that as it may, added to these pain points of many pharma players in the country, Prime Minster Narendra Modi’s recent hint on framing rules for doctors to prescribe generic drugs, invites yet another wave of worries for the branded generic drugs players in India, regardless of a solid socioeconomic reason for the same.

Keeping these developments in perspective, collectively, the headwind faced by the Indian pharma industry, regardless of the underlying reasons, is indeed a tough one to navigate through, unscathed. Consequently, the stellar aggregate net profit growth of 41.3 percent in 2016 over 2015, as reported by the 2016 Dun & Bradstreet publication titled, “India’s Leading Pharmaceutical Companies 2016”, could possibly be rather challenging to maintain. Let me hasten to add that a much slower rise in the sector’s largest expense head – ‘raw material expenses’, also helped to achieve this enviable profit growth in 2016, as the report elaborated.

In this article, I shall try to fathom the depth this issue, and the possible way forward.

Areas of laudable contribution by the pharma industry:

For several decades, the pharmaceutical industry has been playing a leading role, not just in offering new innovative drugs, but their cheaper generic equivalents also, as those go off-patent, incessantly, to save and improve the quality millions of lives, across the world. The success of the drug industry is fundamentally driven by innovation – both in the discovery of new molecules and treatments, as well as in coming out with new cost efficient processes to significantly improve patients’ access to innovative drugs, post patent expiry.

Two areas requiring greater focus:

In tandem with these laudable initiatives, two disturbing trends are gathering momentum. One such trend is inadequate understanding of the grave fall out of not meeting with important stakeholders’ expectation on product pricing. As a result, various Governments and other health care payers are coming down heavily on pharma players to make drug prices affordable for the patients.

And the second one is, an intriguing apathy to be innovative in engaging with each stakeholder to take them on board. This can be done by communicating transparently, an easy-to-understand way and a customized way, the major benefits the individual players have been providing to facilitate various public health care initiatives. An apparent disinterest in this area continues, despite the snowballing effect of adverse public perception, and increasing trust deficit.

The core factors driving the trends:

These two trends are generally driven by two core factors – one is external, and the other internal. The external one is related to the general socioeconomic environment, and the internal one is intimately related to strategic business game plans of individual pharma companies.

The discussion will get more complex, if one wants to know whether the traditional pharma business models have a catalytic effect on the seemingly hostile business environment. As I have discussed several times in this blog, what the pharma players can possibly do in the pricing area, I shall not go into that subject yet again.

Nevertheless, what the pharma companies can do in the second area, to achieve their key strategic business goals, is quite different from what most of them are doing or not doing, till date. As we see around, many pharma players, especially the Indian branded generic companies remain engaged predominantly with the doctors, in the form of product detailing, or through Continuing Medical Education (CME) events, or the likes of these.

Today’s newer kind of strategic intervention calls for expert inputs. This is essential to create credible-research-based innovative content, and deliver the same with absolute precision through tailor-made platforms, for effective engagement with each stakeholder. It goes without saying, this should be done in a way that ordinary citizens or netizens can easily relate to.

Relevance of ‘Content Marketing’:

As the traditional pharma marketing is becoming progressively less and less effective, the need for a comprehensive content marketing model is becoming critical for the Indian pharma industry, more than ever before. In this model, useful content will be at the core of pharma marketing

According to the Content Marketing Institute (CMI): ‘Content Marketing is a strategic marketing approach focused on creating and distributing valuable, relevant, and consistent content to attract and retain a clearly defined audience – and, ultimately, to drive profitable customer action.’

It is possible to make the demand of a medical product, or a caring corporate image, more sustainable through content marketing, as compared to the traditional ones where individual product detailing and CMEs become the centerpieces of marketing strategy.

Why is it so important for pharma now?

According to a Pew Research Study, “One in three American adults have gone online to figure out a medical condition.”

Similarly, PwC Health Research Institute’s consumer survey of 1,060 US adults highlights, about one-third of consumers are using the social space as a natural habitat for discussions on health. More than 80 percent of individuals aged between18 and 24 would likely to share health-related information through social media, while nearly 90 percent of individuals would engage in health-related activities, or trust information found via social media. Around 45 percent of consumers said information from social media would affect their decisions to seek a second opinion.

In India too, increasing number of doctors and patient populations are ferreting information that they require from cyberspace, including different expert websites, online, and immediately when they require those.

Doctors are searching for detail information on different drugs, about their manufacturers, new treatment processes, and required data on clinical trials. Similarly, patients are searching for information in various other areas, such as, different aspects of the diseases that they or their near or dear ones are suffering from, and their effective modes of treatment with cost data, by getting connected online with related patient groups or communities. Even when engaging with the doctors, they often want to cross verify the outcome of discussion with the information available on the Internet. So do the doctors with the information provided by the pharma companies in person.

For example, one such popular website, among many others, is The Mayo Clinic’s Sharing blog designed for the Mayo Clinic community, and includes the following area:

Sharing experience of patient communities
Specialist doctors discussing new treatments, contemporary innovation in the health care space and patient care
Medical researchers and specialist doctors sharing their research experiences
Discussion on future health care and wellness by the professionals at Mayo Clinic
Students sharing their experience and perspectives in various areas

Driven by the current digital wave, and the word of mouth publicity to the benefits derived by the doctors and patients through such process, an ever-increasing number of the population is expected to do the same, in the years ahead.

Thus, a huge marketing opportunity in this much unexplored area awaits the Indian pharma players to establish an emotional connect with the stakeholders, including the doctors and patients, by providing all relevant information that they are web-searching for.

Needs specialization:

Unlike traditional pharma marketing, content marketing is a highly-specialized area – especially for the generation of requisite meaningful and quality data, getting the relevant insight through analytics for innovative message creation.

Moreover, as the current public image of pharma players, in general, is not very encouraging, it may be a good idea to work on various trust building activities. These may include videos on patients narrating their stories or a research experience, and infographics. Thereafter, its delivery through best suited communication platforms, across the marketing channels, followed by constant evaluation of the quality impact generated, will be critical.

Content marketing initiative in pharma should ideally start on a pilot scale and curated to enhance stakeholder engagement level, as necessary, before scaling it up to a national or a global level, as the situation would call for.

A few examples:

Some global pharma players have initiated great work in the space of content marketing. These are aimed at mostly to increase the awareness level and educate patients, doctors, and caregivers in some important and carefully crafted areas. A few examples are as follows:

Actually She Can (Allergan): on contraception options
Set Your Sights (Novartis): on vision conditions that a person may not have been previously aware of
Living Like You (Novartis): on coping with Multiple Sclerosis at its different stages
Arthritis.com (Pfizer): provides information about rheumatoid arthritis and osteoarthritis
Quitter’s Circle (Pfizer and American Lung Association): provides resource for those who want to quit smoking and their supporters.

Conclusion:

The most predictable part in the pharma business environment is its unpredictability. What is happening today with various large and seemingly invincible players of the recent past, is indeed jaw dropping. Some experts had predicted that the ultimate outcome of getting fixated into mostly traditional business practices in a rapidly changing socioeconomic setting and technology focused environment, could seriously challenge the long-term sustainability of a business.

The major adverse impact on the Indian pharma sector’s overall business performance is primarily driven primarily by the product pricing pressure and USFDA import bans on product quality parameters. Many believe, both these are intimately related to the current business practices of the industry, in general, leading to increasing trust deficits between the pharma companies and the Government, including the public.

The growth engine of the pharma industry is innovation, which would always remain so. Interestingly, in marketing areas no much innovation is noticed. Continuous and effective engagement with all stakeholders is critical now, not just for brand promotion, but also on corporate mission, vision and values, giving solid examples of how the company is making steady progress in those areas. This would help establish credibility in their eyes and take them on board to create a powerful and trustworthy voice for effective brand engagements, as well. It will also encourage the pharma players to ‘walk the talk’, in the real world, always.

The opportunities that a comprehensive content marketing strategy could offer to pharma companies to move in this direction, are phenomenal. It helps to get emotionally connected with all stakeholders, by providing relevant information, including those they are web-searching for, in a more innovative and informative format.

By: Tapan J. Ray

Is The Global Generic Drug Market Slowing Down?

Posted on June 5, 2017 by Tapan Ray

Driven by a strong environmental headwind, both within and outside the country, several pharma companies in India have recently started raising a red flag on their future earning guidance for the stock market, though citing quite different reasons altogether. Quoting the following two recent examples, I shall illustrate this point:

“For decades, the generic drug business has followed a simple model for growth: wait for a chemical medicine to go off patent, then copy it. But 2018 promises to be one of the industry’s last big bumper crops, with $27.8 billion worth of therapies losing protection. The following year’s haul drops by almost two thirds, and the year after it shrinks even further” – reported the May 27, 2017 article in Bloomberg titled, ‘Pharma Heir Seeks a New Holy Grail as Generic Drugs Run Dry,” quoting the promoter of Glenmark.

Another May 27, 2017 article by Reuters also quoted similar business sentiment, though for a much different reason, of the world’s fifth-largest generic drug maker – Sun Pharma, following similar concerns of Dr. Reddy’s Laboratories Ltd and Lupin Ltd. Here, the promoter of Sun Pharma said, “We may even have a single digit decline in consolidated revenue for full-year 2018 versus full-year 2017.”

These red flags, though signal different reasons, prompt some fundamental questions: Is the global generic drug market, especially the US, slowing down? If so, what then is the real reason of the anticipated business slow-down of large Indian pharma players? Is it due to lesser number of patented products going off-patent in the future years, or is it due to pricing pressure in various countries, including the US, or a combination of several other factors alongside? In this article, I shall deliberate on this emerging concern.

Global generic drug market – the past trend:

Several favorable environmental factors have been fueling the growth of generic drug prescriptions across the world, and the trend continues going north. Currently, the growth of generic drug prescriptions is outpacing the same for the patented ones. According to the April 2017 research study titled “Generic Drugs Market: Global Industry Trends, Manufacturing Process, Share, Size, Growth, Opportunity and Forecast 2017-2022”, published by IMARC, the global generic drug market was valued at around US$ 228.8 Billion in 2016, growing at a CAGR of around 9 percent during 2010-2016.

This trend has been well captured in numbers, from various different angles, in the September 2016 report of Evaluate Pharma, as follows:

Global trend of prescription generic drug sales (2008-2015)

Year	2008	2009	2010	2011	2012	2013	2014	2015
Global Rx Drug Sales (2008-15) (US$ Billion)	650	663	687	729	717	724	749	742
Growth per Year (%)		+2.0	+3.5	+6.1	(1.6)	+0.9	+3.5	(1.0)
Rx Generics Drug Sales (US $Billion)	53	53	59	65	66	69	74	73
Generics as % of Total Rx Drugs	8.2	8.0	8.6	9.0	9.2	9.5	9.9	9.9
% Market at risk to patent expiry or available for new generic drugs entry	3.0	4.0	4.0	5.0	7.0	4.0	5.0	6.0

(Table 1: Adapted from the report ‘World Preview 2016, Outlook to 2022’ of EvaluatePharma, September 2016)

The Table 1 shows, while the overall global sales growth of prescription drugs faltered during 2012-15 period, mainly due to after effects of patent expiry of several blockbuster drugs, the general trend of generic drug sales continued to ascend. As we shall see below, the projected trend in the succeeding years is not much different, either.

Global generic drug market – present, and projected future trend:

The global generic drug market is currently growing at a faster pace than the patented drugs, and this overall trend is likely to remain so in future too, as we shall find below.

Globally, North America, and particularly the US, is the largest market for generic drugs. According to the QuintilesIMS 2016 report, generic drugs saved patients and the US health care system US$227 billion in 2015. Although around 89 percent of the total prescriptions in the US are for generic drugs, these constitute just 27 percent of total spending for medicines. In other words, the share of patented drugs, though, just around 11 percent of total prescriptions, contribute 73 percent of the total prescription drug costs.

Backed by the support of Governments for similar reasons, Europe is, and will continue to register impressive growth in this area. Similarly, in Latin America, Brazil is the largest market for generic drugs, contributing 23 percent and 25 percent of the country’s pharma sector by value and by volume, respectively, in 2015.

Major growth drivers to remain the same:

The following major factors would continue to drive the growth of the global generic drug market:

Patent expiration of innovative drugs
Increasing aging population
Healthcare cost containment pressure, including out of pocket drug expenditure
Government initiatives for the use of low cost generic drugs to treat chronic diseases
Despite high price competition more leading companies are taking interest in generic drugs especially in emerging markets

India – a major global player for generic drugs:

India and China dominated the generic drug market in the Asia pacific region. India is the largest exporter of the generic drug formulations. A large number of drug manufacturing plants belonging to several Indian players have obtained regulatory approval from the overseas regulators, such as, US-FDA, MHRA-UK, TGA-Australia and MCC-South Africa. Consequently, around 50 percent of the total annual turnover of many large domestic Indian drug manufacturers comes from exports. The top global players in the generic drug market include Teva Pharmaceuticals, Novartis AG, Mylan, Abbott, Actavis Pharma and India’s own Sun Pharma.

No significant change in the future market trend is envisaged:

When I compare the same factors that fueled the growth of global prescription generic drug market in the past years (2008-2015) with the following year (2016), and the research-based projections from 2017-2022, no significant change in the market trend is visible.

Global trend of prescription generic drug sales (2015 – 2022)

Year	2015	2016	2017	2018	2019	2020	2021	2022
Global Rx Drug Sales (2015-22) (US$ Billion)	742	778	822	873	931	996	1060	1121
Growth per Year (%)	(-1.0)	+4.8	+5.7	+6.2	+6.6	+7.0	+6.5	+5.7
Rx Generics Drug Sales (US $Billion)	73	80	86	92	97	103	109	115
Generics as % of Total Rx Drugs	9.9	10.3	10.5	10.5	10.4	10.4	10.3	10.3
% Market at risk to patent expiry or available for new generic drugs entry	6.0	6.0	4.0	4.0	4.0	2.0	2.0	5.0

(Table 2: Adapted from the report ‘World Preview 2016, Outlook to 2022’ of EvaluatePharma, September 2016)

The Table 2 shows, the overall global sales growth trend of prescription drugs appears a shade better in 2008-15 period, even with the after effects of patent expiry (Table 1), as compared to 2016-22. The scope for entry of new generic drugs goes below 4 percent of the total prescription drug market only in two years – 2020 and 2021. Thus, any serious concern only on this count for a long-term growth impediment of the global generic drug market, post 2018, doesn’t seem to be based on a solid ground, and is a contentious one. Moreover, the sales trend of prescription generic drugs as a percentage of the total value of all prescription drugs, hovers around 10 percent in this statistical projection, which is again a shade better than around 9 percent of the past comparable years.

What triggered the major pricing pressure?

With its over 40 percent of the total pharmaceutical produce, predominantly generic drug formulations, being exported around the world, India has become one of the fastest growing global manufacturing hubs for medicinal products. According to Pharmaceutical Export Promotion Council of India (Pharmexcil), United States (US) is the largest market for the India’s pharma exports, followed by the United Kingdom (UK), South Africa, Russia, Nigeria, Brazil and Germany.

Since long, the largest pharma market in the world – the US, has been the Eldorado of pharma business across the globe, mostly driven by the unfettered freedom of continuously charging a hefty price premium in the country. Thus far, it has been an incredible dream run, all the way, even for many large, medium and small generic drug exporters from India.

However, ongoing activities of many large drug companies, dominated by allegedly blatant self-serving interests, have now given rise to a strong general demand on the Governments in different countries, including the US, to initiate robust remedial measures, soon. The telltale signs of which indicate that this no holds barred pricing freedom may not be available to pharma, even in the US, any longer.

Self-inflicted injury?

The situation where several major Indian generic companies are in today, appears akin to an avoidable self-inflicted injury, basically falling in the following two important areas. Nonetheless, even after the healing process gets over, the scar mark would remain for some more time, till the business becomes as usual. Hopefully, it will happen sooner than expected, provided truly ‘out of box’ corrective measures are taken, and followed up with a military precision.

Huge price hikes:

According to the Reuters report of September 11, 2016, US Department of Justice sent summons to the US arm of Sun Pharma – Taro Pharmaceutical Industries Inc. and its two senior executives seeking information on generic drug prices. In 2010, Sun Pharma acquired a controlling stake in Taro Pharmaceutical Industries.

On September 14, 2016, quoting a September 8, 2016 research done by the brokerage firm IIFL, ‘The Economic Times’ also reported that several large Indian generic drug manufacturers, such as, Sun Pharma, Dr. Reddy’s, Lupin, Aurobindo and Glenmark have hiked the prices of some of their drugs between 150 percent and 800 percent in the US. These apparently avoidable incidents fuel more apprehensions in the prevailing scenario. As I wrote in this Blog on September 12, 2016, the subject of price increases even for generic drugs reverberated during the last Presidential campaign in the US, as well.

Serious compromise with product quality standards:

Apprehensions on dubious quality standards of many drugs manufactured in India have now assumed a gigantic dimension with import bans of many India made generic drugs by foreign drug regulators, such as US-FDA, EMA and MHRA. Today, even smaller countries are questioning the Indian drug quality to protect their patients’ health interest. This critical issue has started gaining momentum since 2013, after Ranbaxy pleaded guilty and paid a hefty fine of US$ 500 million for falsifying clinical data and distributing allegedly ‘adulterated medicines’ in the United States.

Thereafter, it’s a history. The names of who’s who of Indian drug manufacturers started appearing in the US-FDA and other overseas drug regulators’ import ban list, not just for failing to conform to their quality standards, but also for willful non-compliance with major cGMP requirements, besides widely reported incidents of data fudging and falsification of other drug quality related documents.

Global murmurs on generic drug quality among doctors:

There are reported murmurs both among the US and the Indian doctors on the generic drug quality standards, but for different drug types and categories.

According to the Reuters article published on March 18, 2014, titled “Unease grows among US doctors over Indian drug quality”, many US doctors expressed serious concerns about the quality of generic drugs supplied by Indian manufacturers. This followed the ‘import bans’ by the USFDA and a flurry of huge Indian drug recalls there. Such concerns are so serious, as India supplies about 40 percent of generic and over-the-counter drugs used in the United States, making it the second-biggest generic drug supplier after Canada.

While the doctors in the US raise overall quality concerns on the products manufactured by the large Indian branded generic companies, Indian doctors are quite at ease with the branded generics. They generally raise quality concerns only on generic drugs without any brand names.

Thus, a lurking fear keeps lingering, as many feel that Indian drug manufacturing quality related issues may not necessarily be confined only to exports in the developed world, such as, the United States, European Union or Canada. There is no reason to vouch for either, that such gross violations are not taking place with the medicines consumed by patients in India, or in the poorer nations of Africa and other similar markets.

In conclusion:

Sun Pharma has publicly expressed its concern that pricing pressure in the US may adversely impact its business in 2018. There doesn’t seem to be any major surprise on this statement, as many believe it was likely to happen, though for a different reason, since when the global media reported in September 2015: “FDA revokes approval for Sun Pharma’s seizure drug over compliance issues.”

As investors are raising concerns, the following comment by the Co-Chairman and Chief Executive of Dr. Reddy’s Laboratories, reported by ‘Financial Express’ on August 24, 2015, well captures the vulnerability of Indian generic drug business in this area: “The U.S. market is so big that there is no equivalent alternative. We just have to get stronger in the U.S., resolve our issues, build a pipeline and be more innovative to drive growth.”

Inadequate remedial measures could unleash this pressure to reach a dangerous threshold, impacting sustainable performance of the concerned companies. On the other hand, adequate remedial action, both strategic and operational, could lead to significant cost escalation, with no space available for its neutralization through price increases, gradually squeezing the margin. It will be a tight rope walk for many in the coming years.

As research reports indicate, the global generic drug market is not and will not be slowing down in the long term, not even in India. There may be some temporary ups and downs in the market due to pricing pressure, and the number of novel products going off-patent in some years. Nevertheless, the traditional business models being followed by some large companies may retard their respective business growth, considerably.

The pricing pressure is a real one. However, from the Indian perspective, I reckon, it’s primarily a self-inflicted injury, just as the other major one – the drug import bans on the ground of serious compromise with product quality standards. Many Indian generic drug players don’t believe so, and probably would never will, publicly.

By: Tapan J. Ray

Rebalancing Skill Sets In Pharma Sales And Marketing

Posted on May 29, 2017 by Tapan Ray

A disturbing trend against much needed more job creation across the world, has been well captured in a May 2016 MIT article. It concluded through several complex mathematical models that: “As more tasks performed by labor are being automated, concerns that these new technologies will make labor redundant have intensified.”

However, despite well-hyped concerns in this area, ongoing rapid advancement of technology and other related innovation haven’t yet caused any alarming level of unemployment anywhere in the world, nor it possibly will. Several instances of gradual reduction in the number of routine and traditional jobs due to such automation, are generally related to a lesser level of hard skill sets. As we shall see below, many industries require doing so in the modern times, for long term sustainability of business.

In tandem, promising high tech jobs requiring state or the art hard skill sets are getting created too, though are fewer in number. Nevertheless, the number of brilliant startups has increased by manifolds, during the same period. This change is inevitable, mostly in any science and technology driven industry, e.g., banking sector, where most of human operated bank tellers have made way to ATM machines.

A recent vindication:

Vindicating this point, as it were, on May 18, 2017, Reuters reported that Swiss pharma major Novartis, as a part of its “ongoing global transformation” initiative launched last year to create a unified operating model, will cut around 500 traditional and routine jobs in Switzerland, and add 350 in high-tech areas. Immediately thereafter, for similar reasons, the company announced the elimination of another 250 jobs in the United States.

Jobs are important to all for a living. Any job loss, irrespective of the nature of business compulsion, is indeed unfortunate. That said, whether we like it or not, such evolving trends are the stark realities, and expected to continue or even accelerate in the years ahead for higher growth in productivity, especially involving the routine and traditional tasks.

Pharma industry, though a science-based one, loss of routine and traditional jobs due to technological advancement is fortunately still much less as compared to other similar industries. This is primarily due to the continuation of the traditional business models in the pharma sector, requiring a huge number of human intervention, which call for a different balance of soft and hard skill sets.

However, crystal gazing the future, it appears quite likely that there will be a strong need to rebalancing the required soft and hard skills in the drug industry. The contour of my discussion in this article will be on pharma sales and marketing.

Skill – the ability to do something well:

The Oxford dictionary defines ‘skill’ as ‘the ability to do something well’. Similarly, the term ‘ability’ has been defined by it as ‘possession of the means’. Thus, ‘skill’ means ‘possession of the means to do something well’. It is an absolute must in all professions, including pharma sales and marketing.

Skills broadly fall into two categories – hard and soft skills. Hard skills involve specific knowledge and teachable abilities that can be defined and measured and are usually quantifiable.

Hard skills are individual proficiency in various scientific, technical, mathematical and even some artistic areas of creation, besides other related ones. In pharma sales and marketing arena of the near future, these include, among others, robust scientific knowledge-base to understand various aspects of drug molecules, content creation with astute market understanding, data generation and analysis through state of art analytics and research, software programing, digital savviness and social media expertise. Many of these skills are related to the Intelligent Quotient of an individual.

Soft skills, on the other hand, are less tangible and quantifiable, such as etiquette or personality development; work ethics, getting along with people, ability to listen patiently, overcoming objections, persuading others and a deep sense of accountability. Many of these skills are usually related to emotional intelligence of an individual.

Which one is more important?

Both hard or soft skills are useful, valuable and important. However, the mix of these two skills for high performance of any individual professional will generally depend on success requirements of a job in a specific macro business environment.

That said, it is important to note that most of the hard skills are taught and learnt mostly before a person’s entry into science, technology or various other craft or design based jobs. The related hard skills are essential for getting selected for specialized jobs. Whereas, softer skills are usually learned on the job, and through experience by all those who want to grow in the profession.

In this context, it may not be a bad idea for all pharma sales and marketing professionals to take a hard look at our own current soft and hard skill sets again, against rapidly changing demands of the business environment. Regardless of where we are now, it will be worth writing down on a piece of paper the type of each of these two skills, in order of their strengths, that we individually possess, which are good enough for achieving sustainable excellence in business performance and personal career progression. It may provide a broad sketch of where we stand today in the VUCA world.

The years ahead for pharma won’t be quite the same:

A strong wind of change has already started signaling that the years ahead for the pharma industry, won’t be quite the same as the bygone years nor like what it is today. Some, industry professionals have picked up this cue, while many are still in pursuit of replicating the traditional past with some digital tweaking here and there, whatever may be the reasons.

The current mix of skill sets of the sales and marketing professionals, quite perceptibly, tilts more towards sharpening the softer skills of the employees, as the traditional pharma business models prompt so.

Future need – rebalancing the skill sets:

To be a successful in the days ahead, pharma companies would need to dive deep into the cyberspace – just to be on the same wavelength with its important stakeholders, including, the Government.

Looking around, one witnesses many patients going digital at a faster pace than ever before. They enjoy the cyberspace while embracing the new ways of living life, such as – communicating digitally, chatting in WhatsApp sharing patient’s experience, interacting with online patient communities, and preferring data mining to know more about anything of interest. These activities also get them a sense of the differential advantages of various health care products, services and their cost, before or while consulting doctors and deciding what they can afford.

Similarly, many medical professionals are also not depending solely on the company representatives now to get relevant details on any medicinal product, device or services. Besides frequent interaction with their peer groups, they get such detail information from various websites run by independent, and credible expert groups.

Thus, one of the common arena for pharma stakeholder engagement and interaction would soon be the enigmatic Cyberspace. As the changing days come nearer, there is likely to be greater emphasis on the acquisition of talent having specialized hard skills in this area of sales and marketing.

This emerging scenario prompts rebalancing the mix of soft and hard skill sets with much greater care, and hire young sales and marketing professionals, accordingly to give shape to it. This process should commence now, as the present makes way for the future. This is so important because, the current trend of tweaking with many digital tools and devices mostly as interfaces, or for complementing in-person product detailing or for better field management, or even to draw up marketing and sales plans, may not yield the desired business results any longer, even for survival, as we move on.

Becoming digital natives?

According to the 2015 A.T. Kearney Report titled, “Time for Pharma to Dive into Digital”, pharma sales and marketing professionals must also become digital natives, providing content that is both up-to- date and appropriate for multiple digital channels. Moreover, they will have to be familiar with advanced analytics to monitor and measure actual consumption pattern, besides capturing in real time a huge sample of relevant data for deeper customer insights.

The new normal:

One of the biggest challenges would be in the approach to content development and management. Creating an interactive detailing toolbox for truly responsive customer engagement, requires a good deal of thought and quite complex coding. This would necessitate centralization of marketing content production, which is traditionally decentralized in many sales and marketing organizations. Similarly, the major focus of the sales force will shift from maximizing physician-call rates, to becoming a team of digital communication specialists, and coordinators who would ensure that the right channels are used at the right time.

As the November 2016 Accenture Report titled, ‘The Rebirth of The Pharmaceutical Sales Force’ underscores, the most successful pharmaceutical sales teams in the future will be those willing to define and servicing customers in new ways… and will use digital advances to change the conversation, and position themselves as committed to helping physicians improve health outcomes.

This expected change, I reckon, will put in place a new normal for pharma sales and marketing success in the years ahead.

In conclusion:

Young aspirants wanting to make a career in the pharma industry, may wish to take note of this evolving trend of inevitable changes. They may wish to get well-considered views on the same of a couple of experts’ having no conflict of interest, for a careful and independent personal assessment. These budding strivers should realize that the final actionable decision on developing requisite hard and soft skill sets for a successful take off in their respective working lives, should preferably be taken only by themselves, and none else.

An August 2015 article of McKinsey & Company titled, “The road to digital success in pharma” articulates that the pharma companies, though can play a central role in the digital revolution of healthcare, are running hard to keep pace with changes brought about by digital technology. But soon there may not be any other option left for achieving business excellence.

While the nation is taking strides to transform itself into ‘Digital India’, the pharma companies operating in the country can’t possibly afford to remain far behind. Willy-nilly, they will soon need to realign their business processes accordingly, as there may not be any further scope for individual pharma players to operate within the same old cocoon of tradition bound activities, and still survive.

To meet the new and tougher demands for excellence in pharma sales and marketing, the urgent need of the changing time lies squarely outside the box. To usher in a requisite transformation in the current business model, it calls for a series of well-calibrated, much researched, and bold steps – skillfully rebalancing the crucial soft and hard skill sets, achievable within a realistic and self-determined timeframe.

By: Tapan J. Ray

PILMAN

A Tapan Ray Website

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