Focus On Patient Compliance To Boost Pharma Sales…And More…

One high-impact area in the healthcare space that often finds its place in the backseat is – patient noncompliance. A term that is commonly used in regard to ‘a patient who does not take a prescribed medication or follow a prescribed course of treatment.’ It comes with a steep price, for causing serious adverse impact not just on human health and health system, but also in the pharma business. Intriguingly, such incidents are still not scientifically monitored enough and vigorously acted upon, both globally and locally.

The World Health Organization (W.H.O) has also flagged it as a huge problem, as it reports, 10 percent to 25 percent of hospital and nursing home admissions result from patient noncompliance. Furthermore, about 50 percent of prescriptions filled for chronic diseases are not taken correctly, with 40 percent of patients not adhering to the treatment regimen.

In this article, just after giving a flavor to its financial cost to patients, I shall dwell mostly on its impact on the pharma players, as overcoming this important problem doesn’t generally fall in the area of strategic focus for most of them. Finally, I shall explore how drug manufacturers can translate this problem into an opportunity – as the third growth driver for business, creating a win-win situation for all.

Economic and health impact on patients:

Noncompliant patients suffering from both acute and chronic ailments, pay a heavy price, not just in terms of longer suffering arising out of complications, but also incurring significantly more health expenditure for treatment of the same diseases. According to IMS Institute for Healthcare Informatics, on average, less than 40 percent of patients around the world are fully complying with their treatment instructions.

Even in the Indian context, the problem is no different. Let me illustrate the point with the example of a chronic disease, such as Asthma. The article published on June 26, 2018 in ‘Lung India’ – the official publication of Indian Chest Society reported: “The mean annual direct costs among compliant and non-compliant patients were ₹14, 401 and ₹24, 407, respectively. Percentage of hospitalization was less among the compliant group (6 percent) when compared with noncompliant group (17 percent).”

The study concluded, asthma is not only associated with patient-specific impairment, but also creates a significant economic burden for the family and society. The major contributors to the burden are the medication cost and hospital admissions. Patient compliance with prescribed drugs can help keep asthma under control, thereby decreasing the economic burden and emergency hospital admissions – avoiding the economic risk from ill health with high out of pocket payments.  Productivity loss is another under-appreciated source of economic loss contributing to indirect cost. The rising costs of investigations, interventions, and treatment of chronic diseases further complicate the problem.

Economic impact on pharma business:

According to November 16, 2016 report, published by Capgemini and HealthPrize Technologies, globally, annual pharmaceutical revenue losses had increased from USD 564 billion in 2012 to USD 637 billion due to non-adherence to medications for chronic conditions. This works out to 59 percent of the USD 1.1 trillion in total global pharmaceutical revenue in 2015.

The report highlights, besides medication nonadherence being a serious global health issue that needs to be addressed immediately, it also happens to be a critical business issue for pharmaceutical companies. Thus, it is the only area of their business where a sharp strategic focus “can generate significant top – and bottom-line growth, improve outcomes, and create substantial savings for the healthcare system – all at the same time.”

Major reasons for patient noncompliance:

Several reasons are commonly attributed to patient-noncompliance to medicines, such as:

  • Lack of knowledge of its health and economic impact
  • Importance of completing the full-course of the drug and dosage regimen for long-term remission, following immediate relief
  • Untoward side-effects and other inconvenience
  • Forgetting therapy because of preoccupation
  • Financial inability to complete the prescribed treatment regimen due to the high cost of drugs.

Nevertheless, the 9th Edition of Global Research Report by Capgemini Consulting underscores that reality is more complex. Patient adherence initiatives, if any, when undertaken, even by pharma companies, often lack a thorough understanding of the root causes of discontinuing treatment and failure to effectively engage patients with a holistic approach to the issue. It also emphasizes: “Individual tactics are tried by different brands and then discontinued as budgets and priorities shift, before their impact is known. Successes are seldom pulled through and expanded across the organization.”

Using it as the third major growth drivers for pharma:

The two primary factors that drug manufacturers are leveraging to boost growth of the organization are:

A.  New product introduction – gradually extending to line extensions and new indications. One such illustration is the cholesterol-fighting drugLipitor of Pfizer. The lifetime sales of this brand as of the end third quarter 2017 generated a stunning USD 150.1 billion of business for the company. Incidentally, Lipitor patent expired in 2011. There are many similar examples, including Humira of AbbVie.

B.  Regular and hefty price increases for already marketed products, for various reasons, but almost regularly. According to this 2019 report, percentage price increases, on a huge base, of some of the world’s top pharma brands were as follows:

  • AbbVie: Humira, a blockbuster drug with USD 15 billion in sales in the first 9 months of 2018: +6.2%
  • Allergan: Many of its brand-name drugs, including dry-eye medication Restasis: +9.5%
  • Biogen: Multiple sclerosis drug Tecfidera: + 6%
  • Bristol-Myers Squibb: Eliquis, a drug that prevents blood clots and is on pace for USD 6 billion in sales in 2018: + 6%
  • Eli Lilly: Type 2 diabetes medication Jardiance: + 6%

Many studies have captured the importance of regular price increase, as a key pharma strategy, not only to drive the internal growth, but also to keep their investors, as well as, the stock market on the right side. There are examples that for some of the top global pharma players, this strategy was directly responsible for 100 percent of earnings-per-share growth in 2016, and more than 20 percent of the revenue made in the first three quarters of 2018.

On the other hand, some top analysts’ findings highlight that drug companies serious strategic focus just on the issue of patient noncompliance with novel tactical measures, could fetch as much as a 30 percent increase in annual earnings per share for many players, even in India.

This brings up to the point – can strategic focus to minimize patient’s non-compliance, supported by adequate resources, be the third growth driver for drug companies?

Can focus on patient noncompliance be the third growth driver for pharma?

For a moment, leaving aside the above two primary growth drivers, if we look at the estimates, as quoted above, well over 50 percent to 60 percent of a brand’s potential sales is wasted due to patient noncompliance. Isn’t it huge? Can this be ignored? Obviously not. Instead, why not pharma converts this problem into an opportunity, with a sharp strategic focus, leveraging technology.

Translating this potential opportunity into reality is neither very easy nor is every company’s cup of tea. But the reward for the winners is indeed phenomenal. To chart on this frontier, one of the toughest barriers, besides a winner’s mindset, is getting access to credible and meaningful patient-data, for various reasons. On the other hand, it isn’t an insurmountable problem, either – especially, with today’s rapidly progressing technology.

Some companies have started the long march:

According to the review article, published in the New England Journal of Medicine: ‘The ability of physicians, to recognize non-adherence is poor, and interventions to improve adherence have had mixed results. Furthermore, successful interventions generally are substantially complex and costly.’

Realizing that it as a potential opportunity – disguised as a problem, several pharma players have started thinking about exploring this not much charted territory, confirm reports coming from different countries of the world. To give an illustration, November 22, 2016 edition of Fierce Pharma reported: ‘Pharma companies have more recently joined the conversation with partnerships and programs that include adherence aims.’

It is generally believed today that rapid ascendency of modern technology, and its strong influence on people, will help create a new awareness of its current adverse impact both on patients and the drug companies.

What else could be done in a much wider scale?

Digital interventions, such as smartphone apps, are becoming an increasingly common way to support medication adherence and self-management of chronic conditions. In this regard, the May 14, 2018 study titled, ‘Smartphone apps for improving medication adherence in hypertension: patients’ perspectives’, published in the journal of Patient Preference and Adherence, concluded as follows:

‘These data showed that patients can identify the benefits of a medication reminder and recognize that self-monitoring their blood pressure could be empowering, in terms of their understanding of the condition and interactions with their general practitioners.’ But some loose knots are still to be tightened.

Tightening the loose knots:

Having leveraged the state of the part digital technologies to tighten the loose knots in this area,a host of AI-enabled smartphone health and diagnostic apps, capturing patient compliance details, especially in chronic disease areas, are fast coming up. Most of these are being developed by large, small and medium sized non-pharma pure tech companies, including startups. For example, according to reports: ‘With the release of the Apple Health Record and Apple Watch with a single-lead ECG, it’s evident that Apple has officially entered the healthcare space.’

A good number of these apps have received even the US-FDA approval, such as: MyDose Coach - a reliable dose calculating app for type 2 diabetic patients who take insulin once-daily in concert with physician guided insulin recommendations. Or, GoSpiro – a home spirometer, to measure air output from the lungs for COPD patients and connects wirelessly to provide hospital-quality data regarding breathing.

That many non-pharma entities are trying to create a space for themselves in a high-tech, but non-drug treatment segment within the pharma space, has prompted, several drug manufacturers to rewrite their marketing playbook, incorporating this ‘new notation’.

It’s real now…for some:

As the above Fierce Pharma article reported: ‘Pharma companies have more recently joined the conversation with partnerships and programs that include adherence aims; efforts from Verily and Sanofi and IBM and Novo Nordisk have recently made the news.’Further, on November 07, 2018, in another report it brings to the fore that Geisinger Health System has developed mobile apps to manage asthma with AstraZeneca, and a wearable app to manage pain with Purdue. It also joined forces with Merck to develop tools for patients and caregivers to improve care coordination and medication adherence.

Moreover, on February 09, 2019, Japanese drug major Astellas and WiserCare - a company that develops healthcare decision support solutions, announced a collaboration that includes improving patient adherence to care plans, and improve the overall care experience.

In tandem, concern on patients’ data privacy, may also now be addressed, possibly by making use of blockchain or similar technology for such initiatives, as I discussed earlier in this blog.

Conclusion:

‘Acquiring new customers is important, but retaining them accelerates profitable growth,’ is the theme of an article, published in Forbes on June 08, 2016. Therefore, just as any other business, this dictum applies to the pharma industry, as well, especially in context of patient noncompliance to medicines, with a clear strategic focus to minimize its impact on performance.

The major reasons for patient noncompliance ranges from ignorance of its adverse impact on health to side effects, forgetfulness and right up to inability to afford full-course of the prescribed drug treatment. Despite its continuity over decades, adversely impacting patients, health system and the pharma players, it won’t be prudent to infer that no attempt was being made in the past, to address this critical issue. Nevertheless, those measures have not worked, for many reasons, as we see today from various research studies in this area, even in the Indian context.

Once again, intervention of technology to make patients compliant to medicine, is showing promise for following it up more vigorously. That some global drug majors are entering into collaborative arrangements with non-pharma, technology companies of various sizes, sends a signal of the emergence of a third major growth driver for pharma, as discussed above.

This issue is so important, especially considering that the low hanging fruits of R&D have mostly been plucked, just as regular hefty increases of drug prices are meeting with tough resistance, squarely. In this scenario, a robust strategic focus on patient compliance would not only boost pharma sales but would also reduce the disease burden of a large section of people significantly. This will benefit all and harm – none.

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.

India needs ‘Orphan Drugs Act (ODA)’ to counter growing threat of dreaded rare diseases and simultaneously boost global growth potential of the Indian Pharmaceutical Industry

An orphan disease is a rare and uncommon disease and an ‘Orphan Drug’ is a pharmaceutical substance that has been developed to treat an orphan disease. The US FDA defines a rare disease, with a prevalence of 1 in 5,000 of the general population, whereas in the European Union (EU) defines it as a disease with a prevalence of 5 in 10,000 of the population.

Around 6-8% of the world population is manifested by such rare diseases. There are around 5000 of reported rare diseases with an ascending growth trend.

Despite such trend, high drug development cost coupled with low return on investment, do not encourage many innovator pharmaceutical companies to get engaged in R&D initiatives for such drugs. However, this perception is fast changing, as we shall see below.

US took the first step to encourage commercialization of ‘Orphan Drugs’:

Public awareness drives for ‘Orphan Diseases’ first originated in the USA with the formation of a rare disease support group representing around 200,000 patients suffering from such diseases. This awareness campaign ultimately culminated into a path breaking legislation in the US named, ‘Orphan Drugs Act’ (ODA), in 1983. The key purpose of ODA was to incentivize initiatives towards development of such drugs to treat around 25 million Americans suffering from ‘Orphan diseases’. The incentives included:

- Funding towards investigation for “Orphan Disease’ treatment
- Tax credit for Clinical Research
- Waiver of fees for New Drug Application (NDA)
- Offering more lucrative incentive than product patent (product patent requires the drug to be novel), as the orphan designation of the product by the US FDA and product approval by them are the only requirements for 7 year market exclusivity of an ‘Orphan Drug’ for the same indication.
- Market exclusivity of ‘Orphan Drugs’ become effective from the date of regulatory approval, unlike product patent, product development time remains outside this period.
- The drugs, which are not eligible for product patent, may be eligible for market exclusivity as an ‘Orphan Drug’ by the US-FDA

Thanks to this Act, currently around 230 ‘Orphan Drugs’ are available in the US for the treatment of around 11 million patients suffering from rare diseases. With the help of ‘Human Genome Project’ more orphan diseases are expected to be identified and newer drugs will be required to treat these rare ailments of human population.

1983 signaled the importance of ‘Orphan Drugs’ with the ODA in the US. 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.

India needs ODA:

Unfortunately in India, we do not have any ODA, as of now. Such legislation could give a new fillip to the Indian Pharmaceutical and Bio-Pharmaceutical industry and at the same time usher in a new hope to thousands of patients suffering from rare diseases in India, with the availability of relatively lower cost medications to them.

The global market:

The global market of ‘Orphan Drugs’ is expected to grow to US $ 112 billion in 2014 from US $85 billion in 2009. Biotech products contribute around 70% of this turnover with relatively higher CAGR growth rate of around 7%. However, reluctance of the insurance companies to cover ‘Orphan Drugs’ due to higher price still remains a global issue.

Orphan drugs to create a paradigm shift in the Pharmaceutical Industry: says Frost & Sullivan:

“While the pharmaceutical industries have been focusing on ‘blockbuster’ small molecules (chemical drugs) for high revenue generation in the past, it is expected that in 5 years, around $90.0 billion worth of branded drugs will lose their exclusivity. The current economic situation plus the huge generic competition shifted the focus of pharmaceutical companies and they are moving to a new business model – ‘Niche busters’, also called Orphan drugs.”

It is believed that Orphan drugs will now offer an attractive opportunity to the pharmaceutical companies than ever before to significantly absorb the impact of the ‘Patent Cliff’. Various financial incentives provided by the governments of various countries under the ODA coupled with many smaller collaborative projects towards this direction will further encourage the global pharmaceutical players to develop ‘Orphan Drugs.

Currently, EU has granted over 700 ‘Orphan Designations’ and over 60 new drugs have received favorable response for Market Authorization.

Sales potential for ‘Orphan Drugs’:

Generally ‘Orphan Drugs’ were not expected to be very high revenue earners. However, about 4 year ago in the year 2006, about 50 ‘Orphan Drugs’ were reported to had crossed a sales turnover of US $200 million. In 2006 the following ‘Orphan Drugs’ with expired market Exclusivity in the US, had assumed blockbuster status:

- Enbrel (Immunex): US $ 4.38 billion
- Rituxan (Genentech): US$ 3.97 billion
- Nupogen/Neulasta (Amgen): US $ 3.92 billion
- Epogen (Amgen): US $ 2.50 billion
- Avonex (Biogen): US $ 1.70 billion
- Betaseron (Novartis & Bayer): US $ 1.33 billion
- Intron A/ PEG-Intron (Schering): US $ 1.07 billion
- Kogenate (Bayer): US $ 1.07 billion
- Ceredase/Cerezyme (Genzyme): US $ 1.00 billion

Key growth drivers for ‘Orphan Drugs’:

In my view the following key factors will play critical role in driving the growth for ‘Orphan Drugs’:

- Market exclusivity options for a number of FDA recognized ‘Orphan Indications’ for the same drug
- Market exclusivity for seven years in the U.S. and ten years in the EU for each of the ‘Orphan Indications’
- Oncology could be a good segment to get such multiple ‘Orphan Indications’ for the same molecule

Glivec of Novartis obtained approval for around five new ‘Orphan Indications’, the key indications being Chronic Myelogenous Leukemia (CML) and Gastrointestinal Stomal Tumors. The product has already assumed a global blockbuster status with an estimated sales turnover of over US $4 billion by 2011.

Biotech companies are champions for the development of ‘Orphan Drugs’, globally:

Since long, the Biotech companies are taking initiatives for the development of ‘Orphan Drugs’. The path breaker in this respect was Genentech of the US, which developed two growth hormone molecules with names Protophin and Nutrophin, way back in 1985. Now, having realized the hidden potential of this segment more number of pharmaceutical players are entering into this arena. Thus, it is no wonder that 13 out of 19 blockbuster ‘Orphan Drugs’ were biologics in the year 2006.

Conclusion:

It is interesting to note that some of the ‘orphan diseases’ are now being diagnosed in India, as well. As India takes rapid strides in the medical science, more of such ‘Orphan Diseases’ are likely to be known in our country. Thus the moot question is how does India address this issue with pro-active measures?
Currently, India is curving out a strong niche for itself in the space of biogenerics. Pfizer-Biocon deal will vindicate this point.

Moreover, with Pharmacogenomics keep gaining ground at a faster pace, as I mentioned earlier, there will be a shift towards personalized medicines, in not too distant future, in which case the blockbuster drugs as defined today, will be effective only for a smaller number of patients. If the Government of India visualizes this scenario sooner, and comes out with appropriate ODA for the country, domestic pharmaceutical industry of India, in general and biopharmaceuticals industry of the country, in particular, will be able emerge as a force to reckon with, in this important global space, much faster than what one would currently anticipate.

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.