Monthly Archives: December 2017

Health Care in India And ‘Development For All’ Intent

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‘Development for All’ has become a buzzword, especially in the political arena of India, and is being used frequently during all recent elections as no one can deny its crucial importance in a country like ours.

Nonetheless, some do feel that there should be greater clarity on what all it encompasses. There is no scope for assumption, either, that it definitely covers the economic growth of the nation. But, does it include health care for all, as well? This is a relevant question, since health care plays a crucial role in maintaining high growth of Gross Domestic Product (GDP) by any country, over a long period of time.

The ideal answer to this question would, of course, be an emphatic ‘yes’? However, on the ground is it really so? I explored that subject in my article published in this Blog on November 06, 2017 titled, ‘Healthcare in India And Hierarchy of Needs’.

In this article, I shall focus on health care and the ‘Development for All’ agenda of the Government, as witnessed by many in recent elections. Let me illustrate the point using one of the most recent state assembly elections as an example – Gujarat Assembly election of December 2017. I am citing this example, because it generated so much excitement among many, across the country, for different reasons, though.

Who is responsible for public health care in India?

A recent submission made on the floor of Parliament by the Government, explains the point unambiguously. It goes, as hereunder:

“Public health is a state subject. Under the National Health Mission, support is being provided to States/UTs to strengthen their health care systems to provide accessible, affordable and quality health care to all the citizens. Moving towards Universal Health Coverage wherein people are able to use quality health services that they need without suffering financial hardship is a key goal of 12th Plan.” This is what the Minister of State, Health and Family Welfare, reiterated in the Lok Sabha, just about a year ago, on November 25, 2016.

Since, public health is predominantly a state subject, and so important for each individual, besides being one of the key indicators for long-term socioeconomic progress of a country and, one expects health care to be a key issue during the state Assembly elections. This is necessary to maintain the pace of development in this area, be it a state or the country.

Intriguingly, it appears to have no more than a ‘me-too’ reference in the election manifestos of political parties.

Does health care scenario in a state matter?

Now, zeroing on to Gujarat election as an example, the media report of March, 2017 highlighted, gradually reducing budget allocation percentage of health care in Gujarat. It elaborated, the State has reduced its budgetary allocation for health care from 5.59 percent of the total budget in 2015-16 to 5.40 percent of the revised budget of 2016-17, and now to 5.06 percent in 2017-18.

Consequently, the health care budget and spending on the proportion to the Gross State Domestic Product (GSDP) is going down year after year. Whereas, globally, the percentage of GSDP spent on health and education is considered a key parameter of human development, the report states.

According to a report of the Observer Research Foundation dated December 06, 2017, Gujarat still has a high dependency to the private sector for both outpatient (84.9 percent cases) and also the inpatient (73.8 percent cases). As a result, the out of pocket spending on health care of the state stands at 63.7 percent. This makes Gujarat climbing up the ladder of per capita income, while slipping down the slope of health and social indicators,” the article states.

Just as what happens in all other Indian states, the recent state assembly elections offered an opportunity for the political leadership, cutting across the party line, for a significant course correction. Making health and nutrition one of the top priority focus areas, would have also ensured sustain economic development for Gujarat, in a more inclusive manner, for a long time to come.

What we are witnessing, instead:

The ‘best’ intent of a political party on any area of governance, if it comes to power, generally gets reflected in the respective election manifestos. From that perspective, let’s take a quick look at the key promises on health care, made in the respective election manifestos of the two principal political parties, on the eve of December 2017Gujarat election. I found these, as follows:

Key highlights on health care in BJP Manifesto:

  • The party promised to open more generic medicine shops
  • Introduce mobile clinics and laboratories
  • Making Gujarat free of vector-borne diseases.

Key highlights on health care in Congress Manifesto:

  • Universal health care card

That’s all?… Yes, that’s it.

India is ‘developing’, but public health care is not:

‘The Lancet’ editorial titled, ‘Health in India, 2017’, published on January 14, 2017, discussed about the current status of public health care in India. It underscored that the government expenditure on health being one of the lowest in the world at 1·4 percent of GDP, is totally inadequate to train staff, buy necessary equipment, or efficiently run public health facilities.

Corruption and an unregulated private sector usually fill this vacuum, and in so doing, fuel irresponsible prescribing, and global export of antimicrobial resistance, besides misery and medical bankruptcy for those within the country, lacking financial protection.

The editor articulated that the solution of this important issue is clear. Publicly financed Universal Health Coverage (UHC) has not only been deliberated in India since the dawn of the nation, but has also been highly recommended by both the domestic and the external stakeholders.

Nevertheless, successive governments seem to be lacking either the spine or the heart to act. As recently as 2011, progressive universalism was included in the government’s 5-year plan, but was never funded – the editorial commented.

Both the States, and also the national election campaigns, offer an opportunity for the politicians who the prospective lawmakers, to steer the States, and in that process the country as a whole, moving towards the UHC.

Conclusion:

As heath is a state subject, the issue of providing access to high quality and affordable health care to all should ideally become one of the core issues for all voters, at least, in the State Assembly elections. More so when the sound bite on ‘development for all’ reaches a feverish pitch. There can’t be any holistic ‘development for all’, sans health care and education.

Nonetheless, the reality is, unlike the United States, Europe or Japan, besides a few other countries, the voters in India are also not expressing their concerns in this area, meaningfully. In all probability, ‘development for all’ slogan of the politicians doesn’t include health care to all Indians.

This is likely to continue, in the same way, till the awareness of the socioeconomic impact on health care carves out a niche for itself in the popular political agenda for the voters. Just as what happens with many other economic, technological necessities and other aspirations of people. The recent assembly elections are important pointers to this long persisting trend.

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.

SCM: Embracing Technology For Patients’ Safety

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Supply Chain Management (SCM) in the pharma industry is generally perceived as a logistic function, just in most other industries, involving the distribution of medicines from manufacturing plants, right up to pharma distributors. Thereafter, it becomes the responsibility of the respective distributors to reach these to the wholesalers, who cater to the needs and demand of retail chemists.

In tandem, pharma SCM is also playing a key role in reducing overall cost of drugs, improving the profit margin, and to some extent their affordability to a larger number of patients. This process involves efficient procurement of right products of the right quality, transporting them in the right condition, delivering them at the right location in right time, with optimal inventory carrying cost.

That said, today’s reality demands the SCM to cover much larger space. This calls for taking in its fold even those critical parameters that go beyond the realm of business performance – protecting the health and safety interests of patients, effectively. In that sense, SCM plays a pivotal role pharma business operation, having a potential to make a profound impact in the lives of many, quietly.

Coming out of the cocoon of narrowly defined distribution or logistic functions, pharma SCM, in many countries, has started rediscovering itself, as a multi-dimensional and multi-factorial business necessity, keeping patients within its core focus area, always.

I wrote on ‘The importance of Supply Chain Integrity’ and ‘Maximizing value of a new product launch with an innovative Supply Chain Management System’ in this blog on November 29, 2010 and August 30, 2010, respectively. Thus, in this article, I shall dwell on the role of pharma SCM in ensuring patients’ health and safety, embracing modern technology.

Current concerns:

Gradual transformation of SCM with high-tech interventions is visible now, but in a sporadic way. Speedy development initiatives in this area need to be more inclusive, everywhere. This is a paramount requirement of the pharma business, that has been prompted by serious breaches in the SCM process, affecting patients’ health, safety and security, besides impacting the brand image.

Manifestations of these get reflected in the instances like, availability of substandard and counterfeit drugs, or large product recalls, or quality issues with APIs and excipients escaping SCM scrutiny.

W.H.O says, it’s now all-pervasive:

The availability of substandard and falsified medical products, although is a menace to the society, seems to be all pervasive. The November 2017, Fact Sheet of the World Health Organization (W.H.O) recognizes this fact. The paper categorically states that no country has remained untouched by this issue – from North America and Europe to sub-Saharan Africa, South East Asia, and Latin America. Thus, this hazard, once considered a problem limited to developing and low-income countries, is no longer so.

The leading factors: ‘poor governance and weak technical capacity’:

The W.H.O study titled “Public health and socioeconomic impact of substandard and falsified medical products” released in November 2017 invited rather embarrassing media headlines, such as “India among countries where 10% of drugs are substandard.” Some of the most common medicines consumed in India, such as Combiflam and D-Cold were also found as sub-standard by Central Drugs Standard Control Organization (CDSCO) – as this news item reports.

Commenting on the possible reasons for this menace, W.H.O underscored that such substandard and falsified medical products are most likely to reach patients in 3 important situations. These are, constrained access to high quality and safe medical products, poor governance, and weak technical capacity.

The most important and viable option to effectively address this drug-safety threats is innovative applications of state of the art technology platforms. Many pharma players, are gradually realizing it through experience. Quite in unison, various Governments, India included, are also contemplating to follow the same path. Some nations are enacting robust laws for strict compliance of the remedial measures, as charted out by the respective drug authorities.

Harnessing technology as an enabler:

I reckon, harnessing modern technology will facilitate putting in place a robust ‘Track and Trace’ in the SCM, through product ‘serialization’, to effectively address this menace. As many would know, pharma serialization broadly means that each medicinal product pack will carry a Unique Identifier (UID), that can be tracked and traced till the same reaches the end-user.

The process may start with the key ‘touch points’ of a drug before it reaches the patients, such as suppliers, formulators, carrying and forwarding agents (C&FA) or distributors, wholesalers and retailers. This can be extended backwards, as well, to make the drug-sourcing process safer, which is also of crucial importance.

Leveraging technology for patient safety:

Realizing the importance of drug-safety needs of patients, many drug regulators, even in the developed markets, are leveraging technology as a key enabler in the SCM value chain to effectively address this issue. There are several recent global examples of achieving this specific objective. One such example comes from the top pharma market in the world – the United States.

Where the ‘Track and Trace System’ came as a law:

To ensure greater drug-safety for patients in the country, the oldest democracy of the world decided to introduce the ‘Track and Trace System’ in the SCM process by enacting a robust law. Accordingly, in December 2016, the US-FDA released the final guidance on the implementation of the Drug Supply Chain Security Act (DSCSA).

Under this law an electronic ‘Track and Trace System’, through product ‘serialization’, will be put in place in the United States. As reported in the ‘Pharmacy Times’, DSCSA comes into force to regulate transactions between dispensers, pharmacies, and also among manufacturers, repackagers, wholesale distributors, third-party logistics providers, and trading partners, from November 24, 2017.

Following DSCSA, on June 30, 2017, the agency issued a draft guidance for the industry, titled Product Identifier Requirements Under the Drug Supply Chain Security Act – Compliance Policy. It informed the manufacturers and other supply chain stakeholders that “although manufacturers are to begin including a ‘product identifier’ on prescription drug packages and cases on November 27, 2017, the FDA is delaying enforcement of those requirements until November 2018 to provide manufacturers additional time and avoid supply disruptions.”

The US-FDA explains ‘product identifier’, as follows:

  • A unique identity for individual prescription drug packages and cases, which will allow trading partners to easily trace drug packages as they move through the supply chain.
  • Includes the product’s lot number, expiration date, a national drug code (or NDC), and a serial number. The serial number is different for each package or case. This creates a unique identifier – human and machine readable – to enable product tracing throughout the supply chain and enable all trading partners to better detect illegitimate products within the supply chain.

The US drug regulator clarified that the compliance policy outlined in the draft guidance applies solely to products without a product identifier that are introduced into commerce by a manufacturer between November 27, 2017 and November 26, 2018.

Several other countries also realizing its criticality:

Besides the United States, several other countries are harnessing high technology to make the SCM system more robust to ensure patient safety. Some of these include, EU, South Korea, Brazil and China, South Korea and Argentina. India too has initiated action in this area, but only for exports, as on date. Intriguingly, drug-safety for patients within the country doesn’t seem to be on the ‘must do’ list of the law and policy makers of the country, just yet.

‘Track and Trace’ system in India:

As stated above, the ‘Track and Trace’ system in India for drugs is currently applicable only to pharma exports. By a notification dated January 05, 2016, the Directorate General of Foreign Trade (DGFT) made encoding and printing of unique numbers and bar codes as per GSI Global Standard mandatory. This would cover tertiary, secondary and primary packaging for all pharmaceuticals manufactured in India and exported out of the country to facilitate tracking and tracing.

However, for drugs in the domestic market, although a draft proposal was circulated to the stakeholders in June 2015, but no significant progress has yet been made on its implementation in India.

Conclusion:

Availability of potentially harmful substandard and counterfeit drugs is posing a threat to public health and safety, almost in all countries across the world, with a varying degree, though. The November 2017, Fact Sheet of the World Health Organization (W.H.O) also highlighted this issue with a great concern.

A robust SCM systems, built on modern technological platforms are now receiving encouragement from the Governments in many countries, to contain this menace. Accordingly, lawmakers are formulating tough laws, and the drug regulators are specifying the requirements that need to be built into the pharma SCM mechanism.

Some pharma players, on their own, are further raising this bar, while framing their internal compliance norms for SCM. They realize that besides responding to patients’ health and safety needs, it is necessary for the commercial consideration too, alongside the company’s reputation.

Although, India is included among those countries where 10 percent of drugs are substandard, as the W.H.O reports, no such regulatory mechanism has been made mandatory within the Supply Chain to cover drugs in the domestic market, as yet. Interestingly, the DGFT has made the ‘Track and Trace’ mechanism only for the exporters, probably for patients’ health safety of the importing countries! Neither has the majority of domestic pharma manufacturers voluntarily implemented it, demonstrating ‘Patient-Centricity’.

Making SCM robust, weaving into it the drug-safety needs of patients, is a necessity in India too. When a large number of countries, including BRICS nations, are embracing modern technology to achieve this goal, why isn’t India doing so – intriguing…No…?

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.

 

Leveraging Artificial Intelligence For Greater Patient-Centricity

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‘Artificial Intelligence (AI)’ – the science of simulation of intelligent behavior in computers, has the potential to leave a transformational impact on virtually everything that we see and feel around us. As many will know, the modern definition of AI is “the study and design of intelligent agents where an intelligent agent is a system that perceives its environment and takes actions which maximizes its chances of success.”

Let me begin with a couple of exciting examples on the application of AI for general use. One such is Siri the voice-activated computer in the iPhone that one can interact with as a personal assistant, every day. The other is the self-driving features with the predictive capabilities of Tesla cars; or even the well-hyped Google driver-less car. Alongside, Google is also in pursuit of creating AI with ‘imagination’ through its ‘DeepMind’. It develops algorithms that simulate the human ability to construct plans.

Pharma’s emergence in the AI space:

The unfathomable potential of AI is being slowly recognized in the healthcare arena, as well, including pharma industry. It’s gradual emergence in the space of ‘intelligent learning’, often called ‘machine learning’, ushers in a new paradigm of learning from a vast pool of highly credible real-time data. Innovative applications of this process can fetch a game changing business performance. Its scope spans right across the pharma value chain – from Drug Discovery, including Precision Medicine; Clinical Trials; Pharmacovigilance; Supply Chain Management, and right up-to Sales and Marketing.

Pharma’s emergence in the AI space is quite evident from Reuters report of July 3, 2017. It wrote that GlaxoSmithKline (GSK) has inked a new USD 43 million deal with Exscientia to help streamline the company’s drug discovery process by leveraging AI. With this deal in place, Exscientia will allow GSK to search for drug candidates for up to 10 disease-related targets. GSK will provide research funding and make this payment, if pre-clinical milestones are met.

Again, on July 27, 2017, Insilico Medicine – a Baltimore-based leader in AI, focusing on drug discovery and biomarker development, announced a similar agreement with the biotechnology player Juvenescence AI Limited. According to this agreement, Juvenescence AI will develop the first compounds generated by Insilico’s AI techniques, such as Generative Adversarial Networks in order to generate novel compounds with desired pharmacokinetic and pharmacodynamic properties.

Several other pharmaceutical giants, including Merck & Co, Johnson & Johnson and Sanofi are also exploring the potential of AI for streamlining the drug discovery process. It would help them to significantly improving upon the hit-and-miss business of finding new medicines, as Reuters highlighted.  Eventually, these applications of AI may be placed right at the front-line of pharma business – in search of new drugs.

I have already discussed in this blog – the ‘Relevance of AI in creative pharma marketing’ on October 31, 2016. In this article, I shall mainly focus on leveraging AI in health care for greater patient-centricity, which is emerging as one of the prime requirements for excellence in the pharma business.

Imbibing patient-centricity is no longer an option:

In an article published in this blog on the above subject, I wrote that: ‘providing adequate knowledge, skills and related services to people effectively, making them understand various disease management and alternative treatment measures, thereby facilitating them to be an integral part of their health care related interventions, for better health outcomes, are no longer options for pharma companies.’

The craft of being ‘patient-centric’, therefore, assumes the importance of a cutting-edge  of pharma business for sustainable performance.

What exactly is ‘patient-centricity’?

BMJ Innovations – a peer reviewed online journal, in an article titled, ‘Defining patient centricity with patients for patients and caregivers: a collaborative endeavor’, published on March 24, 2017, defines ‘patient-centricity’ as: “Putting the patient first in an open and sustained engagement of patient to respectfully and compassionately achieve the best experience and outcome for that person and their family.”

Thus, to deliver the best experience, and treatment outcomes to patients, their participation and engagement, especially with the doctors, hospitals and the drug companies assume significant importance.

The June 2017 ‘Discussion Paper’ of McKinsey Global Institute, titled ‘Artificial Intelligence the Next Digital Frontier’ also captured this emerging scenario, succinctly. Recognizing that health care is a promising market for AI, the paper highlighted the enormous potential in its ability. The power of which can draw inferences by recognizing patterns in large volumes of patient histories, medical images, epidemiological statistics, and other data.

Thus, AI has the potential to help doctors improve their diagnoses, forecast the spread of diseases, and customize treatments. Combined with health care digitization, AI can also allow providers to monitor or diagnose patients remotely, as well as transform the way we treat the chronic diseases that account for a large share of health care budgets, the paper underscored. This poses the obvious question: what exactly AI can possibly do in the space of health care?

What can AI do for health care?

In a nutshell, the application of AI or ‘machine learning’ system in health care generally uses algorithms and software to approximate human cognition in the analysis of relevant, yet complex scientific and medical data. In-depth study and interpretation of these in a holistic way would be of immense use in many areas. For example, to understand the relationships between prevention or treatment processes and outcomes, or various debilitating conditions affecting people with the advancement of age, to name just a few.

This necessitates the generation of a huge pool of relevant and credible data from multiple sources, storing and analyzing them meaningfully, and then garnering the capabilities of ‘machine learning’ with the application of AI. Such a process helps in zeroing-in to a series of complex, interdependent strategic actions to go for the gold, in terms of business results. Using conventional methods, as exist today, other than imbibing AI or ‘machine learning’, may indeed be a Herculean task, as it were, to achieve the same.

Invaluable business insights thus acquired need to be shared, across the various different functions of a company, for greater patient-centricity within the organization.

Moving from ‘patient-engagement’ to ‘patient-centricity’:

While making a significant move from just ‘patient engagement’ to being ‘patient centric’, one-size-fits-all strategy is unlikely to yield the desired results. The process of gathering adequate knowledge and understanding of any individual’s disease management skills, which mostly depend on complex multi-factorial, interrelated and combinatorial algorithms, will be a challenging task, otherwise.

Thereafter, comes the need to deliver such knowledge-based value offerings to target patients for better health outcomes, which won’t be easy, either, in the prevailing environment.

Considering these, AI seems to have an immense potential in this area. Some global pharma players are also realizing it. For example, GSK is reportedly engaged with IBM’s Watson in the development of AI-enabled interactive digital Apps for its cold and flu medication to provide relevant information to patients.

Conclusion:

Patient-centricity would soon be the name of the game for pharma business excellence. However, to be truly patient-centric, especially in the sales and marketing operations, pharma players would require to source, process and analyze a huge volume of relevant data in several important areas. These include, target patients, target doctors, environmental dynamics, demographic variations, regulatory requirements, current practices, competitive activities, to name a few.

In this strategic business process, AI or ‘machine learning’ will help accurately mapping the ongoing dynamics and trends in virtually all critical areas. It will help ferret out the nuances of turning around the competitive tide, if any, and that too with immaculate precision. In that sense, AI is likely to emerge as a game changer in imbibing patient-centricity, in the real sense. Consequently, it carries a promise of delivering significantly better outcomes, yielding higher financial returns, alongside.

Although, some concerns on AI are being expressed by several eminent experts, it is generally believed that on the balance of probability, it’s crucial potential benefits far outweigh the anticipated risks. In my view, this holds good even for the pharma industry, especially while leveraging AI for greater patient-centricity, better disease prevention, and more desirable treatment outcomes – improving the quality of life of many, significantly.

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.

 

Patent Expiry No Longer End of The Road

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Who says that the phenomenal success of blockbuster drugs is mostly eaten away by  ‘look-alikes’ of the same, immediately after respective patent expiry? It doesn’t seem to be so any longer, not anymore! Several examples will vindicate this emerging trend. However, I shall quote just a few of these from the published reports.

In 2016, the patent of AbbVie’s Humira (Adalimumab), indicated in the treatment of autoimmune diseases and moderate to severely active rheumatoid arthritis, expired in the United States (US). It will also expire in Europe by 2018. This event was expected to create significant opportunities for lower priced Adalimumab biosimilars in the US market, increasing the product access to many more patients at affordable prices. Just as it happens with patent expiry of small molecule blockbuster drugs. One of the classic examples of which, is a sharp decline in sales turnover and profit from Pfizer’s Lipitor (Atorvastatin), as its patent expired on November 30, 2011.

However, Humira topped the prescription-drug list of 2016 with an annual growth of 15 percent, accounting for USD 16 billion sales, globally. More interestingly, according to a recent report of EvaluatePharma, AbbVie’s Humira will continue to retain its top most ranking in 2020 with expected sales of USD 13.9 billion. Nevertheless, possible threat from biosimilars has slightly slowed down its growth. Although, there are many other similar examples, I would quote just three more of these to illustrate the point, as follows:

  • Rituxan (Rituximab, MabThera) indicated in the treatment of cancer and co-marketed by Biogen and Roche, went off-patent in 2015. However, in 2016, the product held 4th position in the prescription drug market with a revenue growth of nearly 3 percent. Even five years after its patent expiry, Rituxan is still expected to occupy the 17th rank with an estimated turnover of over USD 5 billion in 2020, according to the EvaluatePharma report.
  • Remicade (Infliximab) indicated for autoimmune diseases and manufactured by J&J and Merck, lost market exclusivity in 2015. But, in 2016 it still held 5th place in the global ranking. Five years after it goes off patent, Remicade is expected to feature in the 6th rank in 2020, with an estimated turnover of over USD 6.5 billion, according to the same report as above.
  • The US product patent for Lantus – a long-acting human insulin analog manufactured by Sanofi, expired in August 2014. However, in 2016, clocking a global turnover of USD 6.05 billion, Lantus still ranked 10 in the global prescription brand league table. Six years after its patent expiry – in 2020, Lantus will continue to feature in the rank 20, as the same EvaluatePharma report estimates.

These examples give a feel that unlike small molecule blockbuster drugs, patent expiry is still not end of the road to retain this status for most large molecule biologics, across the world. In this article, I shall discuss this point taking Humira as the case study.

What about biosimilar competition?

In any way, this does not mean that related biosimilars are not getting regulatory approval in the global markets, post-patent expiry of original biologic drugs, including the United States. Nonetheless, biosimilar makers are facing new challenges in this endeavor, some of which are highly cost intensive, creating tough hurdles to make such drugs available to more patients at an affordable price, soon enough. It happened for the very first biosimilar to Humira, as well. On September 23, 2016, almost immediately after its patent expiry in 2016, the USFDA by a Press Release announced approval for the first biosimilar to Humira (adalimumab). This was Amgen’s Amjevita (adalimumab-atto), indicated for multiple inflammatory diseases.

The second biosimilar to AbbVie’s Humira – Boehringer Ingelheim’s Cyltezo (adalimumab-adbm), was also approved by the USFDA in August 2017. So far, six biosimilars have been introduced in the United states. But, none of these got approved as an ‘interchangeable’ product. Some of these, such as Cyltezo could not even be launched, as yet. I shall discuss this point later in this article. Thus, Humira is expected to retain its top global prescription brand ranking in 2020 – over 4 years after its patent expiry.

In Europe, two marketing authorizations were reportedly granted by the European Commission (EC) in March 2017 for Amgen’s biosimilars to Humira, named Amgevita (adalimumab) and Solymbic (adalimumab). Later this year, in November 2017 Boehringer Ingelheim’s – Cyltezo also received its European marketing approval.

It is worth noting that in December 2014, the Drug Controller General of India (DCGI) reportedly granted marketing approval for Zydus Cadila’s Adalimumab biosimilar (Exemptia) for treating rheumatoid arthritis and other autoimmune disorders in India. The company claims: “This novel non-infringing process for Adalimumab Biosimilar and a novel non-infringing formulation have been researched, developed and produced by scientists at the Zydus Research Centre. The biosimilar is the first to be launched by any company in the world and is a ‘fingerprint match’ with the originator in terms of safety, purity and potency of the product.”

Several important reasons indicate why a full throttle competition is lacking in the  biosimilar market early enough – immediately after patent expiry of original biologic molecules. I shall cite just a couple of these examples to illustrate the point. One is related to aggressive brand protection, creating a labyrinth of patents having different expiry dates. And the other is a regulatory barrier in the form of drug ‘interchangeability’ condition, between the original biologic and related biosimilars:

In the labyrinth of patents:

The most recent example of innovator companies fiercely protecting their original biologic from the biosimilar competition by creating a labyrinth of patents is Boehringer Ingelheim’s Cyltezo. This is biosimilar to AbbVie’s Humira, approved by the USFDA and EC in August 2017 and November 2017, respectively.

According to reports: “BI does not intend to make the drug commercially available in Europe until the respective SPC (supplementary protection certificate) for adalimumab, which extends the duration of certain rights associated with a patent, expires in October 2018. Cyltezo is also not yet available in the US despite its approval there in August, because of ongoing patent litigation with AbbVie. AbbVie reportedly holds more than 100 patents on Humira, and believes that Boehringer could infringe 74 of these with the launch of its biosimilar. Similarly, the firm has also taken Amgen to court to block the launch of its proposed Humira biosimilar.”

Another interesting example is the epoch-making breast cancer targeted therapy Trastuzumab (Herceptin of Roche/Genentech). The patent on Herceptin reportedly expired in 2014 in Europe and will expire in the United States in 2019. The brand registered a turnover of USD 2.5 billion in 2016. However, a November 21, 2017 report says that creating a series of hurdle in the way of Pfizer’s introduction to Herceptin biosimilar, Roche has sued Pfizer for infringement of 40 patents of its blockbuster breast cancer drug. Pfizer hasn’t yet won approval for its Herceptin biosimilar, though, USFDA accepted its application in August 2017 – the report highlights

‘Interchangeability’ condition for biosimilars:

In the largest global pharma market – the United States, USFDA classifies biosimilars into two very distinct categories:

  • Biosimilars that are “expected to produce the same clinical result as the reference product”
  • Biosimilars that are “interchangeable,” or able to be switched with their reference product

According to reports, experts’ argument over ‘interchangeability’ in the US range from “whether pharmacists should be allowed to switch a biologic for its biosimilar without a doctor’s notification, to whether interchangeable biosimilars might be perceived as better or safer than their non-interchangeable counterparts.” This debate has somewhat been resolved by the US Food and Drug Administration’s (FDA) issuance of draft guidance in January 2017, specifying what should be submitted to support an interchangeable application, the report says.

The article also indicates, “the draft makes clear that switching studies to help gain this designation should evaluate changes in treatment that result in two or more alternating exposures (switch intervals) to the proposed interchangeable product and to the reference product. Study design, types of data and other considerations are also included in that draft.” Nonetheless, compliance with this regulatory requirement is expected to be highly cost intensive, too.

Quoting a senior USFDA official, a report dated June 26, 2017 mentioned: “interchangeable biosimilars will come to market within the next two years, though possibly sooner. And the first interchangeable biosimilar will likely be reviewed by an FDA advisory committee of outside experts.” Still the bottom line remains no biosimilar has yet been approved by the USFDA as ‘interchangeable’. Hence, the optics related to desirable success for biosimilars continue to remain somewhat apprehensive, I reckon.

Patent related litigations on Trastuzumab (Herceptin) were filed by Roche in India, as well. However, it’s good to note that on December 01, 2017, by a Press Release, USFDA announced the approval of Mylan’s biosimilar variety of Roche’s blockbuster breast cancer drug – Herceptin. Mylan’s Ogivri was co-developed with Biocon in India to treat breast or stomach cancer, and is the first biosimilar approved in the United States for these indications. It is noteworthy that Ogivri also has not been approved as an interchangeable product.

The global and local scenario for biosimilars:

Be that as it may, the July 26, 2017 study of Netscribes – a global market intelligence and content management firm estimates that the global biosimilar market will be worth USD 36 billion by 2022. Some of the major findings of this study are as follows:

  • With a cumulative share of nearly 85%, North America, Europe, and Japan are the major contributors to global biological and biosimilar sales. Asia and Africa account for 13.2% and 1.2%, respectively.
  • Pfizer is the leading player in the biologic market, with sales of nearly USD 45.9 billion in 2016 followed by Novartis (41.6 billion) and Roche (39.6 billion).
  • Biosimilar approvals are estimated to be around of around 16 to 20 biosimilars between 2018 to 2021 in both US and EU.
  • The US is not a favorable market for biosimilars due to a number of reasons, such as poor access to biologic drugs and an unfavorable regulatory environment.
  • South Africa is one of the best-suited markets for biosimilars due to a favorable regulatory environment and prescriber acceptance.

According to the April 2017 analysis of Research And Markets, biosimilars have started winning key government tenders in countries like Mexico and Russia, and being purchased by a growing number of patients in self-pay markets such as India. The aggregate sales of ‘copy biologics’ in the six BRIC-MS (Brazil, Russia, India, China, Mexico, and South Korea) countries would now almost certainly exceed USD 1.5 billion. Yet Another estimate  expects the Indian biosimilar market to increase from USD 186 million in 2016 to USD 1.1 billion in 2020. It is up to individual experts to assess whether or not this growth trend for biosimilars is desirable to adequately benefit a large number of patients, the world over.

Conclusion:

In my view, if what usually happens to sales and profit for small molecule blockbuster drugs post patent expiry, would have happened to the large molecule biologic drugs, the market scenario for biosimilars would have been quite different. In that scenario, one would have witnessed a plethora of biosimilar competition against high priced and money churning biologics, such as Humira, being launched with a significantly lesser price than the original brand.

Prices of biosimilars would have been much lesser primarily because, the litigation cost, now built into the biosimilar prices for successfully coming out of the labyrinth of patents after the basic patent expiry, would have been minimal. Moreover, restrictions on drug ‘interchangeability’ would not have made the target market smaller, especially in the United states.

Alongside, compliance with the regulatory need to meet the ‘interchangeability’ condition in the US, would drive the product cost even higher. More so, when this specific regulatory requirement is not necessary in other developed markets, like Europe. Both these factors would adversely impact affordability and access to sophisticated biologic drugs for patients, even after the fixed period of market exclusivity.

That said, a virtually impregnable patent labyrinth mostly ensures that going off-patent isn’t end of the road for blockbuster biologic drugs to continue generating significant revenue and  profit, any longer – and it would remain so at least, in the short to medium term.

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.