Tag Archives: biosimilar

Ticking Some Right Boxes Biosimilar Drugs’ Acceptance Gaining Steam in India

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Looking at a broader canvas, on September 19, 2023, a credible international report flashed a headline, ‘Biosimilars making inroads into Humira sales, but docs still cautious on switching: Spherix.’ This is based on a survey of U.S. healthcare specialists, including 80 dermatologists, 83 gastroenterologists and 81 rheumatologists.

This is indeed a significant development in the realm of biologic and biosimilar drugs, internationally. If this trend gathers a strong wind on its sales, it will effectively address the need for affordable biologic drugs, especially in life threatening ailments.

According to another January 05, 2023 report, Humira, which dominated the top of the global pharmaceutical brand ranking charts between 2012 and 2022, has slipped in 2023 to no 3 in ranking as it lost its last patent protection in the US in May 2022. Doctors’ gradual acceptance of biosimilars and the price could be a key differentiator among the competitors, potentially hastening Humira’s sales decline.

On July 31, 2017, I wrote an article in this blog captioned “Improving Patient Access To Biosimilar Drugs: Two Key Barriers.” Interestingly, 6 years down the line, reflecting the same sentiment – the above September 19, 2023, report also noted that ‘efficacy remains “top of mind” as prescribers’ leading concern for adalimumab (Humira) biosimilars, followed by safety concerns and an overall lack of cost savings.’

In today’s article, I shall particularly focus on the latest developments in India and the initiatives taken by the concerned stakeholders in this area. Let me start with a quick recap of biosimilar drugs, in my understanding, so that we all are on the same page while discussing the subject.

A quick recap: 

As we know, biologic drugs are medicines made from living organisms, such as bacteria, yeast, or cells. They are used to treat a wide range of conditions, including cancer, autoimmune diseases, and infectious diseases. Biosimilar drugs are highly similar copies of original biologic drugs that have gone off patent and are typically less expensive than the original biologic drugs. However, there are still some existing barriers to doctors’ fast and wider acceptance of biosimilar drugs by many.

Current global barriers to doctors’ fast acceptance of biosimilar drugs:

  • Lack of awareness and education: Many doctors are not familiar with biosimilar drugs or the regulatory process that oversees them. This lack of awareness may lead to skepticism and hesitation about prescribing biosimilar drugs to patients.
  • Concerns about safety and efficacy: Some doctors are concerned that biosimilar drugs may not be as safe or effective as biologic drugs. These concerns are often based on a misunderstanding of the regulatory process for biosimilar drugs. 
  • Financial incentives: Some doctors may be reluctant to prescribe biosimilar drugs because they receive financial incentives from biologic drug manufacturers. These incentives can take the form of speaking fees, consulting fees, and research grants. 
  • Regulatory uncertainty: In some countries, the regulatory framework for biosimilar drugs is still evolving. This uncertainty can make it difficult for doctors to know which biosimilar drugs are safe and effective, and how to use them effectively. 

Some contemporary examples show that these barriers still exist:

As shown by the following contemporary data available to the public:

  • In 2022, a study published in the journal JAMA found that only 25% of US doctors were aware that biosimilar drugs are just as safe and effective as biologic drugs.
  • In 2023, a study published in the journal Annals of Rheumatic Diseases found that only 30% of rheumatologists in the UK were willing to prescribe biosimilar drugs to their patients. 
  • In 2023, a study published in the journal Cancer found that oncologists in the US were more likely to prescribe biologic drugs to their patients if they had received financial incentives from biologic drug manufacturers. 
  • In 2023, a report published by the European Commission found that the regulatory framework for biosimilar drugs in the EU is still complex and fragmented.

Measures being taken to address these barriers, globally?

There are a number of things that can be done to address the barriers to doctors’ fast acceptance of biosimilar drugs. These include:

  • Education and outreach: More needs to be done to educate doctors about biosimilar drugs and the regulatory process that oversees them. This education should come from a variety of sources, including medical schools, professional organizations, and pharmaceutical companies.
  • Financial transparency: Pharmaceutical companies should be required to disclose all financial payments they make to doctors. This transparency will help to reduce the potential for conflicts of interest.
  • Regulatory harmonization: The EU should work to harmonize the regulatory framework for biosimilar drugs across member states. This will make it easier for doctors to prescribe biosimilar drugs to their patients.

By addressing these barriers, it is possible to increase the acceptance of biosimilar drugs and make them more accessible to patients. This will lead to lower healthcare costs and improved patient outcomes.

Indian scenario of biosimilar drugs, issues and actions:

As reported, India is a global leader in the production and development of biosimilar drugs. The Indian biosimilar market is expected to reach $30 billion by 2025. Biosimilar drugs in India are typically 30-70% cheaper than original biologic drugs. For example, a vial of the biologic drug Herceptin costs around INR 1 lakh, while a vial of the biosimilar drug Trastuzumab costs around INR 30,000.

The key reasons for price arbitrage:

The price difference between biosimilar drugs and original biologic drugs is due to a number of factors, including:

  • Lower development costs: Biosimilar drugs are less expensive to develop than original biologic drugs because they do not require the same level of research and clinical trials. 
  • Increased competition: There is more competition among biosimilar manufacturers, which drives down prices. 
  • Government support: The Indian government provides financial incentives to biosimilar manufacturers, which also helps to keep prices low. 

Biologic drugs, especially biosimilar insulin, some medications for cancer and a variety of autoimmune diseases, have been proved to be very effective for patients. That said, original biologic drugs can also be very expensive. Biosimilar drugs are making these drugs more affordable for patients.

Indian stakeholder initiatives and support is essential:

Indian key stakeholders are also supportive of the biosimilar industry and have taken a number of steps to promote its growth. Some of the recent ones are: 

  • In 2022, the Indian government announced a new policy that will give preference to biosimilar drugs in government procurement. This policy is expected to save the government billions of dollars in healthcare costs.
  • In 2023, the Indian government launched a new awareness campaign to promote the use of biosimilar drugs. The campaign is targeting doctors, patients, and healthcare policymakers.
  • In 2023, a number of leading private hospitals in India announced that they would be switching to biosimilar drugs for a range of conditions. These hospitals include Apollo Hospitals, Fortis Healthcare, and Max Healthcare.
  • In 2023, the Indian Pharmaceutical Alliance (IPA) released a report that found that the use of biosimilar drugs in India had increased by 20% in the past year. The report also found that the use of biosimilar drugs was expected to continue to grow in the coming years.

These are just a few examples of the growing acceptance of biosimilar drugs in India. As more and more doctors and patients become aware of the benefits of biosimilar drugs, we can expect to see their use continue to grow in the coming years.

State-specific advantages for greater acceptance of biosimilar drugs in India: 

As available from different reports, the following are some specific examples of state-specific advantages that have led to the greater acceptance of biosimilar drugs in India:

  • In 2022, the government of Maharashtra launched a scheme to provide financial incentives to doctors who prescribe biosimilar drugs. Under the scheme, doctors who prescribe biosimilar drugs to at least 20% of their patients are eligible to receive a bonus of up to INR 10,000 per month.
  • In 2023, the government of Gujarat launched a campaign called “Biosimilar Drugs: Safe, Effective, and Affordable.” The campaign aims to educate doctors and patients about the benefits of biosimilar drugs and to dispel any myths or misconceptions about them. 
  • The states of Karnataka and Telangana have a number of leading biopharmaceutical companies that are developing and manufacturing biosimilar drugs. These companies are working with doctors and hospitals in these states to promote the use of biosimilar drugs. 

As a result of these advantages, the acceptance of biosimilar drugs is growing rapidly in some states in India. For example, in Maharashtra, the use of biosimilar drugs increased by 25% in the past year.

Conclusion:

Against the above backdrop, I reckon, the acceptance of biosimilar drugs is gaining steam in India now. This is due to a number of factors, including rising costs of original biologic drugs, government support, growing availability of biosimilar drugs, and increasing awareness and education.

It is important to note that biosimilar drugs are just as safe and effective as original biologic drugs, but they are much more affordable. This is making it possible for more patients to access the treatment they need, especially for life-threatening ailments. 

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.

 

Big Pharma Fails Avoiding Drug Price ‘Control’? Even In The US? Why?

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It ultimately happened – even in the United States, as the US President signed a bill on August 16, 2022 that aims to reduce healthcare costs, alongside fighting climate change, besides raising taxes on the rich. This new law was enacted, despite powerful lobbying and the vehement opposition of big pharma associations and that too in their home turf.

According to the Fierce Pharma report of the same day, since the current US President moved into the White House in 2020, the drug industry left no stone unturned battling to preserve pricing status-quo. It further added, the ‘pharmaceutical industry, including, PhRMA, its allies, and the nation’s largest pharmaceutical firms’ have spent more than $205 million in multi-media ads opposing ‘Medicare price negotiations’ and lobbying against efforts to lower drug prices for consumers.’

No wonder, when the bill was just introduced to the US lawmakers, big pharma’s disappointment on the bill was palpable. This gets well-captured in what the AbbVie CEO pointed out at that time. He said, ‘the legislation would force manufacturers to accept the government’s proposed price or face a harsh tax on their revenues from a given product.’ He also said: “So, it’s not a negotiation,” as stated in the bill. He further opined in his conference call: “We should just call it what it is. It’s price controls,’ which is what the lawmakers are ‘basically putting in place, if the language stays the same,’ the AbbVie chief added.

Capturing this new development in the United States, at least, in the recent past - Fierce Pharma in its August 08, 2022, issue commented: “The seemingly unstoppable pharma lobbying force has lost its charm. With the passage of a new bill, the U.S. Senate is opening the door to major drug pricing reform, leaving the drug industry licking its wounds.”

In the Eldorado of the global drug industry, this is indeed an unprecedented initiative to significantly reduce costs of many important drugs and reduce patients’ out of pocket expenses. Consequently, it has created so much of hullabaloo, across the world, for various reasons. In this article, I shall track this emerging scenario along with the message that it sends across the globe, and its possible impact on new drug innovation to meet unmet needs of patients. In India, one such area could be revisiting the price negotiation proposal for patented drugs, a government initiative that failed to take off earlier.

Would lowering prices stifle new drug innovation?

The apprehension, I reckon, that big pharma will continue to play with - price control will stifle new product innovation – adversely impacting patient interest. Notably, to many industry experts, this argument doesn’t just lack robustness, seems more a conjecture rather than the outcome of any peer- reviewed research study findings. On ewthe contrary, several highly credible and independent studies prove otherwise. Thus, let me put hereunder:

  • One – what big pharma directly and through their powerful industry associations or some financially sponsored studies are saying
  • And – what the top experts concluded from their independent analysis in this regard, as published in the globally acclaimed journals.

I leave it to my readers to evaluate the credibility of each to form their views.

Drug industry arguments supported by recent studies:

The findings of a study conducted recently, with the financial support of the Pharmaceutical Research and Manufacturers of America (PhRMA), the Biotechnology Innovation Organization (BIO), Amgen, Pfizer, Alexion, AbbVie, Genentech, and Bristol Myers Squibb, were released by PhRMA on November 23, 2021. The study was conducted by Vital Transformation. The key findings of this study highlighted: ‘Every 10% drop in the price of medicines in price-controlled EU markets was associated with a:

  • 14% decrease in total VC funding (10% early stage and 17% late stage)
  • 7% decrease in biotech patents
  • 9% decrease in biotech start-up funding relative to the US
  • An 8% increase in the delay of access to medicines.

It concluded: ‘Drug pricing controls implemented in the US would likely have an even greater impact on Biopharma KPIs given its global leadership in investment and innovation.’

Independent expert studies, published in highly reputed journals:

Around the same time as the above report, an independent study published in the Harvard Business Review (HBR) on October 01, 2021, found exactly the opposite. It categorically stated: ‘The U.S. can lower drug prices without sacrificing innovation.’

The paper summed up: ‘With Congress considering legislation to allow Medicare to use its bargaining power to negotiate lower drug prices, large pharmaceutical companies are once again waging a campaign that contends that doing so would seriously harm the development of breakthrough drugs. This is not true. Smaller companies now account for the lion’s share of such breakthroughs. The key to supporting drug innovation is to increase NIH funding of the efforts that give rise to these new companies, cut the costs, and accelerate the speed of clinical trials, and reform patent law.’

Drug pricing in the Indian context:

Prices of, especially, new drugs and the overall cost of healthcare are two major concerns – more in the developing countries like India. Responding to this need drug price control for pre-defined essential medicines are already in place in the country. More recent studies further vindicate the relevance of such regulation from the perspective of affordability of drugs for the poorer section of the society, and where out of pocket expenses are very high.

Let me quote one such paper, published on June 04, 2022, which received no outside financial support from this study, where the researchers concluded: ‘With induced demand and an inadequate competitive environment, the pharmaceutical industry fails to reduce prices. Supply-chain trade margins are very high. Hence, government intervention through price control of essential and life-saving drugs is a necessity in India.’

In this context, another question that is being raised – are there other alternatives to expand access to high-priced life-saving drugs at an affordable cost to all those who need those most? The most common alternative that floats, encourage more competition for those drugs as soon as they go off patent. Let me examine what’s big pharma players are doing in that area.

Does Big Pharma encourage increasing competition to reduce drug prices?

Another way to reduce the price of an expensive product is encouraging competition to enable market forces bring down the price. An interesting article on breaking the rule of drug pricing by pharma companies was published in the Forbes magazine on June 29, 2022. I also wrote on June 10, 2013: ‘To scale-up access to health care, especially for the marginalized population of any country, greater access to affordable generic drugs will always remain fundamental, besides improving healthcare infrastructure and its delivery mechanism.’

Thus, there should be a robust mechanism, across the world, to facilitate quick entry of cheaper generic equivalents immediately after patent expiry of the original molecule. Increasing attempts of blocking entry of generics surreptitiously by vested interests, leaves no other alternative, but price control. This is imperative, ‘as without the availability of newer generics, unmet medical needs of the most vulnerable section of the society cannot be met effectively by any country, as I wrote there.

Attempts to game the system to minimize competition continue unabated:

Even after my article, this red flag is being raised for quite some time. It will be evident from another Harvard Business Review article titled, ‘How Pharma Companies Game the System to Keep Drugs Expensive,’ published in the on April 06, 2017. Acknowledging: ‘Drug development is risky and expensive, thanks to the long testing and approval process,’ the author concluded from their study – ‘But, increasingly, makers of branded drugs are using a variety of tactics to extend their exclusive rights,’ enabling them to maintain high drug prices for much longer time.

More recently, the above Forbes article of June 10, 2022 also highlighted, ‘even the most generous patent protections come to an end and companies must face the potential for generic competition. That’s when major drug manufacturers shift tactics from influencing policy to crushing the competition.’ There are several legal and semi-legal approaches that big pharma players adapt to game the system and maintain pricing monopoly. Let’s recap it with just three of these examples:

- ‘Patent Thicket: Delaying entry of lower price off-patent molecule through a Patent Thicket. This involves creation of ‘a dense web of overlapping intellectual property rights that a generic pharma company must hack its way through in order to actually commercialize new technology of a drug molecule,’ even after the original patent expires. For example, AbbVie’s Humira, the world’s best-selling drug for a long time. I also discussed this issue in my blog over three years ago – on April 22, 2019.

- ‘Pay-for-delay deals’:  I discussed this issue in this blog on June 19, 2013. Moreover, the above Forbes article of June 29, 2022, also underscored this tactic. It explained that this is a deal in which drug companies agree not to compete for a set amount of time to maintain high prices of their brand-name drugs. The article, published in Bloomberg Law on February 20, 2020, captures it nicely.

- Authorized generics: As many would know, law permits six months of exclusivity to the first generic version of an off-patent new molecule coming into the market. Interestingly, just before patent expiry of an innovative drug, several drug makers roll out their own generics to stifle competition. Although, they keep different names for the generic versions, but pricing remains almost similar. Such a practice obliviously delays the entry of cheaper generics, at least by six months.

In this scenario, the new drug prices continue racing north. Something was to be surely done – for patients’ sake, as many believe, at least, where it all started – the US.

New drug prices are highest in 2022:

As reported by Reuters on August 16, 2022:

  • Eight of 13 drugs launched in 2022 priced over $200,000 per year
  • Median annual price for new U.S. drugs this year is $257,000
  • Some drugmakers disclose less information on pricing

Despite this, as reported on August 15, 2022: ‘The main U.S. drug lobby has said it will push back against the legislation, which includes policies that drug makers have opposed for decades.’

Conclusion:

The significance of the above development in the US healthcare scenario, was aptly summed-up by the US House Speaker, as she said: “If you are sitting at your kitchen table and wonder how you’re going to pay the bills – your health care bills, your prescription drug bills – this bill is for you.” For the first time in the US – the champion of champions of free-drug pricing market, will negotiate the drug price with their manufacturers to become patient -centric.

The reverberations of this difficult decision, especially on new drug prices, are expected to prompt the need for price negotiation or price control, primarily for expanding access to new drugs for a larger number of patients. This deserves to be a focus area for the Government, including India. Moreover, the August 18, 2022, media report also suggests that the top court of India may now encourage the Government to investigate, report and take remedial action on drug industry malpractices.

Finally, it’s worth noting that over a decade ago, international media widely reported -  ‘India considering price controls for patented drugs.’ Its objective was to address the aggressive new drug pricing trend in the country. Accordingly, the price negotiation proposal for patented drugs was notified by the Department of Pharmaceuticals (DoP) in 2007. The constituted Committee submitted a report, as well, on February 21, 2013. But it did not take off as on date. Many apprehend, this is due to intensive and ongoing lobbying by big pharma, just as what happened in the US. Nevertheless, the question that surfaces – will the above new drug law in the largest pharma market in the world encourage the DoP to revisit price negotiation for patented drugs - to make modern drugs affordable to a larger patient population in India – now?

By: Tapan J. Ray

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

A Game-Changing Non-Covid Drug Approval In the Pandemic Milieu

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Amid high decibel deliberations on Covid-19 pandemic, something similar to groundbreaking happened – involving Biosimilar drugs, in just a couple of months ago. On July 28, 2021, in the Eldorado of the pharma industry, the US-FDA approved  the first ‘interchangeable’ biosimilar drug, for wider access to modern and much affordable treatment of diabetes. This is expected to open new vistas of opportunity for biosimilar drugs, in general, across the world.

The development is even more interesting, as the product named Semglee belongs to India’s largest biopharmaceutical company - Biocon Biologic. It’s an ‘interchangeable’ biosimilar insulin glargine, referencing Sanofi’s, reportedly  the second best-selling product in 2020 - Lantus. Notably, the Biocon product was launched in 2020 without the ‘interchangeability’ designation.

Although, the patent of this long-acting insulin (glargine) – used to treat diabetes type I and II, expired during 2015, in 2020 also Lantus generated some 2.7 billion U.S. dollars worldwide. Many envisage, the approval of this first ‘interchangeable’ biosimilar insulin glargine will foster stronger competition in the insulin market, which is currently dominated by a handful of brands, like Lantus – and characterized by their stubbornly high prices.

In today’s article, I shall focus on what it means to pharma marketers for greater market access to ‘interchangeable’ biosimilar drugs.

What ‘interchangeability’ really means:

As I wrote in my article on July 31,2017, there are two key barriers to improving patient access to biosimilar drugs, and one of which is the issue of their ‘interchangeability’ with original biologic drugs. It means, besides being highly similar, a biosimilar drug would require indisputable clinical evidence – that it gives the same result to patients, just as the original biologic medicine.

Thus, lack of the ‘interchangeability’ designation makes many physicians hesitant to switch, for all those existing patients who are on expensive original biologic drugs, to less expensive available biosimilar alternatives. Only new patients in that case, are prescribed biosimilar drugs, sans ‘interchangeability’ label from the drug regulator, especially in the US.

Overcoming a tough barrier to biosimilar market growth:

This was echoed by another article on ‘Interchangeability’ of biosimilars, published in the Pharmaceutical Journal on July 22, 2020. It wrote, ‘One of the hurdles in the adoption of biosimilars is the lack of interchangeability with reference biologics.’ While interchangeability is an important issue for doctors, ‘different definitions and regulatory frameworks that exist in the United States, Europe and other jurisdictions add to the complexity.’

What the ‘interchangeable’ designation of Semglee will really mean, in terms of affordability to patients, was lucidly explained in an article, published in the AJMC – the center for Biosimilars – on July 29, 2021. It underscored: ‘An interchangeable designation means that Semglee can be substituted for Lantus automatically by pharmacists without physicians’ permission.’ As reported, Semglee will cost nearly 3 times less than the list price of Sanofi’s Lantus, which in 2019 clocked in at $283.56 for a single vial and $425.31 for a box of five pens, in the US.

Are interchangeable biosimilars superior to other biosimilars?

The ‘interchangeable’ designation is not meant to suggest that such biosimilars are superior to ones without this label. However, to obtain the ‘interchangeable’ designation, biosimilar manufacturers are required to perform ‘switching studies.’ These provide evidence that patients who are using originator’s biologic drug, when switch to a comparable biosimilar, do not experience higher rates of adverse events or decreased efficacy. The same has also been clearly explained in the AJMC article of July 29, 2021, as mentioned above.

But, if marketed well, ‘interchangeable’ biosimilars can provide a cutting edge to encourage consumers to switch to the less-expensive ‘interchangeable’ versions of the original higher priced biologic drugs. Consequently, more economical ‘interchangeable’ biosimilars would carve out a larger market share, creating a win-win situation. For patients, it will expand affordable access to biologic drugs- and for the company increased revenue from the expanding biosimilar market, as several studies point out.

Expanding biosimilar market:

According to the IQVIA report of March 04, 2021, the global biosimilars market currently shows double-digit growth and is expected to maintain a similar level of uptake in the coming years. This will be driven by the rising incidence of chronic diseases and the cost-effectiveness of biosimilars, especially as more stringent cost-containment measures are likely – post COVID-19 pandemic.

The paper concluded, biosimilars will continue to register impressive growth in their market share, aided by patent expiries and regulatory improvements which will permit easier and more rapid market access. Many pharmaceutical companies – having witnessed this trend, are now preparing to leverage the biosimilar opportunity. However, marketing large molecule biosimilar drugs will not be quite the same as marketing small molecule generics. 

Estimated savings to patients with biosimilars – in Covid-19 context:

As the IQVIA Institute estimates, over the next five years biosimilars could globally contribute a cumulative $285 billions of savings to patients and payers. To put this in context, it says, over the same period, around $150 billion will be spent on COVID-19 vaccines. According to a senior IQVIA official, as quoted by Reuters Events of July 2, 2021: “The five-year savings from biosimilars could almost double the amount of incremental spending that will be going out to get everybody vaccinated around the world.”

Going by the IQVIA data, biosimilars are between 20% and 50% more affordable. And this is especially at a time when affordability drives a lot of healthcare - sustainability that has emerged as a major issue during the pandemic.

Conclusion:

Currently, in many countries of the world, alongside Covid vaccination drive in top gear, creation of a disruptive pandemic-specific – a robust health infrastructure for the future, is yet to be in place. More importantly, public health facilities, especially in India, are still struggling hard to meet affordable health care needs of patients – sans restrictions or apprehensions of getting infected by Covid-19.

Against this backdrop, the very first approval of an ‘interchangeable’ biosimilar drug, in the Eldorado of pharma business – the US, brings a new hope to many patients, in 2021. An expectation of reducing their healthcare burden, significantly. This will happen, as the prescribers muster enough confidence to advise patients switching from highly expensive original biologic to more affordable ‘interchangeable’ biosimilar drugs, as and when these are launched.

In tandem, with this growing new confidence, others – even ‘non-interchangeable’ biosimilar drugs, will be able to deliver more value being, besides greater affordability – wider access to sustainable-treatments for patients.

This comes, possibly with a caveat. Biosimilar drug marketers will need to chart a new marketing frontier, without holding on to their pre-covid strategies – especially for large molecule biosimilar drugs.

From this perspective, the US-FDA’s regulatory approval of the first ‘interchangeable’ biosimilar insulin to Sanofi’s high-priced Lantus, carries a game-changing potential in the biosimilar drug market, for astute pharma marketers to leverage.

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.

Spirit Behind Drug Patent Grant: Secondary Patents: Impact on Drug Access

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For more effective treatment against existing diseases, besides combating new or a more complicated form of existing ailments with precision, drug innovation is absolutely necessary and on an ongoing basis. This makes innovative drugs so important for the population, globally.

Besides academia, the pharma industry has remained in the forefront of the search for new drugs, for so long. What makes this process so crucial is, cheaper generic drugs flow from the innovative drugs, post market exclusivity period, which together form the bedrock of the pharma industry’s business model. Consequently, a robust patent protection for the new molecular entities, not only enable the drug innovators to make a reasonably good profit, but also encourage them to keep this virtuous circle moving, faster.

Although, the drug patents are granted for 20 years, after obtaining marketing approval from the respective drug regulators, a time period - ranging between 7 and 12 years, is available to the company to realize its maximum commercial benefits. Thereafter, the patent expires, paving the way of market entry of cheaper generic equivalents to make the drug accessible to a larger population. This is the playbook, which deserves to be accepted and respected by all, both in the letter and spirit.

Currently, the narrative has started changing, apparently, repudiating the spirit behind the grant of new drug patents, especially with the entry of a number of expensive, large molecule biopharmaceutical drugs. After obtaining a fixed-term market exclusivity, more intricate legal measures are being taken to extend the fixed-term market monopoly for an unknown period, delaying market entry of cheaper biosimilar equivalents, post patent expiry, as long as possible.

In this milieu, India appears to be the only country in the world, where the country’s ‘Patents Act’ provides enough safeguard to blunt those legal tools, effectively, to protect patients’ health interest. Quite expectedly, this new narrative of the drug innovators is yielding the best return in the Eldorado of the pharma world – the Unites States. It is also no secret that US vehemently opposes several provisions of the Indian Patents Act 2005, under pressure from the most powerful pharma lobby group, as many believe.

Using the spirit behind drug patent protection as the backdrop, I shall dwell in this article, how this so precious spirit is gradually losing its basic purpose, especially for blockbuster biopharma drugs. Is the key intent behind sacrificing the spirit behind drug patent grant to keep their brands money spinners and big – even after expiry of original patent – as long as possible – at the cost of patients’ health interest?

Despite the original patent expiry, biggest biologic drugs remain big:

The fact that original patent expiries have done little to halt sales of some of the industry’s biggest products – mostly biologic drugs, was clearly elucidated in an  Evaluate Pharma article – “Biopharma’s biggest sellers – the oldies that just keep giving,” published on August 14, 2019. This gets vindicated, as we look at the ‘top ten pharma brands with biggest lifetime sales – from launch to 2018’, in the following Table I:

Product Company Launch year USD Billion
1. Lipitor Pfizer 1997 164.43
2 Humira AbbVie 2003 136.55
3. Rituxan Genentech/Biogen 1997 111.50
4. Enbrel Amgen 1998 108.16
5. Epogen Amgen 1988 107.90
6. Advair GSK 1998 104.20
7. Remicade Janssen 1998   98.00
8. Zantac GSK 1981   97.42
9. Plavix Sanofi/BMS 1998   90.63
10. Herceptin Genentech/Roche 1998   87.97

(Adapted from Evaluate Pharma data of August 14, 2019)

The point to take note of:

The point worth noting here, with the exception of Advair, Zantac, Lipitor and Plavix, all others – among the top ten brands, are biologic drugs. Moreover, what is most striking in the Table I, despite the expiry of the original patents, a large number of biologic brands were able to expand their sales, pretty impressively, for well over two decades. As we shall see later, this situation is expected to continue, at least, till 2024.  As the Evaluate Pharma article states, for various reasons, these multibillion dollar brands have been able to avoid the expected post patent expiry ‘onslaught from biosimilars in the key US market’, which is incidentally the most valuable pharma market in the world.

One of the key reasons that helps delaying cheaper biosimilar drug entry expanding patient access, is a crafty strategic measure adopted by these companies through the creation of a Patent Thicket with secondary patents. As I discussed in this Blog on April 22, 2019, this is a crafty way of ‘evergreening’ patent term beyond 20 years, legally. Whether such measures conform to the spirit of granting 20 years product patent, becomes a moral question, or an issue of probity for the concerned companies, at the most. Be that as it may, a concern over this situation has been raised in many countries, including the United States.

Barrier of secondary patents: 

Biosimilar drug developers continue facing multiple non-financial challenges, such as, scientific, regulatory, pricing. I have already discussed some of these barriers in this blog on July 31, 2017. Instead, I shall focus in this article, with greater detail, on the intricate and a well-woven net of secondary patents. However,before delving into this area, it will be worthwhile to have a quick recap on the basic differences between original patents and secondary patents.

According to WIPO, “Patents on active ingredients are referred to as primary patents. In later phases of the drug development, patents are filed on other aspects of active ingredients such as different dosage forms, formulations, production methods etc. These types of patents are referred to as secondary patents.”

Another excellent paper, authored by two distinguished researchers from Columbia University and LSE, makes some important points on this subject. It says, secondary patents have become increasingly important to the pharma industry, especially in the U.S. and Europe over the past three decades. The basic purpose of ‘taking out multiple patents on different aspects of a drug in order to cordon off competitors is now standard practice in the pharmaceutical industry.’ As the authors further said, this is primarily because: ‘Secondary patents can protect market shares by extending periods of exclusivity beyond the dates in which patent protection would otherwise lapse.’

Interestingly. devising patent strategies to extend periods of market exclusivity is generally considered in the industry, as a key component of ‘product life cycle management,’ – not by the marketing whiz kids, but by astute patent attorneys. Nevertheless, as the paper articulates, critics of this practice often use the more pejorative – evergreening, to describe it.

Examples of impact of secondary patents:

Many research papers suggest, besides scientific complexity in biosimilar drug development being a key reason for their delayed market entry, secondary patents are even tougher barriers for the same. This was brought to light a few years ago in a ‘Review Article’ – ‘The Economics of Biosimilars’, published in the September/October 2013 issue of American Health & Drug Benefits.

Some of the key points made on this issue include,AbbVie plan to defend Humira (adalimumab) with more than 200 secondary patents, Merck’s giving up its biosimilar project on Enbrel when Amgen got its expanded patent life. There are many other such instances.

Its effect would last longer: 

Experts believe, the effect of creating a strong secondary patent shield around blockbuster biologic would last much longer. As the above Evaluate Pharma article underscores: ‘This ability to fend off biosimilar competition is one of the reasons Humira is set to snatch Lipitor’s crown next year as the industry’s most successful drug.’

The Table II below that lists ‘top 10 pharma brands from their respective launch date, including estimated forecast till 2024’, vindicates its long-lasting impact:

Product Company Launch year USD Billion
1. Humira AbbVie 2003 240.05
2 Lipitor Pfizer 1997 180.19
3. Enbrel Amgen 1998 139.83
4. Rituxan Genentech/Biogen 1997 136.07
5. Revlimid Celgene 2008 123.64
6. Remicade Janssen 1998 117.20
7. Epogen Amgen 1988 115.87
8. Herceptin Genentech/Roche 1998 114.89
9. Avastin Genentech/Roche 2004 114.27
10. Advair GSK 1998 113.61

(Adapted from Evaluate Pharma data of August 14, 2019)

Although, Zantac and Plavix no longer feature in this table, one drug that leapfrogged much of the competition to become one of the industry’s biggest future bestsellers is Revlimid. The projected sales of the drug over the next six years will actually outstrip its sales to date. However, much of this is dependent on whether generic competition will arrive ahead of Revlimid’s 2022 patent expiry, the paper indicated.

Concern expressed even in the US for the delay in biosimilar market entry:

Many big spending countries on health care, such as the United States expected that timely biosimilar drug entry will help contain health expenditure significantly. However, the article published in the Fierce Pharma on August 29, 2019, raises an alarm, but with a hope for the future. It says: “It’s no secret biosimilars haven’t made a big dent in U.S. drug spending. Some experts have even said it’s time to give up on copycat biologic.”

This hope gets resonated with what, ‘the former US-FDA commissioner Scott Gottlieb argues’. He feels, ‘It’s too soon for that’, while ‘calling on Congress to bolster the budding market.’ However, in my personal view, this will remain a difficult proposition to implement, as biologic drug players will continue using their relatively new, but powerful weapon of filing a number of complex ‘secondary patents.’ These will help extend the market exclusivity period of their respective brands, much beyond the original patent grant period, unless a counter legal measures are taken by the lawmakers of various countries, including the United States. But, India is an exception in this regard.

Indian patent law doesn’t encourage ‘secondary patents’:

The good news is, Indian Patent Act 2005, doesn’t encourage ‘secondary patent.’ This is because, section 3 (d) of the Indian Patent Act 2005 limits grant of ‘secondary pharmaceutical patents.’ An interesting study reported on February 08, 2018, discussed about 1,700 rejections for pharma patents at the IPO spanning over the last decade. But, there is a huge scope for improvement in this area.

Which is why, the not so good news is under-utilization of the same section 3.d by the Indian Patent Office (IPO), as are being voiced in many reports. One such paper of April 25, 2018 highlighted,72 per cent of pharma patent grants are secondary patents. These were granted for marginal improvements over previously known drugs for which primary patents exist. That said, despite such reported lapses, blocking of some crucial secondary patent grant has benefited a large number of patient population of India.

Blocking secondary patent grant has helped India immensely:

While US recognizes secondary patents, blocking secondary patent grant, especially for biologic drugs has helped Indian patients immensely, with expanded access to those medicines. This was also captured in the above study. Besides the classic case of Novartis losing its secondary patent challenge for Glivec in the Supreme Court of India in 2013, several other examples of secondary patent rejection are also available. This includes, among others, Glivec of Novartis and the world’s top selling drug for several years – Humira of AbbVie.Against a month’s therapy cost of ₹1,6o, ooo for Glivec in the US, its Indian biosimilar version costs for the same period ₹11,100. Similarly, while the treatment cost with Humira in the US is ₹85,000, the same with its biosimilar version in India is ₹ 13,500, as the above study finds.

Conclusion:

The core purpose of drug innovation, as widely touted by the R&D-based drug companies, is meeting the unmet needs of patients in the battles against diseases. Thus, drug innovation of this genre must not just be encouraged, but also be adequately protected and rewarded by granting product monopoly for a 20-year period from the date of the original patent grant. Curiously, piggybacking on this basic spirit behind the drug patent grant, pharma lobby groups are now vocal on their demand for giving similar treatment to secondary patents on various molecules. The tone of demand gets shriller when it comes to section 3. d of the Indian Patents Act, which doesn’t allow such ‘evergreening’ through secondary patents.

Thus, the key question that surfaces, while the original patent grant for innovative drugs help meeting unmet needs of some patients, whose unmet needs would a secondary patent grant meet, except making the concerned company richer? Further, for highly expensive biologic drugs, delayed market entry of cheaper biosimilars in that process, would deny their expanded access – failing to meet the unmet needs of scores of others.

Hopefully, India won’t give in to pressure of multinational pharma lobby groups, channeled through various powerful overseas government entities. At the same time, I hope, the government in power at the Eldorado of the pharma industry, will consider giving a fair chance of market entry to cheaper biosimilars, including those from India, to also grow their business globally, but in a win-win way.

The key objective of all stakeholders involved in this process, should be to uphold the basic spirit behind drug patent grant. It may even call for challenging the core intent behind secondary patent applications, the world over, that deny quicker market entry for cheaper biosimilars, sans heavy litigation expenses. This will help expand access to cheaper biologic medicines to all those who can’t afford those, otherwise.

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.

 

 

 

 

Will ‘Patent Thicket’ Delay Biosimilar Drug Entry in India?

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Do pharma and biotech investors encourage companies indulging in ‘patent thicket?’ This question recently grabbed media headlines. On April 02, 2019, one such report brought out: AbbVie investors are calling for the Chair-CEO power split, flagging the CEO’s USD 4 million bonus payout, fueled by the company’s Humira ‘patent thicket’ strategy related aggressive price hikes. It prolonged the brand’s market monopoly, blocking entries of its cheaper biosimilar equivalents.

I have discussed some related issues in this blog, previously. As the issue is gaining relevance also in the Indian context, this article will deliberate the ill-effects of ‘patent thicket’ on patient health-interest. The sole beneficiaries for the creation of this self-serving labyrinth are the manufacturers of high-priced patented drugs, as reported above. Before I proceed further, let me recapitulate what exactly is a ‘patent thicket.’

‘Patent Thicket’:

The dictionary definition of patent thicket is: ‘A group of patents in a field of technology which collectively impede a party from commercializing its own patents or products in that field.’In the current context, it means a dense web of overlapping patent rights that restrict a generic or a biosimilar drug maker from commercializing its cheaper equivalents post expiry of the original patent.

This scenario has been well-captured by the above media report, which states: “AbbVie leadership has also been accused of creating a ‘patent thicket’ in its battle to stave off biosimilar competitors to Humira.” Boehringer Ingelheim is among the few still fighting AbbVie’s ‘patent thicket’ hoping to launch its Humira biosimilar - Cyltezo, even after receiving US-FDA approval on August 29, 2017. ‘Top biosimilar makers, including Novartis’ Sandoz unit and Mylan, have settled their own Humira patent fights with deals that put off launches until 2023,’ the report indicated.

In its favor: AbbVie says, Cyltezo infringes about 70 patents the company currently holds for Humira. Whereas, ‘Boehringer’s lawyers say AbbVie’s copious patents overlapped in an attempt to exclude competitors from the market.’ Notably, in March this year, New York’s UFCW Local 1500 Welfare Fund, reportedly, also accused AbbVie of using overlapping patents to exclude biosimilars.

‘Patent thicket’ – a way of ‘evergreening’ beyond 20 years patent term:

Much concern is being raised about various ploys of especially by the drug MNC and their lobby groups – directly or under a façade, to delay entry of cheaper generic drugs for greater patient access. Mostly the following two ways are followed for patent ‘evergreening’ beyond the term of 20 years:

  • ‘Incremental innovation’ of the existing patented drugs through molecular manipulation, with its clinical performance and safety profile remaining similar to the original one. As the cost benefits of such drugs are not shared with patients, cannibalizing the sales of the older molecular version with the newer one highlighting its newness, the sales revenue can be protected. With this approach, coupled with marketing muscle power with deep-pocket the impact of generic entry of the older version can almost be made redundant. For example: Omeprazole was first marketed in 1989 by AstraZeneca, under the brand name Losec (later changed to Prilosec at the behest of the US-FDA). When Prilosec’s US patent expired in April 2001, AstraZeneca introduced esomeprazole (Nexium) as a patented replacement drug. Both are nearly identical in their clinical efficacy and safety.
  • ‘Patent thicket’ is yet another tool for ‘evergreening’, delaying launch of similar drugs, or resorting to ‘pay for delay’ sort of deals. As another recent report reiterates, AbbVie’s ‘patent thicket’ for Humira, has deterred other potential challengers, such as Amgen, Samsung Bioepis and most recently Mylan, each of which struck settlements with AbbVie to delay their biosimilar challenges in the United States.

Goes against patients’ health interest:

On May 09, 2018, the Biosimilars Council reported, just as generic medicines saved Americans USD 1.67 trillion in the last decade, biosimilars are poised to do the same – ‘if they aren’t thwarted by delaying tactics instituted by some pharmaceutical companies.’ Echoing similar concern, the outgoing US-FDA Commissioner Scott Gottlieb also, reportedly said, ‘some drugmakers are using unacceptable tactics such as litigation and rebate schemes to stall the entry of cheaper copies.’

‘Of the nine biosimilars the FDA has approved to date, only three have made it into the hands of patients – an alarmingly small number. Patients can’t access the six others due to barriers thrown in their way by pharmaceutical companies that want to protect their monopolies and keep prices high,’ highlights the Biosimilars Council report. Net sufferer of this self-serving ‘patent thicket’ strategy of pharma and biotech players to extend product patents beyond 20 years, are those patients who need these drugs the most – to save their lives.

Despite law, patent ‘evergreening’ still not uncommon in India:

With section (3d) on the Indian Patents Act 2005 in place, the country is expected to protect itself from patent ‘evergreening’ through ‘incremental innovation.’ This section articulates:“For the purposes of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy.”

On this ground, Indian Patent Office (IPO) rejected Novartis’ drug Glivec (imatinib mesylate) patent application, which was ultimately upheld by the Supreme Court in 2013. Nevertheless, a study report of April 30, 2018 emphasized: ‘Though the law with regard to anti-evergreening, upheld and clarified by Indian courts, remains on the books, its application by the IPO has been far from satisfactory.’

The esteemed author of the report, after analyzing about 2,300 drug patents, granted between 2009 and 2016 concluded that evergreening practices may be rampant in India. The report pointed out, ‘the IPO could be operating with an error rate as high as 72 percent for secondary patents, despite provisions to keep them in check.’

Are these IPO’s mistakes, or due to external pressure?

As the paper, published in the January 2016 edition of the Journal of Intellectual Property Rights (JIPR) said,‘The multi-national pharma companies (MNCs) and the US-India Business Council (USIBC) have suggested in their report for elimination of Section 3 (d) so that drug patents can be granted in India for incremental improvement and modification. As per US 301 report, India is listed among countries with inadequate IP regime.’ Keeping all these aspects into consideration, the article expressed some key concerns pertaining to the impact of Section 3 (d) with special emphasis on its interpretation. Does it mean any possibility of wilting under such extraneous and high impact pressure?

A fresh pressure from drug MNC on the DCGI:

Since long drug MNCs have been attempting to delay the entry of even those generics, which are fully compliant with the Indian Patent Law 2005. One such effort was their demand for ‘patent linkage’ with the marketing approval of new generic drugs. However, it could not pass through legal scrutiny – first by the Delhi High Court in the Bayer Cipla case in 2010, and then by the Supreme Court – on the same case. The Court, reportedly, ‘noted the Indian patent system was distinct from the drug regulatory system with no linkage between them and so Bayer can’t prevent DCGI from granting marketing approval to generic versions of patented drugs.’

According to another recent media report of April 04, 2019, in a fresh endeavor ‘to delay launch of low priced generic medicine, multinational drug makers have asked the government to create a registry providing information about all drug applications pending manufacturing and marketing approval. The proposal, which is still pending with the Department of Pharmaceuticals (DoP), if accepted, could involve the generic players into expensive and time-consuming litigations, delaying early market entry of the cheaper generic or biosimilar equivalents.

To date, the health ministry has opposed the proposal, as it will be “unfair to local drug manufacturers to disclose their product strategy” and also has “the potential to substantially increase health care costs for the public.” The government further argued, “such information about product applications filed for approval are not disclosed anywhere in the world.”

India encourages new drug innovation, but not at any cost:

Despite shrill and disparaging comments of MNC lobbyists and the strong vested interests, that India’s Patent Law 2005, doesn’t encourage innovation, many independent international experts do praise the same for the following reasons:

  • Does encourage new drug innovation
  • Does extend product exclusivity for twenty years
  • Strikes a right balance with patients’ health interest
  • Indian judicial system deals with patient infringements and disputes, just as any other developed countries
  • Even 14 years after the enactment of patent laws, just one compulsory license has been granted, which is much less than other countries, including the United States.

What India doesn’t legally allow is, unfettered profit making through ‘evergreening of drug patents’ – at the cost of millions of patients-lives. Nonetheless, powered by deep pockets, the pharma and biotech players are unlikely to cease from this practice, anytime soon. Only patient-awareness, and stringent counter-legal measures can contain this unfair game of drug monopoly practices – in the name of ‘encouraging innovation’.

Conclusion:

The article titled, ‘Over patented, overpriced: How Excessive Pharmaceutical Patenting is Extending Monopolies and Driving up Drug Prices’ revealed:“Top grossing drugs have on average 125 patent applications, which are filed with a strategic intent to extend the commercial monopolies far beyond the intended twenty years of protection.” It also quoted American President Donald Trump as saying, “Our patent system will reward innovation, but it will not be used as a shield to protect unfair monopolies.”

Coming back to ‘patent thicket’ and the same classic case, another report of March 20, 2019 indicated, a new class action lawsuit filed by New York’s largest grocery union has accused AbbVie of violating antitrust and consumer protection laws, which AbbVie has defended by saying that its patent strategy for Humira has protected the investments that are necessary to “advance healthcare.”

Pharma and biotech companies’ maintaining patent monopolies far beyond twenty years has significant consequences on India’s healthcare system. Only patent lawyers and experts can possibly answer whether or not the Indian Patent Law 2005 can effectively deal with the practice of ‘evergreening’ with patent thicket. Intriguingly, taking a cue from recent developments, it seems many pharma and biotech investors too, deem ‘patent thicket’ rather distracting for longer-term undiluted focus on new product development, and sustainable investors’ return.

That apart, the question also comes, whether just as ‘antitrust and consumer protection laws’ in the US, the Competition Law of India will be able to do contain such unfair practices? Otherwise, with MNC lobbyists’ renewed activities in this area, ‘patent thicket’, especially for expensive biologic drugs, will delay market-entry of their cheaper biosimilar versions in India, as well, just as what is happening in the developed nations.

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.

Is India A Success Story With Biosimilar Drugs?

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How Indian generic companies are expanding, if not shifting their business focus on biosimilar and complex generic drugs, may be a current trend of general discourse – but the initiative is not a current one. This journey commenced decades ago with an eye on the future. In those days, Indian players were already dominating the global markets of small molecule generic drugs. Interestingly, it started much before the big global players decided to enter into this segment – especially post patent expiry of large molecule blockbuster drugs.

This strategy not just exhibits a sound business rationale, but also benefits patients with affordable access to biosimilar versions of high cost biologic drugs. In this article, I shall dwell on this subject, basically to understand whether India is a success story with large molecule biosimilar drugs, both in terms of drug development, and also in its commercial performance.

India’s journey began with the dawn of the new millennium:

About two decades back from now, some Indian pharma companies decided to step into an uncharted frontier of large molecule biosimilar drugs. According to the ‘Generics and Biosimilars Initiative (GaBI)’, in 2000 – the first biosimilar drug, duly approved by the Drug Controller General of India (DCGI), was launched in the country.  This was hepatitis B vaccine from Wockhardt – Biovac-B.

I hasten to add, in those years, there were no specific regulatory pathways for approval of large molecule biosimilar drugs in India. Thus, the same marketing approval guidelines as applicable to small molecule generic drugs, used to be followed by the DCGI for this purpose. Specific guidelines for biosimilar drugs were implemented on September 15, 2012, which was subsequently updated in August 2016. To date, around 70 large molecule biosimilar drugs, including biopharmaceuticals, have been introduced in India, as the GaBI list indicates.

It is equally important to note that well before any other countries, domestic pharma companies launched in India, AbbVie’s blockbuster Humira (adalimumab) and Roche’s breast cancer treatment Herceptin (trastuzumab). In this context, it is worth mentioning that US-FDA approved the first biosimilar product, Zarxio (filgrastim-sndz), in March 2015.

Will India be a key driver for global biosimilar market growth?

According to the Grand View Research Report of July 2018, increasing focus on biosimilar product development in countries, such as India, China and South Korea, is a major growth driver of the global biosimilar market. As this report indicates, the global biosimilars market size was valued at USD 4.36 billion in 2016, which is expected to record a CAGR of 34.2 percent during 2018-25 period.

Europe has held the largest revenue market share due to a well-defined regulatory framework for biosimilars was in place there for quite some time, and was followed by Asia Pacific (AP), in 2016. Growing demand for less expensive therapeutic products and high prevalence of chronic diseases in the AP region are expected to contribute to the regional market growth – the report highlighted.

Further, the Report on ‘Country-wise biosimilar pipelines number in development worldwide 2017’ of Statista also indicated that as of October 2017, India has a pipeline of 257 biosimilar drugs, against 269 of China, 187 of the United States, 109 of South Korea, 97 of Russia and 57 of Switzerland. However, post 2009 – after biosimilar regulatory pathway was established in the United States, the country has gained significant momentum in this segment, presenting new opportunities and also some challenges to biosimilar players across the world.

Is Indian biosimilar market growth enough now?

An important point to ponder at this stage: Is Indian biosimilar market growth good enough as of now, as compared to its expected potential? Against the backdrop of India’s global success with generic drugs – right from the initial stages, the current biosimilar market growth is certainly not what it ought to be. Let me illustrate this point by drawing an example from theAssociated Chambers of Commerce of India’s October 2016 White Paper.

According to the Paper, biosimilars were worth USD 2.2 billion out of the USD 32 billion of the Indian pharmaceutical market, in 2016, and is expected to reach USD 40 billion by 2030. This represents a CAGR of 30 percent. A range of biologic patent expiry in the next few years could add further fuel to this growth.

A similar scenario prevails in the global market, as well. According to Energias Market Research report of August 2018, ‘the global biosimilar market is expected to grow significantly from USD 3,748 million in 2017 to USD 34,865 million in 2024, at a CAGR of 32.6 percent from 2018 to 2024.’

Many other reports also forecast that the future of biosimilar drugs would be dramatically different. For example, the ‘World Preview 2017, Outlook to 2022 Report’ of Evaluate Pharma estimated that the entry of biosimilars would erode the total sales of biologics by as much as 54 percent through 2022, in the global markets. It further elaborated that biologic sales may stand to lose up to USD 194 billion as several top blockbuster biologic drugs will go off-patent during this period.

Although, current growth rate of the biosimilar market isn’t at par with expectations, there is a reasonable possibility of its zooming north, both in India and the overseas markets, in the near future. However, I would put a few riders for this to happen, some of which are as follows:

Some uncertainties still exist:

I shall not discuss here the basic barriers that restrict entry of too many players in this segment, unlike small molecule generics. Some of which are – requisite scientific and regulatory expertise, alongside wherewithal to create a world class manufacturing facility a complex nature. Keeping those aside, there are some different types of uncertainties, which need to be successfully navigated to succeed with biosimilars. To get an idea of such unpredictability, let me cite a couple of examples, as hereunder:

1. Unforeseen patent challenges, manufacturing and regulatory issues:

  • Wherewithal to effectively navigate through any unexpected labyrinth of intricate patent challenges, which are very expensive and time-consuming. It may crop up even during the final stages of development, till drug marketing, especially in potentially high profit developed markets, like for biosimilars of Humira (AbbVie) in the United States or for Roche’s Herceptin and Avastin in India.
  • It is expensive, time consuming and risk-intensive to correct even a minor modification or unforeseen variation in the highly controlled manufacturing environment to maintain quality across the system, to ensure high product safety. For example, what happened to Biocon and Mylan with Herceptin Biosimilar. As the production volume goes up, the financial risk becomes greater.
  • There are reports that innovator companies may make access to supplies of reference products difficult, which are so vital for ‘comparability testing and clinical trials.’  This could delay the entire process of development of biosimilar drugs, inviting a cost and time-overrun.
  • Current regulatory requirements in various countries may not be exactly the same, involving significant additional expenditure for overseas market access.

2. User-perception of biosimilar drugs:

Studies on perception of biosimilar vis-à-vis originator’s biologic drugs have brought out that many prescribing physicians still believe that there can be differences between originator’s biologic medicine and their biosimilar equivalents. With drug safety being the major concern of patients, who trust their physician’s decision to start on or switch to a biosimilar, this dilemma gets often translated into doctors’ preferring the originator’s product to its biosimilar version. One such study was published in the September 2017 issue of Bio Drugs. Thus, the evolution of the uptake of biosimilars could also depend mainly on similar perception of physicians.

What happens if this perception continues?

Whereas, the W.H.O and drug regulators in different countries are quite clear about comparable safety and efficacy between the originator’s product and its biosimilar variety, some innovator companies’ position on biosimilar drug definition, could help creating a perception that both are not being quite the same, both in efficacy and safety.

To illustrate this point, let me reproduce below how a top ranked global pharma company - Amgen, defines biosimilar drugs, starting with a perspective of biologic medicines:

“Biologic medicines have led to significant advances in the treatment of patients with serious illnesses.These medicines are large, complex molecules that are difficult to manufacture because they are made in living cells grown in a laboratory. It is impossible for a different manufacturer to make an exact replica of a biologic medicine due to several factors, including the inherent complexity of biologics and the proprietary details of the manufacturing process for the original biologic medicine, often referred to as the reference product.It is because of this that copies of biological products are referred to as “biosimilars”; they are highly SIMILAR but not identical to the biologic upon which they are based.”

Could dissemination of the above concept through a mammoth sales and marketing machine to the target audience, lead to creating a better perception that the originators’ biologic drugs are better than their biosimilar genre?

Other realities:

Despite the availability of a wide array of biosimilar drugs, the prescription pattern of these molecules is still very modest, even in India. One of its reasons, as many believe, these are still not affordable to many, due to high out-of-pocket drug expenses in India.

Thus, where other biosimilars of the same category already exist, competitive domestic pricing would play a critical role for faster market penetration, as happens with small molecule generic drugs.

Another strategic approach to address cost aspect of the issue, is to explore possibilities of sharing the high cost and risks associated with biosimilar drug development, through collaborative arrangements with global drug companies. One good Indian example in this area is Biocon’s collaboration with Mylan.

Conclusion:

The question on whether Indian biosimilar market growth is good enough, assumes greater importance, specifically against the backdrop of domestic players’ engagement in this segment, since around last two decades. Apart from the important perception issue with biosimilars , these medicines are still not affordable to many in India, owing to high ‘out of pocket’ drug expenditure. Just focusing on the price difference between original biologic drugs and their biosimilars, it is unlikely to get this issue resolved. There should be enough competition even within biosimilars to drive down the price, as happened earlier with small molecule generics.

That said, with around 100 private biopharmaceutical companies associated with development, manufacturing and marketing of biosimilar drugs in India, the segment certainly offers a good opportunity for future growth. Over 70 such drugs, most of which are biosimilar versions of blockbuster biologic, are already in the market. Today, Indian companies are stepping out of the shores of India, expecting to make their presence felt in the global biosimilar markets, as they did with generic drugs.

The future projections of biosimilar drugs, both in the domestic and global markets are indeed very bullish. But to reap a rich harvest from expected future opportunities, Indian players would still require some more grounds to cover. Overall, in terms of biosimilar drug development since 2000, India indeed stands out as a success story, but a spectacular commercial success with biosimilars is yet to eventuate.

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.

Innovation: Is Big Pharma Talking Differently?

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“Nearly 2 billion people have no access to basic medicines, causing a cascade of preventable misery and suffering. Good health is impossible without access to pharmaceutical products.” The World Health Organization’s (WHO) ‘Access to Medicine’ report on ‘Ten years in public health 2007–2017’ made this observation.

It also reemphasized: “A significant proportion of the world’s population, especially in developing countries, has yet to derive much benefit from innovations that are commonplace elsewhere.” Despite this, continued lobbying of many pharma companies for TRIPS-plus measures and legislation, the breaching of laws or codes relating to corruption and unethical marketing, and several blatant instances of company misconduct continues, even today.

In the midst of this situation, has Big Pharma started thinking differently about the purpose of innovation? I shall try to explore the ground reality in this article.

The argument of Big Pharma:

In response to the above observation or anything akin to that, Big Pharma has counter arguments, which are rather contentious, as many believe. They generally say, it is the responsibility of the different governments to alleviate health misery of the citizens, and not theirs. In tandem, they keep repeating the same old argument, underscoring lower prices of innovative drugs would lead to lower profit generation, significantly slowing down the process of innovation.

Drug innovation follows an arduous path and an expensive process: 

Big Pharma wants people to comprehend about what it entails in the journey of discovering a New Molecular Entity (NME) and converting it to a safe and effective medicine.

For example, in its booklet Bayer explained: ‘it takes about ten to twelve years to develop a new drug. during this time, highly qualified scientists from a variety of disciplines work on filtering out a suitable active ingredient from an enormous number of compounds. Between 5,000 and 10,000 compounds are rigorously studied in numerous laboratory tests and the best ones further optimized. out of four or five drug candidates that are then tested on humans in clinical studies often only one substance is approved and becomes available to physicians and patients.”

The entire process reportedly takes around 14 years, and according to a 2016 study by the Tufts Center for the Study of Drug Development - developing a new prescription drug, which gains marketing approval, is estimated to cost drug manufacturers USD 2.6 billion. Besides, a new analysis conducted at Forbes finds that getting a single drug to market may involve an expenditure of USD 350 million before the medicine is available for sale. It concludes, large pharmaceutical companies that are working on dozens of drug projects, spend USD 5 billion per new medicine.

Drug innovation is only for those who can afford:

As is being witnessed by many, Big Pharma always tend to argue that high R&D costs drive new drug prices up in pharma. Moving a step further, that drug innovation is for only those patients who can afford, was justified even by the CEO of a major constituent of Big Pharma. An article published in Forbes Magazine on December 05, 2013 wrote: “At the Financial Times Global Pharmaceutical & Biotech Conference this week, Bayer AG CEO, Marijn Dekkers, is reported to have said that Bayer didn’t develop its cancer drug, Nexavar (sorafenib) for India but for Western patients that can afford it.”

How strong is the justification for high new drug cost?   

Instead of believing the pharma argument on its face value, it will be worthwhile to go for a dip-stick analysis. One such analysis, titled “Pharmaceutical industry profits and research and development”, published by the USC-Brookings Schaeffer Initiative for Health Policy on November 17, 2017, presents some interesting facts.

It says, the pharmaceutical industry is a high-fixed-cost and low-marginal-cost industry. This means, as the authors explain, that the cost of bringing a new drug to market is very high and the process is risky, while the cost of producing an extra unit of a product that is on the market is frequently “pennies a pill”. It also, indicates, though there is a disagreement about the exact cost of bringing a new drug to market, there is general recognition that the process costs run a fewhundreds of millions of dollars per new drug. Thus, innovative drugs are supposed to be somewhat more expensive to many patients. But how much – is the question to ponder, I reckon.

An example of a new drug pricing:

Let me choose here, as an example, the pricing of one of the most contentious, but undoubtedly a breakthrough medicine – Sovaldi (Sofosbuvir) of Gilead. Sofosbuvir was discovered in 2007 – not by Gilead Sciences, but by Michael Sofia, a scientist at Pharmasset. The drug was first tested on human successfully in 2010. However, on January 17, 2012 Gilead announced completion of the acquisition of Pharmasset at approximately USD 11.2 billion.

Subsequently, on December 06, 2013, US-FDA approved Gilead’s Sovaldi (Sofosbuvir) for the treatment of Chronic Hepatitis C. Sovaldi was priced at USD 1,000 a day in the U.S., costingUSD 84,000 for a course of treatment. That Gilead can’t justify the price of its hepatitis C therapy – Sovaldi, was highlighted in an article with a similar title, published in the Forbes Magazine on June 17, 2014.

It is worth mentioning that Sovaldi costs around USD 67,000 for a course of therapy, in Germany. Whereas, it costs round USD 55,000 in Canada and the United Kingdom (UK). Gilead has accepted an altogether different pricing strategy for Sovaldi in some other countries, such as India and Egypt.

When the above concept is used to explain Sovaldi pricing:

The above Forbes paper explained its pricing by saying: “Add in other therapies that supplement Sovaldi, and now you’re talking about USD 100,000 or so to treat a single patient. To use Sovaldi to treat each of the 3 million hepatitis C patients in the United States, it would cost around USD 300 billion, or about the same amount we annually spend for all other drugs combined.”

Let me now put a couple of important numbers together to get a sense of the overall pricing scenario of a new drug. The New York Times (NYT) reported on February 03, 2015: “Gilead Sciences sold USD 10.3 billion of its new hepatitis C drug Sovaldi in 2014, a figure that brought it close to being the best-selling drug in the world in only its first year on the market.”

Against its just the first-year sale, let me put the cost of acquisition of Sovaldi at USD 11.2 billion, an expenditure of USD 350 million before the medicine is available for sale as calculated in the Forbes articleand the cost to manufacture a pill of Sovaldi at around USD 130. This reinforces the point, beyond any doubt how ‘outrageous’ its pricing is.Even Gilead’s CEO admitted to failures in setting price of Sovaldi at USD 1,000-A-Pill, said another article on the subject. More important is, the costs to Gilead for Sovaldi acquisition and launch were virtually recovered in just a little over a year, but Sovaldi’s original price tag remains unaltered.

Is the Big Pharma talking differently now?

It appears that some constituents of Big Pharma have now started talking differently in this regard, publicly – at least, in letters, if not in both letter and spirit. Be that as it may, one will possibly be too naïve to accept such sporadic signals coming from pharma, as a shift in their fundamental thought pattern on drug innovation as a profit booster. Being highly optimistic in this area, I would rather say that these are early days to conclude that Big Pharma has really accepted the reality that – drug innovation is only meaningful, if it reaches those patients who need them the most.

Changing…not changing…or early days?

Let me explain this point with examples of changing…not changing…orearly days.

Changing?

On July 24, 2018 during an interview to Pharm Exec the head of the sub-Saharan African region for Roche made some key points, such as:

  • Groundbreaking innovation in medical science is only meaningful, if it reaches the patients who need it.
  • Access to healthcare is a multidimensional challenge and key to addressing the barriers, is really understanding them
  • Need to create a new business model that can sustainably – and this is very important – create access for patients.

Not changing?

When one Big Pharma constituent is showing some change in its approach on the purpose of innovation, another constituent is trying to make the entry of cheaper biosimilar drugs even tougher. This creates yet another doubt – both on safety and efficacy of biosimilars, as compared to much higher priced off-patent original biologic drugs.In August 2018, Pfizer reportedly called for US-FDA guidance on ‘false or misleading information’ about biosimilars, citing some of the following examples from other Big Pharma constituents, such as:

  • Genentech’s “Examine Biosimilars” website, which states that “the FDA requires a biosimilar to be highly similar, but not identical to the existing biologic medicine.” Pfizer argues that Genentech’s omission of the fact that an approved biosimilar must have no clinically meaningful differences from its reference product is a failure to properly communicate the definition of a biosimilar.
  • Janssen Biotech’s patient brochure for brand-name Remicade, which states that a biosimilar works “in a similar way” to a biosimilar without clarifying that the biosimilar must have the same mechanism of action as the originator. Pfizer also takes issue with the brochure’s suggestion that no infliximab biosimilar has been proven to be safe or effective in a switching study.
  • Amgen’s April 13, 2018, tweet that states that patients may react differently to biosimilars than to reference products. Pfizer also points out an Amgen YouTube video that implies that switching to a biosimilar is unsafe for patients who are well controlled on a current therapy.

Interestingly, on July 20, 2018 Pfizer announced that the US-FDA has approved Nivestym (filgrastim-aafi), a biosimilar to Neupogen (filgrastim) of Amgen, for all eligible indications of the reference product. This is the fourth US-FDA approved Pfizer biosimilar drug, the marketing and sales promotion of which expectedly, I reckon, will be no different from other biosimilars.

Early days?

Yes, it appears so. These are early days to draw any definitive conclusion on the subject.

Conclusion:

W.H.O observed in its above report that the ‘overall situation is somewhat improving’. It was also corroborated in the ‘2016 Access to Medicines Index’, which gave high marks to those companies that negotiated licenses for antiretrovirals and hepatitis C medicines through the Medicines Patent Pool (MPP). MPP was set up in 2010 as a public health organization supported by the United Nations to improve access to HIV, hepatitis and tuberculosis treatments in low- and middle- income countries.

It could well be, on the purpose of drug innovation some new realization has dawned, at least, on some few global pharma majors. However, it is still difficult to fathom its depth, at this point of time. There is no conclusive signal to believe that the Big Pharma is now thinking differently on the subject, not just yet.

By: Tapan J. Ray   

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

A ‘Toxin’ Delaying Success of Biosimilar Drugs

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The above comment, although sounds a bit harsh, was made recently by none other than Scott Gottlieb - the Food and Drug Administration Commissioner of the United States. He expressed his anguish while explaining the reasons for a delayed launch of several important biosimilar drugs.

We know, this new genre of drugs has a potential to be a quick game changer, significantly improving access to affordable biologic medicines for many patients. Unfortunately, much desired accelerated progress in this direction, got considerably retarded in the face of a strong headwind, craftily created by the innovator companies, as is widely believed. There are various ways of creating the same. However, the two major ones can be ascribed to:

  • Getting caught in the labyrinth of complex patent challenge.
  • General apprehensions of many doctors on the efficacy and safety of biosimilars as compared to reference drugs.

This is happening in major markets, including India, in varying degree, though.  In this article, I shall deliberate on this issue, starting with the largest pharma market of the world and then focusing on India.

‘Toxin’ that delays biosimilar drug launch:

“Americans could have saved $ 4.5 billion in 2017, if all of the FDA-approved biosimilars were actually available in the United States, instead of getting delayed because of litigations or other agreements.” The Food and Drug Administration Commissioner of the United States – Scott Gottlieb, reportedly, made this comment on July 18, 2018.

Gottlieb referred to some of these as a “toxin” that have prevented other drug makers from launching biosimilar medicines. He accused the manufacturers of pricey biologic medicines of using “unacceptable” anti-competitive tactics to keep competitors off the market. These cost Americans billions of dollars – the report highlighted.

These tactics, as the US FDA commissioner said, are being deliberately used by the innovator pharma and biotech companies and can be corroborated with several examples. One such is the fact that despite the expiration ofthe ‘composition of the matter’ patent for Humira (adalimumab) in December 2016, its ‘non-composition of the matter’ patent would expire not earlier than 2022. The company has therefore made settlement agreements with Amgen and Samsung Bioepis, delaying the launch of adalimumab biosimilars until January 2023.

Protecting own patents Big Pharma challenging rivals’ patents:

Both these are happening for original biologic and biosimilar equivalents, often by the same manufacturers. For example, the Reuters report of October 02, 2016, titled  ‘Big Pharma vs Big Pharma in court battles over biosimilar drugs’ highlighted, although Novartis and Amgen are at each other’s throats in court over the Swiss drug maker’s Enbrel copy, but the two are still cooperating on a drug for migraines.

“One of the biggest surprises has been the number of innovator Biopharma companies, like Amgen, now developing biosimilars to compete with the products of other innovator companies,” the article observes. It also reports that Sanofi, Merck, Eli Lilly, Pfizer, Johnson & Johnson and Biogen are also embroiled in lawsuits over biosimilars.

This trend vindicates that the line dividing makers of brand-name drugs and copycat medicines is blurring as companies known for innovative treatments queue up to peddle copies of rivals’ complex biological medicines, Reuters noted. Consequently, they are now doing both – protecting their high-price products from biosimilars drugs,while simultaneously challenging rivals’ patent claims.

There is another interesting side to it. Notwithstanding, biosimilars are a cost-effective alternative to biologic drugs that could improve patients’ access to expensive biological medicines, prescribers’ perception of biosimilar medicines are still not quite positive, just yet.

Doctors’ attitude on biosimilar prescription:

To illustrate this point, let me quote from recent research findings in this area. One such is the May 2017 study on “Medical specialists’ attitudes to prescribing biosimilars.” The key points are as follows:

  • Between 54 and 74 percent of the specialists are confident in the safety, efficacy, manufacturing and Pharmacovigilance of biosimilars.
  • 71 percent of specialists agreed that they would prescribe biosimilars for all or some conditions meeting relevant clinical criteria.
  • Specialists are less confident about indication extrapolation and switching patients from an existing biologic.
  • The most common situations that they would not prescribe a biosimilar was where there was a lack of clinical data supporting efficacy (32 percent), or evidence of adverse effects.

Overall, medical specialists held positive attitudes towards biosimilars, but were less confident in indication extrapolation and switching patients from the original biologic. Several experts believe that constantly highlighting the fear factors against biosimilar drugs, such as possible risks of interchangeability with reference product, or immunogenicity related serious consequences, though very rare, are fueling the fire of apprehensions on the wide use of biosimilar medicines.

However, several reviews, like the one that I am quoting here finds that ‘switching from the reference product to related biosimilar drug is not inherently dangerous.’I discussed this issue, with details in one of my articles, published in this blog on July 31, 2017.

Any therapeutic difference between the original biologic and biosimilars?

As the US-FDA says: “Patients and their physicians can expect that there will be no clinically meaningful differences between taking a reference product and a biosimilar drug when these products are used as intended. All reference products and biosimilar products meet FDA’s rigorous standards for approval for the indications (medical conditions) described in product labeling.”

The key point to take note of is that the US drug regulator categorically reiterates: “Once a biosimilar has been approved by the FDA, patients and health care providers can be assured of the safety and effectiveness of the biosimilar, just as they would for the reference product.”

The invisible barriers to biosimilar drugs in India:

Although, there are no specific data requirements for interchangeability of biosimilar drugs with the reference product, as mentioned in the latest Indian Guidelines on similar biologic, other visible and visible barriers are restricting the rapid growth of drugs belonging to this genre.

An interesting research study finds, like many other drugs, the cost of biosimilars is a major barrier to the rapid growth of the market in India. The Deloitte Report, titled “Winning with biosimilars: Opportunities in global markets” also articulated: “Approximately 70 percent of the country’s population is considered rural and will focus on the cost of therapy – a 20-30 percent discount on originator biologics may not be sufficient.”

Moreover, many patients who are on original biologic drugs, costing higher than related biosimilars and want to switch over to affordable equivalents, are not able to do so. In many cases, doctors’ do not encourage them to do so, for various reasons, including the general assertion that original biologic drugs are more effective. India being considered as the global capital of diabetes, let me cite an example from this disease area, just to drive home the point.

A recent experience on biosimilar drug interchangeability in India:

Just the last week, I received a call from a friend’s wife living in Delhi who wanted to know whether Lantus 100 IU/ml of Sanofi can be replaced with Glaritus 100 IU/ml of Wockhardt, as the latter costs much less. I advised her to consult their doctor and request accordingly. She said, it has already been done and the doctor says Lantus is a better product.

To get a fact-based idea on what she told me, I referred to two circulars of the National Pharmaceutical Pricing Authority (NPPA) – one for Glaritus and the other one for Lantus and found that both are under drug price control and have respective ceiling prices. As both the circulars are of 2009, these may probably be treated as an indicative price difference. NPPA notified price for a 3 ml cartridge of Glaritus reads as Rs.135. 24. Whereas, the same for Lantus was mentioned as Rs.564.84.

Is an original biologic generally superior to Indian biosimilars?

US-FDA has already reiterated, “Once a biosimilar has been approved by the FDA, patients and health care providers can be assured of the safety and effectiveness of the biosimilar, just as they would for the reference product.”

However, to get India-specific, evidence-based information in this area, I checked, whether Lantus has any clinically proven therapeutic superiority over Glaritus. Interestingly, I came across the results of a 12-week study concluding that biosimilar insulin glargine, Glaritus, is comparable to the reference product, Lantus – providing a safe and effective option for patients with T1DM. Nevertheless, the researchers did say that more studies are required in this area.

The core question that needs to be addressed why is the doctor’s perception so different and the reasons for the same?

Conclusion:

In view of all that has been discussed in this article, I find it challenging to fathom that in the absence of any credible and conclusive specific study, how could a doctor possibly infer that higher priced imported original biologic drugs are generally superior to lower priced biosimilar equivalents? More so, when in India, there are no regulatory issues on interchangeability between original biologic and its biosimilar equivalent.

Or for that matter, a branded generic product is superior to all other equivalent generic drugs without a brand name? This can happen, especially when the vested interests actively work on ensuring that such a perception gains ground, boosting the sales revenue and mostly at the cost of patients’ interest.

As one would witness in many other spheres of life that creating a blatantly self-serving, positive target audience perception, by any means, primarily aimed at destroying the same of others, is assuming increasing importance. Are we seeing the reflection of the same, even in the field of evidence based medical science?

I reckon, it raises a flag for all to ponder, particularly after reading the recent candid comments of the US-FDA commissioner, as quoted above.

Could this be one of those ‘Toxins’, which delays success of biosimilar drugs?

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.