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Making New Cancer Drugs Cost-effective

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The prices of new cancer drugs are increasingly becoming unsustainable across the world, and more so in India. A sizable number of poor and even middle-income patients, who spend their entire life’s savings for the treatment of this dreaded disease, is pushed towards extreme economic hardship. Their plight in India would continue to remain so, till Universal Health Care (UHC) comes into force, as enunciated in the National Health Policy 2017.

Thus, the delivery of affordable and equitable cancer care poses one of India’s greatest public health challenges. Public expenditure on cancer in India remains below US$ 10 per person, as compared with more than US$ 100 per person in high-income countries. The May 2014 paper, published in ‘The Lancet Oncology’, analyzed this concern in detail.

In this article, after giving a brief backdrop, I shall explore a possible alternative to make cancer treatment with new drugs affordable to many by scaling up this strategic option.

Cancer – the second leading cause of death:

According to the World Health Organization (W.H.O), cancer is the second leading cause of death globally and accounted for 8.8 million deaths in 2015. This works out to nearly 1 in 6 of all global deaths, with US$ 1.16 trillion being the estimated total annual economic cost of cancer in 2010. Lung, prostate, colorectal, stomach and liver cancer are the most common types of cancer in men, while breast, colorectal, lung, cervix and stomach cancer are the most common among women. To reduce significant disability, suffering and deaths caused by cancer worldwide, effective and affordable programs in early diagnosis, screening, treatment, and palliative care are needed. Treatment options may include surgery, medicines and/or radiotherapy – the report reiterates. In many instances, anti-cancer drugs are the mainstay treatment.

For the country, Indian Council of Medical Research (ICMR) reported over 736, 000 people succumbing to the disease in 2016. This figure is expected to shoot up to 880,000 by 2020. ICMR estimated the total number of new cancer cases at around 1.45 million in 2016, and the same is likely to reach 1.73 million by 2020. The situation in this area, therefore, rather grim across the world, including India.

Cancer treatment cost in India is one of the highest in the world:

Anticancer drugs are generally expensive. As stated in a related article, published in the Nature Reviews Clinical Oncology on March 14, 2017, in the United States, a novel anticancer drug routinely costs more than US$ 100,000 per year of treatment. When adjusted for per capita spending power, these lifesaving medicines become most unaffordable in economically developing nations, such as India and China. Not only are their launch prices high and fast rising, but these also often escalate during the respective patent exclusivity period.

That in terms of the ability to pay for drugs, cancer drugs are most affordable in Australia and least affordable in India and China, was established in one of the largest research study presented at the 2016 Annual Meeting of the American Society of Clinical Oncology. Moreover, even in those cases where cancer could be detected early, about half the patients in India are compelled to skip the treatment for high drug cost, highlights another article.

Interestingly, the concerned drug manufacturers seldom, if at all, justify such astronomical drug prices and subsequent price increases well supported by some rational factors, such as, the extent of benefit patients are likely to derive, the novelty of the agents, or detailed spending on research and development, the above paper states.

The increasing trend of price escalation of cancer drugs harms many patients, often directly, through increased out-of-pocket expenses, which reduce levels of patient compliance, or drive thousands of cancer patients skipping the drug treatment, altogether. Consequently, it also harms the society by imposing cumulative price burdens on many patients that are unsustainable.

Despite high cost, annual global spending on anticancer drugs has already exceeded US$100 billion, and is predicted to reach US$150 billion by 2020. In India too, oncology is a leading therapeutic segment, which reached a turnover of Rs. 2,000 Crore (around US$ 320 million) in 2013 and is expected to grow to Rs. 3,831 crore (around US$ 615 million) by the end of 2017, according to a report of Frost and Sullivan.

The reason for high drug price:

The real reason for the high cost of cancer drugs, just as many other life-saving medicines, is quite challenging to fathom. Many attribute its reason to unsustainable R&D models of the global pharma companies, in general.

For example, “the spiraling cost of new drugs mandates a fundamentally different approach to keep lifesaving therapies affordable for cancer patients” – argued an article titled, “How Much Longer Will We Put Up With US$ 100,000 Cancer Drugs?”, published by Elsevier Inc. In the same context, another article titled “Making Cancer Treatment More Affordable”, published in the ‘Rare Disease Report’ on Feb 09, 2017, reiterated that the current R&D model needs to change, as the cost of many such treatments is higher than the cost of an average person’s house in the United States.

Nonetheless, the drug manufacturers answer this difficult question with ease and promptness, citing that the cost of innovation to bring these drugs through a complex research and development (R&D) process to the market, isn’t just very high, but is also increasing at a rapid pace.

Pharma R&D cost:

An analysis by the Tufts Center for the Study of Drug Development, published in the Journal of Health Economics in March, 2016 pegged the average cost to develop and gain marketing approval for a new drug at US$ 2.558 billion. It also said that the total cost of innovation of a new drug and bringing it to market, has increased more than double from US$ 1.22 billion in 2003 to US$ 2.6 billion in 2014. Although these numbers are being vehemently challenged in several credible journals and by the international media, many global pharma majors justify the high new drug prices

by highlighting that developing a new molecule takes an enormous amount of time of 12 to 14 years, lots of financial resources and huge efforts.

On the other hand, an article titled, “Does it really cost US$ 2.6 billion to develop a new drug?”, published in The Washington Post on November 18, 2014 observed that: ‘The never-ending debate about what drugs should cost is in part driven by the fact that no one seems to know what it actually costs to develop one.”

But, why is the decline in the R&D productivity trend?

According to a 2014 review article titled, “Recent Advances in Drug Repositioning for the Discovery of New Anticancer Drugs”, published in the International Journal of Biological Sciences, while the total R&D expenditure for drug discovery worldwide increased 10 times since 1975 (US$ 4 billion) to 2009 (US$ 40 billion), the number of NMEs approved has remained largely flat (26 new drugs approved in 1976 and 27 new drugs approved in 2013). The average time required for drug discovery to market launch has also increased over time in the US and in the EU countries from 9.7 years during 1990s, to 13.9 years from 2000 onwards.

Be that as it may, the bottom-line is regardless of tremendous advancement in biological science, technology and analytics, especially in the new millennium, coupled with increasing investments in pharma R&D, the total number of NMEs that has reached the market hasn’t shown commensurate increase.

One of my articles published in this blog titled, “How Expensive Is Drug Innovation?” found an echo of the same in a globally reputed journal. This study, published by the BMJ on May 2016, titled “Propaganda or the cost of innovation? Challenging the high price of new drugs”, expressed deep concern on the rising prices of new medicines. It reiterated that this trend is set to overwhelm health systems around the world.

Need for an alternative R&D strategy:

The hurdles in discovering and developing new drugs call for alternative approaches, particularly for life threatening diseases, such as cancer. I reckon, it’s about time to scale-up a viable alternative strategy to bring down the R&D cost of new drugs, improve the success rate of clinical development, reduce a decade long ‘mind to market’ timeframe for an innovative drug or a treatment, and of course, the mind blogging cost of the entire process, as asserted in the above report from the Tufts Center.

One such alternative strategy could well be: ‘Drug Repurposing’

Drug Repurposing:

As defined by the National Center for Advancing Translational Sciences, ‘drug repurposing’ “generally refers to studying drugs that are already approved to treat one disease or condition to see if they are safe and effective for treating other diseases”.

As many molecules, with well-documented records on their pharmacology and toxicity profile, have been already formulated and undergone large clinical trials on humans, repurposing those drugs building upon the available documents and experiences for fresh clinical trials in different disease conditions, would hasten the regulatory review process for marketing approval, and at a much lesser cost.

I shall quote here just two such examples of ‘drug repurposing’ from well-known molecules, as follows:

  • Sildenafil (Viagra): The blockbuster drug that was launched by Pfizer in 1998 for the treatment of erectile dysfunctions was originally developed for the treatment of coronary artery disease by the same company in 1980s.
  • Thalidomide: Originally designed and developed by a German pharmaceutical company called Grünenthal in Stolberg as a treatment for morning sickness in 1957, but was withdrawn in 1961 from the market because it caused birth defects. The same molecule was reintroduced in 1998 as a ‘repurposed drug’ to effectively treat patients with erythema nodosum leprosum (ENL) – a complication of leprosy, and multiple myeloma – a type of cancer.

I had given many more examples of ‘drug repurposing’ in one of my earlier articles published in this blog.

Repurposing drugs for cancer:

The above-mentioned review article of International Journal of Biological Sciences 2014 clearly noted: “Drug repositioning has attracted particular attention from the communities engaged in anticancer drug discovery due to the combination of great demand for new anticancer drugs and the availability of a wide variety of cell and target-based screening assays. With the successful clinical introduction of a number of non-cancer drugs for cancer treatment, ‘drug repurposing’ now became a powerful alternative strategy to discover and develop novel anticancer drug candidates from the existing drug space.”

The following are some recent successful examples of ‘drug repurposing’ for anticancer drug discovery from non-cancer drugs, which are mostly under Phase I to II clinical trials:

Drug Original treatment Clinical status for cancer treatment
Itraconazole Fungal infections Phase I and II
Nelfinavir HIV infections Phase I and II
Digoxin Cardiac diseases Phase I and II
Nitroxoline Urinary Tract Infections Preclinical
Riluzole Amyotropic lateral sclerosis Phase I and II
Disulfram Chronic alcoholism Phase I and II

‘Drug repurposing’ market:

A January 2016 report by BCC Research estimates that the global market for drug repurposing will grow from nearly US$ 24.4 billion in 2015 to nearly US$ 31.3 billion by 2020, with a compound annual growth rate (CAGR) of 5.1 percent for the period of 2015-2020.

Expressing concern just not enough:

There are enough examples available across the world regarding stakeholders’ expression of great concern on this issue, with the buzz of such protests getting progressively shriller.

However, in India, high prices of cancer drugs do not seem to be a great issue with the medical profession, just yet, notwithstanding some sporadic steps taken by the National Pharmaceutical Pricing Authority (NPPA) to allay the economic burden of cancer patients to some extent. Encouragingly, the top cancer specialists of the American Society of Clinical Oncology are reportedly working out a framework for rating and selecting cancer drugs not only for their benefits and side effects, but prices as well.

In a 2015 paper, a group of cancer specialists from Mayo Clinic also articulated, that the oft-repeated arguments of price controls stifle innovation are not good enough to justify unusually high prices of cancer drugs. Their solution for this problem includes value-based pricing and NICE like body of the United Kingdom. An interesting video clip from Mayo Clinic justifies the argument.

All this can at best be epitomized as so far so good, and may help increase the public awareness level on this subject. However, the moot point remains: Has anything significantly changed on the ground, on a permanent basis, by mere expression of such concerns?

Conclusion:

This discussion may provoke many to go back to the square number one, making the ongoing raging debate on Innovation, Intellectual Property Rights (IPR) and Public Health Interest to gather more steam, but the core concern continues to remain unresolved.

I hasten to add that all such concerns, including strong protests, may no doubt create some temporary pressure on drug manufacturers, but they are experienced enough to navigate through such issues, as they have been doing, so far. However, for making new cancer drugs cost-effective for a vast population of patients, coming out of the current strategic mold of pharma research and development would be necessary. Grant of Compulsory License (CL), or the expectation of the local drug manufacturers for a Voluntary License (VL) of new cancer drugs, can’t be a routine process either, as it appears unrealistic to me, for various reasons.

I have discussed in this article just one alternative R&D strategy in this area, and that is Drug Repurposing (DR). There could be several others. DR is reportedly gaining increasing focus, as it represents a smart way to exploit new molecular targets of a known non-oncological drug for a new therapeutic applications in oncology. Be that as it may, pharma companies and the academia must agree to sail on the same boat together having a common goal to make new cancer drugs cost-effective for majority of cancer patients struggling hard, for life.

I would conclude this article quoting the President and Chief Science Officer of Illinois-based Cures Within Reach who said: “What I like about drug repurposing is that it can solve two issues: improved health-care impact and reduced health-care cost – That’s a big driver for us.”

By: Tapan J. Ray

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

The Power Of Color And Design In Pharma Branding

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On November 06, 2015, the District Court of Delaware of the United States (US) passed a temporary restraining order barring Dr. Reddy’s Laboratories (DRL) from selling in the US its generic version of AstraZeneca’s blockbuster anti-ulcerant drug Nexium, with immediate effect. 

This temporary order came in response to the petition moved by the drug innovator – AstraZeneca, objecting to the use of purple color in DRL’s generic equivalent of Nexium, launched in September 2015.

According to an estimate, this generic formulation could fetch a post tax profit of around US$25 to US$35 million to DRL in 2016. Nevertheless, the Delaware court order is pending a further hearing. The court has also asked both the companies to suggest the next course of action.

When color becomes an integral part of brand value creation: 

AstraZeneca’s effective branding of ‘purple color pills’ Nexium and Prilosec has helped the company to obtain this temporary restraining court order, which states: 

“As a result of such promotional efforts, there is undisputed evidence that the media and the public associate the color purple with AstraZeneca and its Prilosec and Nexium products.”      

The Court observed, though DRL product is not identical to AstraZeneca’s Nexium, still could confuse patients due to its association with the purple color.

In this context, it is worth noting, though a couple of other generic Nexium capsules are available in the US, none is purple in color. Teva’s capsules are green and blue and Mylan’s are white in color.

Can a right be established on branding ‘color’?

It appears so. In its Complaint to the Court against DRL, AstraZeneca (AZ) argued in favor of its successful branding of Nexium with ‘Purple Color, as follows:

  • AZ brand has offered relief to sufferers of severe heartburn and other disorders caused by stomach acid reflux through its “Purple Pills” Prilosec® and Nexium®, known as “The Purple Pill®.”
  • AZ has devoted significant resources over the years to advertise and promote its Prilosec® and Nexium® purple pills using the ‘look for’ purple advertising.                                                 
  • The preference for purple was purely for branding purposes—purple contributes nothing to the safety or efficacy of AZ’s products. 
  • AZ has continuously sold Nexium® from 2001 to present in purple colored capsules with either two or three gold-colored bands displayed on the purple capsules.
  • Thus, AZ’s Purple Pills have been famous for many years through extensive advertising both to doctors and patients and extensive publicity, among other reasons. 
  • If DRL is not enjoined from using the color purple, DRL’s purple generic pills are likely to cause confusion among consumers and others and are likely to dilute the distinctiveness of AZ’s federally registered purple color trademarks. 
  • DRL’s attempt to free-ride off the fame of AZ’s famous Purple Pills poses imminent irreparable harm to both AZ and the public if not enjoined.

I would like to remind the readers at this point that Pfizer also did branding of Viagra keeping the color of the pill as one of the key ingredients, as it is also well-known as the ‘Blue Pill’, across the world.

Does color of the pill matter to patients? 

In this regard, on July 15, 2014, an interesting study titled, “Burden of Changes in Pill Appearance for Patients Receiving Generic Cardiovascular Medications After Myocardial Infarction”, published in the journal of ‘Annals of Internal Medicine’, wanted to find out whether non persistent use of generic drugs among patients with cardiovascular disease after Myocardial Infarction (MI) is associated with the inconsistent appearance of their medications.

The study concluded, “Variation in the appearance of generic pills is associated with the nonpersistent use of these essential drugs after MI among patients with cardiovascular disease.”

Or in other words, the researchers found, 30 percent or more patients are likely to stop taking their medication because the unexpected change, can be confusing.

Impact of a branding strategy with color and design as integral parts: 

Even after a product goes off-patent, ‘Intellectual Property Rights (IPR)’ could still protect aspects of a pill design, which are not associated with product functioning.

The above study finds that in true sense, the shape and color of the tablets or capsules are very much intimately associated with the functional aspect of the product, as these characteristics established through effective branding exercise of the original product, help promoting patient compliance to various drugs, which is so important in combating serious ailments.

Effective branding with extrinsic factors: 

The above important research finding clearly establishes that even the extrinsic product features like, color and design, when used in an effective branding strategy, could have critical medical relevance for the patients.

Such clever pharma branding strategies are not just restricted to:

  • AstraZeneca’s “little purple pill” – Nexium
  • Or Pfizer’s “blue-diamond-shaped tablet” – Viagra.

There are many other examples of making extrinsic product features as effective branding tools. A few of these are as follows:

  • GlaxoSmithKline’s craftily designed a “tilt-tab” for its Parkinson’s disease brand Requip. This design makes it easier for the patients to pick up the tablets. Requip “tilt-tab” has been modeled with unconventional 5 sides and a pointed fulcrum that prevents it from lying flat.
  • Diovan blister packs of Novartis with calendar markings for pills, improved patient compliance significantly, as a research study established.
  • Special caps are now reportedly available that fit on most prescription drug bottles, containing a wireless chip that communicates with a light plug. The cap pulses orange light, when the patient forgets to take a pill.

An article published in the ‘Outsourcing-Pharma.com’ on March 11, 2014 states, Philadelphia based Colorcon, that works with many pharma manufacturers, both innovator and generic players, to shape and coat their tablets, has a library of 40,000 different colors and shapes of samples to choose from.

The color and design war in pharma branding has just begun: 

The importance of color and design as a pharma brand identity has started being realized today. The latest DRL case involving the color of AstraZeneca’s Nexium, close on the heels of similar other cases related to the blue color of Pfizer’s Viagra, has thrown open a critical question.

This query wants a specific answer, whether IP protection on Trademark would get extended to distinctive colors, which through branding initiatives have become strongly associated with a specific brand. Possibly the unprecedented lawsuit on the subject by AstraZeneca against DRL would ultimately settle the legal aspect of the issue, decisively.

Nevertheless, the importance of color and design as two key ingredients of successful pharma branding would remain unchallenged from ‘creative marketing’ stand point.

Conclusion:

There are market research studies that suggest that around 80 percent of visual information for any brand is related to color and design. Pharmaceuticals are no exceptions. Thus, these important extrinsic product features can be strategically leveraged with the intrinsic product benefits in a branding exercise, to create a cutting edge value synergy.

In today’s environment of innovative branding strategy, the state of art tablet color and design technologies may be appropriately utilized by the pharma players to successfully build and also to get limited brand protection, as happened in the case of Nexium of AstraZeneca.

The research findings, as mentioned above, that such type of branding has important medical relevance too, may be construed as an additional silver lining to this exciting process.

In my view, the aforesaid strategy would make enormous sense for branded generic drugs too, though with tailor-made approaches, which could well be a different discussion altogether.

Keeping all this in perspective, I reckon, innovative use of the power of color and design in pharma ‘branding’ exercise, including a comprehensive communication strategy with appropriate platforms, could provide an important leading edge for significant commercial success of a brand.

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.