A set of perplexing questions on the drug industry has been haunting many, since long. One such area is intimately associated with the core purpose of this business, as enunciated by each company, often publicly. Just to give a feel of it, let me quote what one of the largest global pharma players – Pfizer articulated in this regard, on April 5, 2019: “Health for All is at the core of our company’s purpose. We advance breakthroughs that change patients’ lives by ensuring they have access to quality health care services and Pfizer’s medicines and vaccines.”

Publicly expressed core purpose of any pharma business being generally similar, it may be construed as the same of the industry, at large. Hence, some baffling questions – not ethical, but purely commercial in nature, float at the top of mind, such as:

• How the core purpose of business – “Health for All”, gets served when companies bring to the market mostly exorbitantly high-priced drugs, having access only to a minuscule patient population?

• How are these companies growing at a faster pace and doing better commercially, by focusing more on orphan drugs approved for the treatment of rare diseases, affecting a very small patient population.

At this point, it will be worthwhile to have a quick recap on ‘orphan drug’ and ‘rare disease’. According to MedicineNet, orphan drugs are those which are developed to specifically treat rare medical condition. This rare medical condition is also referred to as an orphan disease. With that preamble, I shall now focus on this knotty area in search of evidence-based answers to – Is it possible to reap a rich harvest in business with orphan drugs for rare disease? And, if so, how?

Is the focus on high priced orphan a strategic business move?

Regardless of an affirmative or negative answer to the above questions, many people are head scratching with anguish while observing this trend in the drug industry. Mainly because, it is possibly the most important industry for most patients, not only while suffering from an ailment, but also before and after it happens, for various reasons.

The anguish increases manifold, when top manufacturers of popular mass-market drugs, such as, the cholesterol blockbuster Crestor, Abilify for psychiatric conditions, cancer drug Herceptin, and rheumatoid arthritis drug Humira, the best-selling medicine in the world, at a later stage seek and receive orphan drug status for these products reaping a rich harvest. The underlying intent being leveraging ‘additional advantages’ for exorbitant pricing and lesser competition. Hence, it is a strategic business move. I shall discuss this point in greater details, as was raised in a Kaiser Health News (KHN) investigation, in this article.

The same feeling gets resonated in several articles and papers, such as the one titled ‘Big Pharma’s Go-To Defense of Soaring Drug Prices Doesn’t Add Up,’ published in The Atlantic on March 23, 2019. It questioned, ‘How is it that pharmaceutical companies can charge patients $100,000, $200,000, or even $500,000 a year for drugs – many of which are not even curative?’ Nonetheless, the strategy is working well, as we shall find below.

More drugs for rare diseases entering the market at a higher price:

Another article, titled ‘Drug Prices for Rare Diseases Skyrocket While Big Pharma Makes Record Profits,’ published by America’s Health Insurance Plans (AHIP) on September 10, 2019 wrote, drugs for rare diseases are now entering the market at higher prices than ever before, ranging from tens-of-thousands to hundreds-of-thousands of dollars per patient. It further wrote, according to a new report by AHIP, ‘out-of-control drug prices mean too many patients are forced to choose between paying for their prescriptions or paying their mortgage. The prices for drugs to treat rare medical conditions are 25 times more expensive than traditional drugs. That is 26-fold increase in two decades.

The rationale behind so high pricing:

To explore the rationale behind the exorbitant pricing of such drugs, let’s examine what the expert organizations, such as the Tufts Center for the Study of Drug Development (CSSD) said in this regard. Quoting a senior research fellow of CSDD, the article - ‘The High Cost of Rare Disease Drugs,’ published by the Genetic Engineering & Biotechnology News (GEN) on March 04, 2014 reported, although biopharma players generally set higher prices for orphan drugs, there is no causal link between cost of development and pricing. Instead, rare-disease drug prices reflect typical supply and demand situation: ‘Few treatment alternatives allow companies to charge what they can, knowing that payers will often ultimately foot the bill.’

It further explained: “The rarity of the disease means that few people are affected. Generally, the fewer disease sufferers there are, the higher the price of the drug. Companies that invest the same amount of money or more in orphan drugs as they would non-orphan drugs, want to recoup their investment.”

The situation in India for such drugs:

The January 05, 2019 issue of The Pharma Letter captures it all in its headline – ‘India lifts price caps on innovative and orphan drugs; major fillip for Big Pharma.’ It said, with the new legislation announced on January 4, 2019, the Indian government has decided to remove price restrictions on new and innovative drugs developed by foreign pharmaceutical companies for the first five years. In a rider, the government notification also states, the provisions of the Drug Price Control Order (DPCO) 2013 will not apply to drugs for treating orphan diseases (rare diseases).

How will it impact Indian patients?

Consequent to the above government decision, as the report indicated: ‘Orphan drugs to treat rare disease, like Myozyme (alglucosidase alfa) and Fabrazyme (agalsidase beta), both from Genzyme, which are used in the treatment of rare genetic diseases, are among a host of medicines that are to be kept out of price control.’

Quoting officials, the paper pointed out, the most challenging part in the fight against rare diseases is access to affordable treatment. As on date, the prices of these drugs tend to vary, e.g., the cost of treatment with enzyme replacement therapies may reach more than $150,000 per treatment per year. Whereas, in some other areas it may even be as much as $400,000 annually. Moreover, most of these drugs are rarely available in India. As a result, Indian patients suffering from rare diseases have to import these drugs directly. This makes affordability of medicines with an orphan drug regulatory status, a major issue for different stakeholders.

Why patient groups are not generally too vocal about this issue?

An interesting paper of 2008-09 brought to the fore the importance of patient organizations to further patient interest in various areas of health care. With the example of rare diseases and orphan drugs, it aptly expressed: ‘by changing the scale of their organizational efforts, patients’ organizations have managed to integrate themselves into the relays of power through which matters of health are thought about and acted upon. Through their formation into coalitions, patients’ organizations have been able to assume a number of important functions in relation to the government of health.’ The paper further added that the orphan drug problem can be thought of as having changed the scale and organizational form of rare disease patients’ groups.

Regrettably, a recent report of October 09, 2019, raised a big question in this area with a startling headline - ‘Big Pharma’s shelling out big-time to patient organizations. Is there any quid pro quo?’ It said, the Senate Finance Committee of the United States, while looking into the drug pricing decisions, ‘is digging into pharma funding for patient advocacy groups, which have been known to speak in tune that are music to the industry’s ears.’ It added, some Big Pharma constituents together contributed more than $ 680 million to hundreds of patient groups and other nonprofits last year.

It’s worth noting, earlier this year, several patient advocacy groups rallied in objection to a Trump-administration plan that would introduce step therapy requiring patients to try cheaper drugs before moving to more costly ones. ‘A Kaiser Health News analysis found that about half of the groups that objected had received funding from the pharmaceutical industry.’ Be that it may, rallying behind high drug prices by patient groups would help the industry only at the cost of patients’ interest. This is beyond an iota of doubt.

The motivation behind marketing more drugs for rare diseases:

There are several motivating factors to market drugs, which also treat rare disease, attaching startling price tags. The top drivers are generally considered, as follows:

• The company gets seven years of market exclusive rights with the drug marketing approval for a rare or orphan disease. Interestingly, many drugs that now have an orphan status aren’t entirely new, either. Even if, the product patent runs out, USFDA won’t approve another version to treat that rare disease for seven years. This exclusivity is compensation for developing a drug, designed for a small number of patients whose total sales weren’t expected to be that profitable, otherwise.

• Market exclusivity rights granted by the ‘Orphan Drug Act’ in the United States, can be a vital part of the protective shield that companies create.

• Leveraging associated free pricing incentive, the concerned company can attach any price tag of its choice to the orphan drug, sans any competition.

• Interestingly, more than 80 orphan drugs won USFDA approval for more than one rare disease, and in some cases, multiple rare diseases. For each additional approval, the drug manufacturer is qualified for a fresh batch of incentives. 

The system ‘is being manipulated by many drug makers’:

That this system is being manipulated by many drug makers was also established by the Kaiser Health News (KHN) investigation dated January 17, 2017 titled, ‘Drugmakers Manipulate Orphan Drug Rules To Create Prized Monopolies.’ The analysis brought out that ‘the system intended to help desperate patients, is being manipulated by most drug makers. It reiterated, the key driver is to maximize profits, besides protecting niche markets for even those medicines, which are already being taken by millions. Thus, many orphan drugs, originally developed to treat diseases affecting fewer than 200,000 people, come with astronomical price tags.’

Even some familiar brands were later approved as orphan drugs:

The KHN’s investigation also uncovered that many drugs that now have an orphan status aren’t entirely new. Over 70 were drugs first approved by the USFDA for mass market use. These medicines, some with familiar brand names, were later approved as orphans. ‘In each case, their manufacturers received millions of dollars in government incentives plus seven years of exclusive rights to treat that rare disease, or a monopoly’, the investigation revealed.

The same KHN study also cited the example of AbbVie’s Humira – the best-selling drug in the world. ‘Humira was approved by the USFDA in late 2002 to treat millions of people who suffer from rheumatoid arthritis. Three years later, AbbVie asked the FDA to designate it as an orphan to treat juvenile rheumatoid arthritis, which they told the FDA affects between 30,000 and 50,000 Americans. That pediatric use was approved in 2008, and Humira subsequently was approved for four more rare diseases, including Crohn’s and uveitis, an inflammatory disease affecting the eyes. The ophthalmologic approval would extend the market exclusivity for Humira for that disease until 2023, the report highlighted.

The report also indicated, much touted Gleevec of Novartis, a drug that revolutionized the treatment of chronic myeloid leukemia, has nine orphan approvals. Similarly, Botox, started out as a drug to treat painful muscle spasms of the eye and has three orphan drug approvals. It’s also approved as a drug for mass-market for a variety of ailments, including chronic migraines and wrinkles. Despite humongous pricing, recent reports show that drugs with orphan status are eclipsing many new drugs with outstanding commercial success.

Companies focus on orphan drugs for better financial results:

Many top global companies’ sharp strategic focus on orphan drugs, presumably for the above reasons, is paying a rich dividend. This is evident from a number of recent reports, such as, ‘Orphan Drug Report 2019’ of Evaluate Pharma, released in April. The report says, orphan drugs will make up one-fifth of worldwide prescription sales, amounting to $242bn in spending by 2024 – much of it is going to either big pharma or big biotech players. It also found that the drugs prescribed for the treatment of rare diseases now account for seven of the 10 top-selling drugs of any kind, ranked by annual sales.

Another study of October 2019 by Prime Therapeutics LLC (Prime) shows, with more of ultra-expensive drug treatments coming to market, there is a sharp jump in the number of drug super spenders. While small in number, this group of drug super spenders grew 63 percent, which resulted in $800 million in additional drug costs. In the same period, the number of drug super spenders with drug costs over $750,000 increased 38 percent. This explains, why many companies are focusing on orphan drugs for better financial results.

Conclusion:

As the above quoted report of AHIP articulated, the regulators’ primary intent behind creating lucrative incentives for orphan drugs, was to encourage drug makers to develop treatments for rare diseases by earning a modest profit. ‘Unfortunately, drug makers have responded by building lucrative business models that empower them to achieve a gross profit margin of more than 80 percent – compared to an average gross profit margin of 16 percent for the rest of the pharmaceutical industry,’ the report said.

The AHIP study also finds, from 1998 to 2017, orphan drugs were 25 times more expensive than non-orphan drugs, resulting 26-fold increase in average per-patient annual cost, while the cost of specialty and traditional drugs merely doubled. Today, 88 percent of orphan drugs cost more than $10,000 per year per patient, which will be no different even when Indian patients import the same. The paper also revealed, in 2017, seven out of ten best-selling drugs had orphan indications. And among newly launched drugs, the share of orphan drugs increased more than 4-fold, from 10 percent to 44 percent, over a 20-year period.

Coming back to the core purpose of the pharma and biotech business, as defined by the pharma organizations themselves, one would have expected the situation to be much different. Their stated business purpose – ‘Health for All’, does not seem to recognize: “Every patient deserves to get the medications they need at a cost they can afford,’ as AHIP reiterates. Whereas, “drug makers are gaming well-intentioned legislation to generate outsized profits from drugs intended to treat a small population of patients with rare diseases.” In this scenario, reaping a rich harvest with the orphan drug status seems to have become a new normal.

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.