Pamela Koerner, PharmD

Brittany Albert, PharmD, and Marissa Puc, PharmD contributed to the research and writing of this white paper. 

Part 1 of this 3-part series explores the details of how changes in United States federal policy and advances in scientific research led to the dawn of medical breakthroughs for rare disorders. Part 2 will describe how rare pharmacy has emerged distinctly from specialty pharmacy to address the unique needs of patients, biopharma, providers, and payers. The series will conclude by highlighting the proposition that patients with rare and devastating disorders require and deserve the high acuity of care and service that only an accredited rare pharmacy can deliver. 

Background on Rare Disease Pharmacy Development 

The orphan drug market has become a significant focus of specialty pharmacy as an unprecedented number of medications for rare and devastating diseases enter the US marketplace. In response, legislative changes have significantly enhanced the development of new treatment options, changing the lives of the patients with these diseases. While these agents are transforming lives, they come at a very high cost and with a multitude of challenges for patients and the health care system. Specialty pharmacies have continued to evolve to meet the needs of this challenging population and other stakeholders. 

Although an estimated 7000 rare diseases exist, only about 500 have FDA-approved treatment options, providing only 7% of patients suffering from rare diseases with access to pharmaceutical therapy.

 The number of patients with an unmet need is staggering and illustrates a gap in medical care. In response to changes in legislation, manufacturers have begun pursuing this once-underexplored area of drug development, creating a significant shift in focus toward rare disease treatment. The United States passed the Orphan Drug Act in 1983, effectively incentivizing drug discovery for rare diseases. In this country, orphan drugs are defined as treatments for diseases that affect 200,000 or fewer individuals within the United States.

 The National Organization for Rare Disorders estimates that approximately 10% of Americans are afflicted with a rare disease.3 This number is roughly the size of the population in the United States with diabetes. It is estimated that more than half of the people afflicted with a rare disease are children, and that 80% of rare diseases are genetic in origin.

As new orphan drugs enter the US marketplace at an accelerated rate, patients’ lives are being transformed by these unique therapies. To date, 849 orphan drug approvals have been granted by the FDA.4 Of the 59 drugs approved in 2018, 34 were designated with orphan status.5 By 2024, orphan drugs are expected to account for more than a third of total research and development pipeline sales.6 Currently, 4409 drugs with orphan designations are awaiting review and potential approval.

Reviewing legislation leading to its development helps to better understand the emergence of the orphan drug market. In 1983, the Orphan Drug Act passed, inspiring the treatment advances we continue to see today. This act, which amended the Food, Drug, and Cosmetic Act enacted in 1938, was intended to stimulate the development of medications for rare diseases by providing incentives to manufacturers to devote resources for advancing research for conditions with limited patient populations.

 These incentives include grants for clinical research support, tax credits for research costs, and 7 years of market exclusivity for an approved drug.

The Pediatric Rare Disease Voucher Program, developed as part of the 2012 FDA Safety and Innovation Act, further encouraged the development of drugs for rare pediatric diseases.

 This program catalyzed development of new therapies for orphan and rare pediatric diseases by awarding both priority FDA review to applications that meet certain criteria, as well as a voucher for a future priority review upon successful approval.

 These vouchers can have a monetary value to manufacturers and they can be sold or transferred, as was the case when United Therapeutics sold their voucher to AbbVie in 2015 for $350 million, benefiting both manufacturers and their specific needs at the time.

 Originally set to expire in 2016, the voucher program was extended through September 30, 2020, resulting in continued pediatric orphan drug development.

In addition, the FDA Office of Orphan Products Development administers 3 extramural grant programs: the Orphan Products Clinical Trials Grants Program, which provides funding for clinical research that tests the safety and efficacy of drugs, biologics, medical devices, and medical foods in rare diseases or conditions; the Natural History Grants Program, which supports studies that advance rare disease medical products development through characterization of the natural history of rare diseases and conditions; and the Pediatric Device Consortia Grants Program, which provides funding to develop nonprofit consortia to facilitate pediatric medical device development.

Due to the number of orphan drug designations awaiting approval, in 2017 the FDA announced the Orphan Drug Modernization Plan to facilitate review.

 The ultimate intent was to bring more orphan drugs to market that can not only treat diseases, but provide life-changing opportunities to people suffering from rare and devastating conditions. Blood, central nervous system, and respiratory disorders were the leading orphan drug therapeutic areas in 2018 and are projected to remain so in 2024, accounting for more than 50% of the nononcology orphan drug market.

The aforementioned pieces of legislation provided economic incentives for manufacturers to make large investments in research for diseases affecting small, often pediatric patient populations. This has resulted in the development of treatment for orphan conditions such as spinal muscular atrophy, Duchenne muscular dystrophy, hypophosphatasia, and central precocious puberty. 

The orphan drug market has become a significant development and commercialization focus for the biopharma industry, and an unprecedented number of medications for rare and devastating disease are entering the US marketplace. While these agents are transforming patients’ lives, the medications come at a very high cost and with a multitude of challenges for the patient and health care system. As the number of drug approvals has increased, there has also been an increase in the number of specialty pharmacies. The number of accredited specialty pharmacies has nearly doubled in recent years, from 381 in 2015 to 729 in 2017.

The specialty pharmacy industry has evolved since its inception in the 1980s. Specialty pharmacy began slowly with the launch of alglucerase injection (Ceredase) for Gaucher disease.

 In its early years, specialty pharmacy focused on catastrophic illnesses, including HIV, AIDS, hepatitis C, hemophilia, and organ transplant treatments.10 Specialty pharmacies continued to expand services to patients with multiple sclerosis, rheumatoid arthritis, and other conditions, for which high-cost therapies were coming to the market and changing patient care. The growth of treatment options, ease of medication management, development of evidence-based clinical guidelines, and expert professionals with comprehensive knowledge in targeted treatment areas for these chronic conditions have shifted the efforts of specialty pharmacy to more complex, limited resource conditions such as rare diseases. 

Specialty pharmacy management strives to improve patient outcomes by providing high-touch services for complicated medication regimens. Working with the prescriber, specialty teams assist in patients’ medication journeys by improving adherence, counseling on adverse effects to prevent drug-related problems, and assisting with financial and psychosocial needs. While the goals of specialty pharmacy have remained the same over time, market consolidation and product commoditization have altered the composition and focus of specialty pharmacies. Now, with the strong flow of new and complex rare and ultra-rare (European Union definition: fewer than 1 person in 50,000) disease therapies receiving FDA approval, specialty pharmacy is playing a renewed, pivotal role in removing treatment barriers and enhancing patient care. 

Of all the patients suffering from rare diseases, only a very few currently have access to an approved pharmaceutical therapy. In response to changes in legislation, manufacturers are now pursuing this once-underexplored area of drug development, creating a significant shift in focus to rare disease treatment. These market changes caused specialty pharmacy to reevaluate the standard of current practice in an effort to meet the needs of patients. 

The rare disease landscape has many unique challenges in the patient care process. The rarity of disease states coupled with novel medication mechanisms and high costs lead to complexities in accessing treatment and optimizing outcomes. Located at the center of the medication use process, a new type of specialty pharmacy focused exclusively on rare diseases (rare pharmacy) can play a leading role in providing optimized care for patients while tackling challenges, easing burdens, and addressing all stakeholder needs. 

Part 2 of the series will provide insights into the rare pharmacy market and the challenges for manufacturers, providers, payers, pharmacies, and patients. 

, is chairman and CEO, PANTHERx Rare, and associate dean for business innovation, University of Pittsburgh School of Pharmacy.

, is associate professor, School of Pharmacy, and director, Giant Eagle Center for Pharmacy Practice, Duquesne University, Pittsburgh.

, is senior vice president and head of pharmacy, PANTHERx Rare. 

NORD Issues New Rare Disease Day Rallying Cry: Show your stripes. National Organization for Rare Diseases website. 

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National Organization for Rare Disease Fact Sheet. National Organization for Rare Diseases website  

https://rarediseases.org/wp-content/uploads/2014/11/NORD-fact-sheet-cover.png

Orphan Drug Designations and Approvals. FDA website. 

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EvaluatePharma Orphan Drug Report 2019. EvaluatePharma website. https://info.evaluate.com/rs/607-YGS-364/images/EvaluatePharma%20Orphan%20Drug%20Report%202019.pdf?mkt_tok=eyJpIjoiWWpVMk1UVmtNRFpqT0dFeiIsInQiOiIrcmZ3QjNwamZWWVwvZ1ZkcU5XS2E3Rk5oNXA5MXZJVUVCRitMQXpQd0sxMGJPU0JhdGRWbVJQQkZrc0xZNDNPSXRNM09wMGh2OEFXNXFNN1wvb1plT April 2019. Accessed April 13, 2020. 

Developing Products for Rare Disease and Conditions. U S Food and Drug Administration, 2020. Web 17 April 2020

Vanscoy J, Gebhard D, Ogurchak J, et al. Specialty pharmacy today: improving the lives of patients with rare diseases through orphan drug management. 

https://www.pharmacytimes.com/publications/specialty-pharmacy-times/2017/september-2017/specialty-pharmacy-today-improving-the-lives-of-patients-with-rare-diseases-through-orphan-drug-management

Rare Pediatric Disease Priority Review Vouchers Guidance for Industry. U.S Food & Drug Administration, July 2019. Web. 13 April 2020. https://www.fda.gov/media/90014/download.

Vanscoy J. The emergence of specialty pharmacy. 

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Exclusive: A record number of specialty pharmacies now have accreditation. 

. April 2018. Web 13 April 2020. https://www.drugchannels.net/2018/04/exclusive-record-number-of-specialty.html.

Articles

The rarity of disease states coupled with novel medication mechanisms and high costs lead to complexities in accessing treatment and optimizing outcomes.