Richard Faris, PhD, RPh

 of this 3-part series explored the details of how changes in US federal policy and advances in scientific research have led to the dawn of medical breakthroughs for rare disorders. 

 of the series examined how rare pharmacy has emerged distinctly from specialty pharmacy to address the unique needs of patients, biopharma, providers, and payers. The series concludes looking at the proposition that patients with rare and devastating disorders require and deserve a higher acuity of care and service that only an accredited rare pharmacy can deliver.

Located at the center of the medication use process, a rare disease—focused pharmacy can play a leading role in providing optimized care for patients while tackling challenges, easing burdens, and addressing all stakeholder needs. With a specialized, multifunctional team that coordinates care, a rare disease–focused pharmacy, or more succinctly, a rare pharmacy, can contribute to improved quality of life for people living with chronic and devastating diseases. A rare pharmacy can simplify the complex process of getting orphan medicines from innovators to the people who need them most by removing barriers to access therapy and patient care.

A rare pharmacy must possess clinical expertise, robust disease-state management programs, mechanisms to optimize compliance, adverse drug effect counseling, reporting capabilities, prior authorization support, and co-pay card support, and focused educational capabilities for patients, physicians, and payers. Data management, customization, and sharing capabilities are also critical, as many orphan medications are approved based on a single clinical trial in a small patient population and require ongoing data analysis.

It is fundamental for a specialty pharmacy to provide patients with a more specialized experience than would be expected from a traditional pharmacy. A pure rare pharmacy accurately and precisely delivers consistent quality care to patients with rare and devastating diseases without the distraction of the diverse responsibilities encumbered with larger populations (traditional specialty pharmacy). In the case of rare pharmacy, the patient experience needs to be specialized to the level of individualization, and high-frequency patient engagement must be the norm. Ongoing, personalized communication is crucial to this experience, as patients and their families deal with the burden of a rare and devastating disease state. The support network for such diseases, though available, are not as readily accessible as those for conditions with more ubiquitous presences, and a rare pharmacy must be the conduit for this support. Interactions with the patient—such as discussions regarding medication adverse effects (AEs), the impact of the disease, nutrition, and addressing financial barriers through coordinated co-pay assistance&mdash;can, when conducted properly, reduce stress and make days more manageable for people dealing with these debilitating diseases. In many cases, these therapeutic agents will not cure their diseases; however, when part of a carefully managed plan, they will still provide patients with a priceless improvement in quality of life.

What Makes a Rare Pharmacy Different Than a Specialty Pharmacy? 

Rare pharmacies are adapting to the emerging orphan drug market and providing new solutions to address the challenges facing the health care system. The chasm separating specialty and rare pharmacy ultimately stems from a rare pharmacy’s need to comprehend a patient’s entire journey, which begins well in advance of medication dispensing. A rare pharmacy must establish individualized relationships with patients and understand the entire journey, including onset of a patient’s first symptom, difficulties of diagnosis, and day-to-day challenges. Because patient populations are so small and available data are much more limited, each experience can add depth to a patient’s profile and, if understood and used correctly, can allow a rare pharmacy to deliver more effective care. By understanding the depth and variety of possible patient journeys for a specific rare disease state, a rare pharmacy can establish a framework and develop and execute a standard of care.

Furthermore, a rare pharmacy recognizes that no two patient journeys are the same. In collaboration with industry partners, rare pharmacies customize solutions built around a product and personalize the support services delivered to the patients based on their individual needs. As a standard, each rare program is tailored to maximize the benefits of an individual therapy and then adapted to the symptoms, lifestyle, and preferences of each patient. Every patient should feel that they have the undivided attention of their rare pharmacy care team and that each team member is invested in their health.

Directed Clinical Program Development and Patient Support 

Patients living with a rare and devastating condition often require additional support services and a pharmacy that can go beyond drug dispensing. The clinical and patient engagement programs extend to understanding the patient journey and what they have experienced to get to this point in treatment. The program design must integrate clinical information with an understanding of that patient’s health beliefs and what motivates them. This design requires new thinking and an informatics system that can respond to queues throughout the care process. The rare pharmacy’s ability to leverage specialized teams and technology to onboard new medications and ensure patients receive uncompromised care will differentiate them from other specialty pharmacies. Dedicated efforts during predrug launch, implementation, and postlaunch ensure successful execution.

Single Point of Contact and Targeted Education 

To appropriately care for patients with rare diseases, specialized, cross-functional, disease state—focused teams must be the model. These teams should be comprised of, but not be limited to, program managers, pharmacists, nurses, clinical advisors, patient care representatives, insurance specialists, and data analytics professionals. Every member of these teams must serve as a patient advocate, assisting patients as they navigate their treatments and progress through their journey. Team size, composition, and the roles/responsibilities should be customized based on the specific needs and characteristics of the patient population being served.

As part of the customized program development, a rare pharmacy must implement a robust training program on the disease state, patient journey, and therapeutic options. Product and AE management training and operational protocols are essential for teams to provide optimal patient care.

It is imperative that patients are informed about, and engaged in, every step of their prescription journey. Initial communications and introductions to pharmacy services are critical parts of developing the relationship between a pharmacy and its patients. These conversations allow patients to articulate their specific goals and the pharmacy team to curate an understanding of their treatment histories, providing targeted counseling and outlining medication expectations. In instances of complex dosing or titration schedules, patients must be strategically contacted to review new dosing, ensure appropriate administration, aid in AE management, and discuss adherence.

Adverse Drug Event Reporting and Management 

Due to the small number of patients with any one rare disease, novel therapeutic agents are approved and enter the market based on results from limited clinical trial data. Many of these medications are approved on an accelerated track, and the true clinical risks and benefits are still being vetted and established. Postmarket surveillance is crucial to ensure patient safety in the rare disease market. Specialty pharmacies are very familiar with AE reporting, but rare pharmacies need to be innovative to enhance the standard process and give insights into real-world therapy outcomes on a patient-by-patient basis.

Rare pharmacies need to have comprehensive reporting structures and communication platforms that allow for direct interfacing and real-time updating. Based on the individual product needs, reporting can be conducted in various ways to keep manufacturers updated and to remain compliant with FDA requirements. The analysis of these data is essential, as it allows the pharmacy to provide updated educational programs to patients and health care providers, resulting in increased safety. In addition to the data collection platform, the use of dedicated pharmacists who are experts in specific diseases and treatments allows for consistent reporting of adverse effects and uniform medication education.

Ability to Alleviate Financial Obstacles 

If a patient does not receive a prescribed medication, there can be no positive impact on the patient’s disease state and health outcome. Obtaining the necessary medications is the only way to alleviate their symptoms, but high costs and complicated prior authorization (PA) processes often delay the process.

Rare pharmacy must involve personnel who understand and work through financial barriers and payer hurdles to obtain therapy for the patient. This may include PAs and appeals process support. Understanding payer policies and the information required for approval can reduce rejections and the time to get a patient on therapy.

Even when payer coverage criteria are cleared, the patient’s financial responsibility may cause them to walk away from receiving the needed medication. The rare pharmacy must have processes in place to direct patients in need to either co-pay assistance programs or foundation support.

A dedicated insurance resolution specialist is essential to guaranteeing that all options, including third-party payment assistance programs, foundation support, and free goods or bridge programs, are investigated for each patient. All stakeholders recognize the important role a rare medication has in a patient’s life and appreciate that cost alone should not be a barrier to seeking the only treatment that may be available.

Quickly and effectively managing referrals is vital to improving patient outcomes. Prescriptions may be obtained through hubs, electronic prescribing platforms, phone, or fax. While referral processing is standardized across the industry, a rare pharmacy can differentiate itself by ensuring effective communication with the health care team from the start of the process. Resources need to be dedicated to understanding the payer landscape, and previous experience with complex coverage criteria is essential. Prioritizing interprofessional collaboration with the entire health care team allows for a seamless patient journey and optimal patient health outcomes.

Rare pharmacies should also have capabilities to serve as a hub, as is often the case when a manufacturer has chosen to distribute its rare therapy through an exclusive pharmacy arrangement. By serving as both the central point for referrals and the pharmacy, the rare pharmacy can reduce the time to process referrals and give a complete picture to the manufacturer. Additionally, this may reduce confusion for the patients and prescribers, as only one entity is calling and coordinating the prescription journey. The rare pharmacy would operate the spectrum of services utilizing specialized teams, strong communication platforms, and high-touch patient and health care provider engagement.

Due to their unusually high costs, new-to-market novel and targeted rare therapies typically have payer requirements that must be met prior to coverage. A survey of payers reported that 97% of orphan drugs require PA, 55% are placed on a specialty tier, and 27% required the addition of step edits. In addition, 25% of payers may require an increase in cost sharing with patients.

A rare pharmacy uses expert clinicians and auxiliary internal processes to request and obtain the required clinical information mandated by the payer. The rare pharmacy’s high level of disease knowledge, medication expertise, and health care provider integration allow for proactive systematic collection of information that aids in the processing of PAs. This expertise ensures that PAs and appeals reach their determination points as complete and as quickly as possible.

Expert Fulfilment, Distribution, and Supply Chain Support 

The ability to coordinate mail-order shipping, temperature-sensitive supply chain requirements, and inventory management is essential to rare pharmacies. Due to the high costs of therapies and unique circumstances of associated rare disease states, fulfilment and distribution errors could be financially damaging to a company and prevent a patient from obtaining life-saving medications according to their care plan.

Exclusive distribution networks allow for a consistent patient experience, which is ideal for small patient populations. Rare medications are not suited to the high-volume, standardized patient management approaches seen in other areas of pharmacy, including traditional specialty pharmacy. Exclusive distribution networks offer benefits for patients with rare diseases because the distributing pharmacy has the expertise to provide extensive monitoring and customized therapy support.

Exclusive distribution networks allow patient management to be tailored to specific patient types and impacted health care providers. In addition, these partnerships can adhere to strict shipping, tracking, and storage requirements and handle complicated logistics scenarios, such as cold chain management.

Ultimately, a rare pharmacy will use myriad resources to ensure the timely delivery of a safe and effective product.

Systematic and Customizable Data Reporting Capabilities 

Reporting data to manufacturer partners is a standard practice in the specialty pharmacy industry. Rare pharmacy differentiates itself by providing data-reporting elements that are fully customizable based on each medication’s distinct needs to capture all facets of the patient journey. Additionally, data are reported to manufacturers and payers at agreed-upon frequencies based on individual partnerships. The small populations associated with rare medication dispensing demand highly specialized data reporting and analytical capabilities so that data can be reviewed on a patient-by-patient basis to identify trends and insights. It is also critical for a rare pharmacy to have the capability to track patients who transition from a clinical trial to the expanded-access environment.

In addition to data reporting, a rare pharmacy monitors key performance indicators and utilizes dashboard technology to benchmark data, track progress, and ensure operational excellence at the therapy level. Similar to the disease state—specific team structure, data analytics teams focus on individual drug products and customize their processes and outputs accordingly. Focused analysis allows for continuous process improvement; real-time metrics and data-driven program changes result in enhanced patient experiences.

Respected Accreditations and Specialized Distinctions 

Manufacturers, providers, and payers agree that specialty pharmacies must have high standards and strict requirements to ensure excellent patient care. One mechanism of ensuring care quality at specialty pharmacies is the accreditation process. In a recent payer survey, 50% said they require their specialty pharmacies to have at least 2 accreditations, and all payers require URAC accreditation specifically.

 Specialty pharmacies most commonly hold 2 accreditations: URAC and the Accreditation Commission for Health Care (ACHC).

With the emergence of rare pharmacies, industry stakeholders have recognized the importance of creating accreditations associated specifically with rare pharmacy that require even higher standards and stricter requirements than specialty pharmacy accreditations. In 2019, the establishment of the ACHC Distinction in Rare Diseases and Orphan Drugs differentiated rare disease—focused pharmacies from traditional specialty pharmacies.

This year, URAC also introduced a rare disease—focused designation. This offers existing URAC-accredited specialty pharmacies the opportunity to further distinguish themselves from other specialty pharmacies to demonstrate competence in rare pharmacy.

The rare drug industry continues to grow exponentially. Orphan drug sales are projected to account for more than one-third of research-and-development pipeline sales by 2024.

 With this expected growth, specialty pharmacies need to focus and develop enhanced service capabilities to become better suited to provide care to patients with rare diseases. Advances and innovations in drug development and genetics have already transitioned rare pharmacy into a new era of precision medications that present new and more complex challenges. Payers, manufacturers, and specialty pharmacies are combining their efforts to establish a model for payment, distribution, and administration. The emergence of value-based models and care-coordination strategies will promote the future of precision-therapy advancements.

 Rare pharmacies are positioned to be a leading force in the next era of patient care.

It is exceedingly important that specialty pharmacy continues to grow and adapt to the changing health care environment. The medications and patients in the rare and orphan category bring unique challenges to pharmacies, and the industry needs to be prepared.

Patients with rare diseases still face considerable obstacles to care, including management of their complex medication therapy, drug access, and high cost of treatment. Rare pharmacies are in a pivotal position to provide reliable, high-touch care with flexibility and nimbleness that can make a difference in the lives of patients, caregivers, and every member of the health care system.

, is Chairman and CEO of PANTHERx Rare and associate dean for business innovation at the University of Pittsburgh School of Pharmacy in Pennsylvania.

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

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

, for their assistance in the research and writing of this white paper. 

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

September 2017. Accessed April 13, 2020. 

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

Grogg AL. Payer trends impacting the orphan drug market. Amerisource Bergen. April 18, 2017. Accessed October 12, 2020. 

https://docplayer.net/50090131-Payer-trends-impacting-the-orphan-drug-market.html

CSI Specialty Group. 2019 state of specialty pharmacy report. Accessed April 13, 2020. 

https://academynet.com/sites/default/files/csi2019spreport.pdf

Fein AJ. Exclusive: a record number of specialty pharmacies now have accreditation. 

. April 10 2018. Accessed October 12, 2020. 

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

ACHC Launches First Distinction in Rare Diseases and Orphan Drugs. News release. Accreditation Commission for Health Care. October 1, 2019. Accessed April 15, 2020. 

https://www.achc.org/pdf/Distinction_Rare_Diseases_Orphan_Drugs_PR.pdf

Evaluate. EvaluatePharma orphan drug report 2019. April 25, 2019. Accessed April 13, 2020. 

https://www.evaluate.com/thought-leadership/pharma/evaluatepharma-orphan-drug-report-2019

CVS Health. Gene therapy: keeping costs from negating its unprecedented potential. 2020. Accessed October 14, 2020. 

https://payorsolutions.cvshealth.com/sites/default/files/cvs-health-payor-solutions-gene-therapy-keeping-costs-from-negating-its-unprecedented-potential-white-paper-january-2020.pdf

Articles

The series concludes looking at the proposition that patients with rare and devastating disorders require and deserve a higher acuity of care and service that only an accredited rare pharmacy can deliver. 

Rare Pharmacy Emerges From Specialty, Part 3

 of this 3-part series, published in last month’s 

™, explored how changes in US federal policy and advances in scientific research have led to the dawn of medical breakthroughs for rare disorders. Part 2 describes how rare pharmacy has emerged distinctly from specialty pharmacy to address the unique needs of patients, biopharma, providers, and payers.

In the rare disease landscape, the patient care process presents many unique challenges. The rarity of the disease state coupled with novel medication mechanisms and high costs leads to complexities in accessing treatment and optimizing outcomes. To fully understand and appropriately manage this market, manufacturers, providers, payers, pharmacies, and patients need to recognize the challenges and identify the mechanisms to overcome them.

The complexity of developing a rare medication is recognized and acknowledged by industry stakeholders. This is in part due to the physiology of many rare diseases, which present unique hurdles for scientists, as inherently small patient populations make recruiting for and conducting clinical studies difficult; indeed, a rare disease is defined as one that afflicts fewer than 200,000 patients in the United States.

 As such, the process of understanding the disease and developing an effective and tolerable medication for patients is often a lengthy one. The Pharmaceutical Research and Manufacturers of America indicates that developing orphan medications takes on average 2.3 years or longer.

 In addition to lengthy research and development processes, manufacturers encounter barriers when bringing a new treatment to market, including establishing a distribution network, navigating payer controls, and reviewing potential financial barriers for patients.

Although recent scientific developments and technological improvements are aimed at optimizing orphan medication development, a manufacturer still faces the challenges of identifying the best fit in choosing their preferred distribution channel, such as a specialty pharmacy.

 Data show that many manufacturers use limited distribution models and select their pharmacy partners based on quality, provision of high-touch patient care, and capacity to navigate payer complexities to access medications.

 A continual challenge to manufacturers, choosing the right launch strategy to distribute their product is a crucial component of their drug development and commercialization process and must include consideration for the need for hub services, data aggregators, distributors, and the number of specialty pharmacies that will dispense the medication.

 A solid foundation with the specialty pharmacy services in product distribution and patient engagement is necessary to achieve success in the marketplace.

In a survey about the greatest challenges manufacturers faced from 2017 to 2018, 33% cited payer controls and payer-created access restrictions as major hurdles in the development process.

 In addition, manufacturers recognize the expense of developing orphan medications and the out-of-pocket cost for patients and have sought to create access mechanisms for patients who do not gave traditional payment options.

 Through foundation support and co-pay assistance programs, manufacturers are striving to improve access to these life-altering medications. Between 2014 and 2018, the mean orphan drug cost per patient was approximately 4.5 times that of a nonorphan drug.

 Interestingly, though, that price differential has decreased by almost 50% in the past 4 years.

Despite the barriers that manufacturers face when launching a new medication, offering a life-changing therapy for a rare disease where none previously existed is the ultimate victory. Improvements in the patient’s quality of life and health outcomes continue to drive future development opportunities and challenge manufacturers to keep filling gaps in the rare disease space.

Payers are responsible for determining how to cover the cost of medications and control associated spend across patient populations. Patients with rare diseases are challenging to payers because small patient populations can consume larger-than-proportional percentages of total costs. Specialty prescriptions account for only approximately 2% of prescriptions but represent nearly 50% of total pharmacy expenditure.

 Payers review new medications and determine coverage criteria before they commit to reimbursement for the drug. These coverage determinations may place barriers between the prescribing physician’s decision-making and the patient who needs life-changing therapy.

Because medications for rare disease can be extremely costly, appropriate utilization is critical. As such, payers implement criteria to ensure appropriate utilization of the medications. Survey data show that when asked to identify some of their biggest challenges with specialty distribution, payers pointed to pricing, communication, and reporting.

 They also reported a need for consistency in pharmaceutical care, data sharing, and focus on patient outcomes.

A growing challenge for payers is the continued management of specialty drug spend as more orphan drugs come to market. With more technologies and medicines for rare disease reaching the final stages of development, payers are working to establish innovative payment models. These models need to allow appropriate access to these medications, including cell and gene therapies, while mitigating the financial impact on the health plan and individual employer groups. As the health care industry changes, new payment models are expected to follow.

Anxiety and fear of the unknown can affect not only patients with a rare disease but their families and caregivers as well. Approximately 50% of rare diseases affect children, and in these cases, parents and families must cope with difficult choices,

 and some 30% of patients with a rare disease die from their condition before age 5.7 As such, a great urgency exists to diagnose rare diseases and treat patients living with them, and the health care community must consider the impact on patients, families, and their support systems. The community and regulatory bodies recognize the importance of supporting research and building a community around rare diseases. In 2020, the FDA held a public meeting to observe Rare Disease Day and allow stakeholders to discuss issues for drug product development for rare conditions.

Unfortunately, the road to diagnosis and proper treatment is often difficult for patients and their families. The process can be lengthy and frustrating as patients and their families attempt to understand the disease, find an experienced physician, and seek treatment, all while going about daily life and trying to manage challenging symptoms. Through patient advocacy groups, patient assistance programs, and support services, the rare disease health care industry is making advances in providing optimal care and improving medication access, ensuring that the patient remains the focal point. Many patients who had difficulty receiving an accurate diagnosis or appropriate resources are now mentoring and supporting other members with new diagnoses in the rare disease community. Having gone throughthe challenges when the industry was less developed, the community was smaller, and less was known about rare disease, many community veterans know how hard the process was to navigate alone and want to make it easier for others. As such, rare disease communities have become an essential part of the patient’s care network.

Organizations such as the National Organization for Rare Diseases, Global Genes, and RareConnect have made patient advocacy their missions, providing support, information, and a network of health care professionals for those afflicted with a rare disease.

 The platforms for communication and information exchange among these organizations supplement rare disease organization sites focused on specific conditions. The dispensing specialty pharmacy also plays a critical role in providing continuous, reliable access to information on these resources for patients and their families.

In addition to finding support and educational resources after a rare diagnosis, patients also face challenges with diagnosis and treatment. The process of receiving an accurate diagnosis and finding a rare disease specialist is often fraught with delays and setbacks and can take years. Rare disease organization sites assist by compiling center-of-excellence locations and providing specialist listings of providers who are most knowledgeable about a specific rare disease. These resources save patients time and money while helping alleviate their frustrations and providing answers. Although many rare diseases have historically been misdiagnosed, the health care community is improving education among professionals and developing tools for identifying the rarity of the disease and niche prescribing practices, allowing for more accurate and timelier diagnoses.

Compounding the barriers associated with seeking treatment for a rare diagnosis are delays in medication access due to payer coverage criteria. From the time a medication enters the market, patients and pharmacies work continuously to seek insurance approvals and ensure timely medication delivery. This process begins with the specialty pharmacy network selected to dispense the medication, and it works through the payer requirements together with prescribers and patients. The specialty pharmacy will look for co-pay and foundation support to help cover out-of-pocket costs when needed.

Innovations at the manufacturer, provider, and pharmacy levels are crucial to enhancing patient care. The many stakeholders in the rare pharmacy industry strive to understand each part of the patient journey and provide the best services to assist patients in all aspects of their treatment.

Of the FDA-approved medications for rare diseases, many are considered first in class, containing a novel mechanism of action designed for a very specific patient population. These products often have complex dosing regimens, unique adverse effect profiles, complicated prior authorization processes, and high out-of-pocket costs. Additionally, providers often do not have the resources to efficiently manage the unique, extended needs of these patients.

A common challenge for providers is difficulty in diagnosis. A reported 40% of patients with a rare disease receive a misdiagnosis at least once.

 An example of a commonly misdiagnosed rare disease is primary periodic paralysis. The principal clinical manifestation of the disease is episodic muscle weakness and, in some circumstances, corresponding abnormal potassium levels. These patients often receive a misdiagnosis of hypokalemia and are treated with potassium supplements, as primary periodic paralysis is present in only 4000 to 5000 patients in the United States and hypokalemia is much more common.

 This is but 1 example of how easily rare disease symptoms can reflect those of a more common disease state, leading providers down a path of exploring all possible diagnoses through trial and error.

Furthermore, providers must also have the confidence to prescribe and manage new-to-market medications. Unlike other medications, orphan products are supported solely by the clinical trial data of very controlled, small patient populations. These medications require high-touch management, near-constant monitoring, and pharmacy and physician collaboration. Providers need health care partners that not only provide necessary support for their patients but also assist the provider and their staff by imparting their unique knowledge of the drug and the disease state in question, managing the complexities of the medication, and collaborating to support medication acquisition for their patients.

In response to rapid advances in medications and the complexity of the disease states being treated, specialty pharmacies have adapted to expand their offerings and meet the needs of the changing market. The main challenges facing pharmacies dispensing medications for rare diseases are patient access to the medications and the patient experience. Centered on empathy and understanding, a superior patient experience is dependent on the pharmacy’s in-depth understanding of the patient journey, proper training, and continuous education. Often, individualized management of patients with a rare disease can translate into better outcomes. Specialty pharmacies should strive for continual improvement in their care models, focusing on the customization needed for each medication as well as data collection and reporting of program results. The focus of the industry should be on facets such as adherence, persistence, financial assistance, and the achievement of personal patient goals, which both independently and collectively optimize the patient journey.

As pharmacies enter the market for rare diseases, it is vital that they have the structure and technology to assist every patient taking these medications regardless of where they are in their journey. Programs need to have specialized teams that use program-specific technologies to guide them through the care process and to collect and analyze data.

Pharmacies that want to succeed in the rare disease space need to develop and implement programs that are different from what is currently used for other specialty drugs.

The rare disease spectrum is challenging for various stakeholders, including the manufacturer, the provider, the payer, pharmacies, and patients. The manufacturer has unique hurdles throughout the drug development, distribution, and marketing process. It is also tasked with making therapies affordable so that patients can benefit from advances. Payers need to work in concert with other members of the health care team to ensure appropriate utilization of these unique medications while mitigating the financial impact. Concurrently, providers also need support to navigate the rare disease space as they prescribe these complex, new-to-market therapies that require high-touch management and significant monitoring.

Patients are the most important part of this journey and are burdened with significant challenges, ranging from receiving an accurate diagnosis, locating support, and finding educational resources on their disease and medications. Adding to those barriers are concern over cost, delays in therapy secondary to insurance approvals, and medication delivery.

Located at the center of the medication use process, a new type of specialty pharmacy focused exclusively on rare diseases—rare pharmacy&mdash;can play a leading role in providing optimized care for patients while tackling challenges, easing burdens, and addressing all stakeholder needs. With a specialized, multifunctional team that coordinates care, a rare disease—focused pharmacy can improve the quality of life of patients living with chronic and devastating diseases. 

Part 3 of the series will highlight the proposition that patients with rare and devastating disorders require and deserve a higher quality of care and service that only an accredited rare pharmacy can deliver. 

, 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; and 

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

, contributed to the research and writing of this white paper.

Orphan Drug Act - relevant excerpts. FDA. Updated March 9, 2018. Accessed July 16, 2020. https://www.fda.gov/industry/designating-orphan-product-drugs-and-biological-products/orphan-drug-act-relevant-excerpts 

Strone G. ICYMI: orphan drug development brings unique challenges. Pharmaceutical Research and Manufacturers of America. May 21, 2018. Accessed July 16, 2020. 

https://catalyst.phrma.org/icymi-orphan-drug-development-brings-unique-challenges

CSI Specialty Group. 2019 state of specialty pharmacy report. The Academy. Accessed July 16, 2020. 

EvaluatePharma orphan drug report 2019. EvaluatePharma. April 25, 2019. Accessed July 16, 2020. https://www.evaluate.com/thought-leadership/pharma/evaluatepharma-orphan-drug-report-2019

Reinke T. Specialty drug spend soars. Can formulary management bring it down to earth? 

. 2019;28(9):23,28-29. Accessed July 16, 2020. https://lsc-pagepro.mydigitalpublication.com/publication/?i=613323&article_id=3460619&view=articleBrowser&ver=html5

Medicine use and spending in the U.S.: a review of 2018 and outlook to 2023. IQVIA. May 9, 2019. Accessed July 16, 2020. https://www.iqvia.com/insights/the-iqvia-institute/reports/medicine-use-and-spending-in-the-us-a-review-of-2018-and-outlook-to-2023

The global challenge of  rare disease diagnosis: a policy briefing. Shire. January 2015. Accessed July 16, 2020. 

https://www.shire.com/~/media/shire/shireglobal/shirecom/pdffiles/patient/therapeutic%20areas/diagnosis/2015-feb-shire-rarediseaseday-globalchallenge.pd

For patients & families. National Organization for Rare Disorders. Accessed April 13, 2020. 

Who we are. Global Genes. Accessed April 13, 2020. 

About RareConnect. RareConnect. Accessed April 13, 2020. 

Primary periodic paralysis. Strongbridge Biopharma. February 2020. Accessed April 13, 2020. 

https://www.strongbridgebio.com/therapeutic-focus/primary-periodic-paralysis/

Challenges and impact of rare diseases are faced by pharmacy stakeholders.

Rare Pharmacy Emerges From Specialty, Part 2

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. 

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

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Orphan Drug Designations and Approvals. FDA website. 

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Reinke T. Specialty drug spend soars. Can formulary management bring it down to earth?, Sep 2019. 

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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

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.

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

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