Rare Diseases and Orphan Drugs: Status, Reimbursement, and Management

San Diego—There are approximately 7000 diseases that are categorized as rare, but only 5% of those have approved treatments. The 1984 amendment to the Orphan Drug Act of 1983 (ODA) defined a rare disease as one that affects 200,000 people in the United States. Existing laws such as the ODA and the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA) were designed to promote research into treatments for rare diseases.

At an AMCP Contemporary Issues session titled Current Status, Reimbursement, and Management Strategies for Orphan Drugs, Rare and Ultra Rare Diseases, Matt Cheung, PhD, FCSHP, FASHP, provided attendees with the latest data on this disease category. Dr. Cheung is principal, Advanced Rx Consulting, LLC, and adjunct professor of pharmacy practice, University of the Pacific, Thomas J. Long School of Pharmacy & Health Sciences.

Dr. Cheung began his presentation by noting that the definition of a rare disease outlined in the 1984 ODA amendment varies in other countries, and that most countries do not have official definitions for rare diseases.

The causes of rare diseases are diverse and, in many cases, unknown, Dr. Cheung continued. Approximately 80% of rare diseases are genetically based, due to inheritance of mutation of genes; other conditions are acquired through infection, toxic exposures, or radiation, and 50% of the conditions affect infants and children. Rare diseases are serious, life altering, life threatening, or fatal.

Dr. Cheung continued his presentation with an overview of orphan drugs. He said that the ODA established the Office of Orphan Product Development (OOPD) as part of the FDA. The OOPD reviews and approves the designation of orphan drug status for medications and therapies.

The orphan drug designation provides certain financial incentives, including a 7-year marketing exclusivity, a 50% tax credit for clinical investigation expenses, exemption of Prescription Drug User Fee Act fees, the possibility of an accelerated approval, and the ability to apply for FDA Orphan Drug Development grants.

The principal criteria for a designation of orphan drug are: (1) the drug is designed to treat a rare disease or condition or a plausible subset; (2) if the prevalence of the disease is >200,000 patients, sales of the product are not expected to cover the development costs; (3) there is medical plausibility for benefit; and (4) there is plausibility of superiority over an existing drug or therapy.

From 1973 to 1983, there were only 10 orphan drugs approved. From 1983 through 2012, there have been 2730 drugs given orphan drug status; of those, 421 have been approved, according to data presented by Dr. Cheung. Of the orphan drugs available in 2012, 36% are oncology drugs, 13% neurology, 7% hematology, 6% pulmonary, 5% metabolism, 5% ophthalmology, and 28% other.

In 2012, the FDA’s Center for Drug Evaluation and Research granted 39 new molecular entity/new biologic entity approvals; of those, 13 were for rare diseases and the remaining 26 were for common diseases.

Dr. Cheung said that major hurdles remain in the development of orphan drugs, including little change in government funding (only 11.4% of the National Institutes of Health budget is devoted to rare diseases and orphan drugs) and uncertainties in the orphan drug approval pathway. In addition, only 16% of rare diseases have a dedicated advocacy foundation working to support research and development on drugs and therapies to treat the conditions.

There are things managed care organizations (MCOs) can do to help with the treatment of rare diseases and development of orphan drugs, Dr. Cheung said. He called for MCOs to be educated about rare diseases/orphan drugs, add staffing for disease management programs for rare diseases, and engage with other stakeholders by supporting research activities and developing treatment guidelines and reimbursement policies for rare diseases.

The presentation ended with an overview of the role of pharmacists in the treatment and management of rare diseases. Dr. Cheung said pharmacists should strive to understand the unique characteristics of patients with rare diseases, including their associated disabilities and special needs, and provide comprehensive monitoring of therapies and interventions to identify potential drug interactions between orphan drugs, non-orphan drugs, over-the-counter medications, and supplements.

In summary, Dr. Cheung said the major drivers for rare disease/orphan drug development include escalating public awareness of the conditions, advancements in genomic/molecular/biologic technology, financial incentives from the ODA, and recent regulatory changes and market successes.