There exist an estimated 7,000 rare diseases - some with unpronounceable names like Angiolympoid Hyperplasia with Eosinphillia, Mucopolysaccharidosis, and Waldenström’s Macroglobulinemia. Otherwise known as orphan diseases, they are among a group ofmedical conditions that affect 200,000 or fewer people in the United States.
Highly recognizable orphan diseases - like Amyotrophic Lateral Sclerosis (commonly known as ALS or Lou Gehrig's disease) and Cystic Fibrosis each have a prevalence (total number of cases at any given time) of approximately 30,000 Americans. Others, an estimated 5,600 - approximately 80 percent of all orphan diseases - are categorized as ultra orphan diseases, each affecting no more than 6,000 individuals. Some are so rare that as few as 150 patients have been identified as in the case of Niemann Pick Type C, a fatal condition often referred to as “childhood Alzheimer’s.”Another, Severe Congenital Protein C Deficiency, is a life-threatening clotting disorder that has been diagnosed in fewer than 20 Americans.
In this nation of more than 310 million people, one in ten suffers from a rare disease. And of that 30 million, 50 percent are children, about 30 percent of whom die before reaching their fifth birthday according to the National Institutes of Health (NIH) and The National Organization for Rare Disorders (NORD).
Troubling statistics aside, these specially-designated disorders present significant, ongoing and sometimes devastating challenges - medically and financially - for patients and their families. Many of the diseases - 80 percent of which are genetic in origin - lack effective treatment, do not attract public attention because of their rarity and run the gamut from fatal, life-threatening, chronic, disabling and disruptive. And thus begins a domino affect – theabsence of awareness and support resulting in inadequate financial assistance for the protracted, costly process that leads to drug and product development. This is an unacceptable situation and as an essential component of improving our healthcare system, orphan drug innovation needs to be addressed as a priority.
Since the 1983 implementation of the Orphan Drug Act (created to stimulate the development of drugs for rare diseases by providing private industry with financial incentives and market exclusivity - a seven year monopoly – to develop drugs and medical devices) a number of public policy efforts have been established including The Office of Orphan Products Development, The Rare Diseases Act, The Rare Diseases Orphan Product Development Act, The Office of Rare Diseases and the Therapeutics for Rare and Neglected Diseases Program, the latter two out of the National Institutes of Health (NIH).
While to a varying extent all of the aforementioned have been effective, none, singularly or in collaboration, have made for a comprehensive fix. Despite inducements including multimillion dollars in government research funds, progress in the rare disease community continues to be challenging and insufficient.
To complicate matters, there is the perception of a hierarchy within the orphan disease community. Resources are limited in this high-cost, low-volume marketplace (low patient numbers), so research and funding are targeted towards the patient population with the greatest prevalence and/or highest visibility such as those that are endorsed by celebrities. As a result, those within the ultra-rare disease population have the additional burden of self-advocacy at an even greater level than those in the more populous orphan disease sector.
Another controversial issue is the belief that the cost of bringing orphan drugs to market (reportedly lower than that in the general drug market) is unfairly inflated and passed along to the patients. Dr. Pedro Cuatrecasas, a former pharmaceutical executive and current adjunct professor of Pharmacology and Medicine at the University of CA, San Diego, contends that “some companies now apparently feel that desperate patients (and society) will pay whatever is charged.” As an example, he sites Cerezyme, used to treat Gaucher Disease at the annual cost of $200,000 for children and $600,000 for adults. The ability to commercially exploit patients by high pricing and profits has “stimulated spectacular success in discovery research and rapid development demonstrating, cynically, the current technical capacity of major companies to apply modern science to many diseases,” he adds.
In the absence of treatment for a specific disease, compassionate drug use – providing experimental drugs and therapies (prior to final FDA approval) for the critically ill who have no other treatment options and are not a part of a clinical trial – is an alternative that needs to be more accessible. Currently, sanction of this under-utilized and commonly unrecognized provision is tightly controlled, time-consuming and allowed only under limited, special circumstances. Moreover, insurers are not mandated to cover the cost of off-label use and experimental medications and devices. Yet the critical need for an increased frequency of compassionate drug use is underscored by the disheartening fact that as of last fall, NORD reported treatments for only 200 of the rare 7,000 diseases.
Another option that must be widely utilized is the FDA’s recently launched Rare Disease Repurposing Database which identifies 236 drugs deemed “promising” for orphan disease treatment (although not approved for marketing) but have secured FDA approval for another medical condition. The hope is that “repurposing” these drugs for a rare disease will provide an expedited, less expensive process for the manufacturer and benefit patients by getting the drugs to market quicker.
In a depressed economy and an environment of healthcare reform - spending cutbacks, exclusions and increasing regulatory requirements - continued, significant financial incentives coupled with much-needed public support are essential for continued research and development in this highly-specialized market. Protocols, strategies and goals need to be reassessed and updated because in fact, rare diseases represent and remain a relatively neglected area of unmet medical need. Financial supplementation from the private sector needs to be encouraged along with innovative, aggressive efforts to tackle the multiple and complex needs.
February 28 marked the fourth International Rare Disease Day during which the United States and patient organizations from 53 other nations sought to draw attention to rare diseases and seek equality for the millions who are affected by them. This year’s slogan “rare but equal” expressed the ultimate goal of raising awareness to finance and combat thousands of rare diseases that affect millions of Americans - many of whom are without resources, support or hope.
-Gayle S. Fixler has a Bachelor of Science degree in journalism from Arizona State University, is a Washington, DC freelance writer and a regular contributor to Reflections.
