The Case for Continued Public and Private Commitment to Rare Disease Research and Development

This is a paper written by a high school student with PV and was mentioned in the Spring 2009 Quarterly.

A rare disease is defined by the federal government as one that affects less than 200,000 people in the United States (NORD 1). The National Institutes of Health (NIH) recognizes about 6,000 distinct conditions as rare diseases (Murphy 12). These disorders affect more than 25 million people in the United States. In other words, approximately one in every ten people suffers from a rare disorder (NORD 1). Historically, the small numbers of patients suffering from individual rare diseases received limited medical support. For the past quarter century, however, the medical community and the federal government have worked together to provide these individuals with diagnostic care, medications and treatment, and financial support comparable to those with more common illnesses. In addition to serving the rare disease community, this public-private cooperation is even more significant because of the nature of rare diseases. According to Stephen C. Groft, director of the NIH Office of Rare Diseases (ORD), “the course that a rare disease takes often may represent an exaggerated form of a common disease pathway, and studying one helps scientists learn about the other” (U.S. FDA 1). The public and private commitment to the rare disease community and the issues facing it must continue because of the ultimate benefits for not only the 25 million Americans affected by rare diseases, but also for the millions of others nationwide affected by more common diseases.

Before the passage of rare disease laws in the United States, pharmaceutical companies did not develop medications for small groups of people because it was not profitable. Since no one wanted to “adopt” them, medications to treat rare disorders were labeled “orphans.” Orphans were either drugs or biologics developed for use in a rare disease or condition (U.S. FDA 1). A biologic is a product derived from a living organism that is used in the diagnosis or treatment of a disease. Examples of biologics include gene therapy, allergy shots, vaccines, and blood products. Since they are created from living organisms, manufacturing biologics requires extremely specialized techniques and controlled environments. In contrast, drugs are manufactured using chemicals, allowing them to be more easily controlled and mass-produced. Prior to production, however, the research and development costs to bring a new drug to market average more than $800 million; biologics cost even more (NORD 5). Because of this, pharmaceutical companies focused their resources on developing medications for major illnesses from which they could make large profits. This changed in 1983 when Congress passed a federal law called the Orphan Drug Act (ODA). The ODA provided financial incentives for companies to research and develop treatments targeting rare diseases, rewarding them with tax reductions and exclusive rights to the drugs they develop. The ODA has been very successful. Since 1983 “more than 200 new drugs and biological products for rare diseases have been brought to market” (U.S. FDA 2). In contrast, in the ten years prior to 1983, less than ten treatments for rare diseases were developed. Another way medications are awarded orphan status is when they are developed for another use, but are found to be effective in treating a rare disease. “To date over 1,400 existing drugs and biologics have been designated as orphan drugs” (U.S. FDA 2). As a result, treatments are available to people with rare diseases who once had no hope of survival. In addition, there have been cases where an orphan drug actually turned out to be very profitable, though this was never expected. For example, the drug Erythropoetin, commonly referred to as EPO, was initially developed for treating small numbers of kidney patients on dialysis. It turned out to be effective in treating the common condition of anemia, and is now the world’s best selling orphan with $8 billion in worldwide sales (NORD 11).

Despite the progress made since the ODA was passed, “the rare disorders community remains underserved and burdened in a variety of ways” (NORD 31). Three main issues face patients with orphan diseases: delays in diagnosis and treatment, lack of reliable information, and the high cost of medication.

A major issue facing patients with rare diseases is that physicians do not often see or understand the symptoms of these illnesses.

Many rare disorders lacked even something as basic as an identifying name, and if there were scientists focused on finding causes or cures, they usually worked in isolation and with little or no funding unless they happened to have a wealthy patron with a personal interest in finding answers. (Murphy 15)

Although the symptoms can be similar to more common diseases, those of rare diseases are usually more severe, last longer, and are seen in combination with other seemingly unrelated problems. When their symptoms do not resolve, patients are sent from one specialist to another, enduring sometimes painful and invasive testing procedures. Many times they are given multiple medications for inaccurate diagnoses. “For 1/3 of people with a rare disease, getting an accurate diagnosis can take 1-5 years” (Rados 1). Compounding this problem is the limited number of doctors trained to treat rare diseases. For some, there is only a handful of doctors in the world who have experience with them. Thus, a patient who is very sick may have to travel long distances to receive adequate care. This places both financial and physical burdens on an already ill patient. If more doctors understood the connections between rare diseases and common ones, patients would be better served.

Once a patient is diagnosed as having a rare disease, the next step is determining a treatment path. Rare diseases are serious chronic diseases, and are often life-threatening. For many rare diseases, there is no cure, but treatment of the symptoms can help (Rados 2). Genetic research over the last fifteen years has revealed that most rare diseases have a genetic component (Murphy 25). They are inherited, or caused by genetic defect or mutation. As scientists become better at discovering the genetic causes of rare diseases, finding effective treatments becomes more likely. To encourage the development of new treatments for rare diseases, the FDA established the Office of Orphans Product Development (OOPD). One of the OOPD’s roles is to coordinate and fund clinical trials to assess the effectiveness of experimental treatments on patients. One type of trial evaluates off-label use of existing drugs. “Off-label means a drug is used to treat a condition for which it is not specifically approved by the FDA” (Appleby 1). Use of an existing drug to treat a rare disease bypasses the time and expense for research and development, benefiting both the patient and the manufacturer. For example, one drug used to treat a rare autoimmune disease called pemphigus vulgaris is called Cell Cept. This drug was developed as an anti-rejection agent for kidney transplant patients. Through clinical trials, researchers found that it successfully suppressed the immune systems of pemphigus patients with low risk of side effects. “Bringing together limited numbers of patients who wish to participate in clinical trials and drug developers who are testing new treatments” (Murphy 21) is one of the most serious challenges facing the rare disease community. And yet clinical trials are the only way effective new treatments and potential cures will be discovered.

A more personal and psychological issue facing patients is that they are often scared, confused, and anxious to obtain understandable information about their disease and treatment. Although each rare disease has relatively few patients, “together they and their families constitute a lobbying force 25 million strong” (Murphy 19). In 1983, the National Organization for Rare Diseases (NORD) was formed to bring these people together.

NORD’s premise is that because only small numbers of patients suffer from any one rare disease, no single disease-specific voluntary health organization can assemble the resources required to effectively address, on a national and international bases, the common issues which face rare disease patients. (NORD 1)

This organization provides educational materials to physicians and patients for more than 1,100 rare disorders, thus helping to ease patient anxiety. NORD also brings together the various parties interested in clinical trials, and presents at medical conferences in the United States and around the world so more doctors are educated about the rare disease community. One of NORD’s most important accomplishments was its role in creating the Office of Rare Diseases (ORD) at the NIH in 1995. Prior to this, there was no coordination among the twelve separate NIH organizations studying rare diseases, resulting in duplication of effort or no effort at all. ORD now brings together the work of many disciplines, sharing ideas and discoveries with other groups in the NIH, even those studying common diseases. The result is better medical knowledge at lower overall cost.

A final challenge is that many of the treatments for rare diseases are extremely expensive. “In the last 5 years specialty drug prices rose 40% per year while non specialty drug costs rose 15% annually” (NORD 1).  The result is that some patients pay as much as $200,000 per year for their medications. Without adequate health insurance, some miracle drugs are priced out of reach for patients. Prohibitive health insurance policies include denial of pre-existing conditions, exclusion of specific diseases, overly long waiting periods, and lifetime dollar limit caps on benefits. “Under rules issued last year by the Bush administration for the Medicare Part D, so called off label prescriptions written by doctors for their patients can be denied by insurers” (Appleby 1). To address this issue,

NORD administers patient assistance programs for pharmaceutical and biotech companies; these are programs of last resort and are designed to assist individuals who cannot afford the often extraordinary costs of prescribed medications. (Murphy 21)

Prior to the 1980s, rare diseases went virtually unnoticed except among the relatively small population of individuals and their families who were directly affected (Murphy 15).  Since that time, and especially since the ODA was passed and NORD was formed in 1983, patients suffering from rare diseases gained both legal status and an advocate to help with getting properly diagnosed and treated, obtaining educational materials to learn about their condition, and receiving financial assistance if necessary. Looking toward the future, the ODA “will most likely see much more activity” (Murphy 25). Genetic research continues to shed light on the origin of rare diseases, and new rare diseases are discovered every year.
Scientists have discovered that genetic ‘snips’ are responsible for an estimated five thousand hereditary diseases, including a good share of orphan diseases. With more extensive research, still other relatively common diseases, including many cancers, may also turn out to have genetic ‘misspellings’ as a causative factor. (Murphy 24)

But all this knowledge comes at a price. Continuing to unravel the genetic code is the key to curing almost all rare and many common diseases in the future. It will take the combined efforts of brilliant researchers, advocacy groups like NORD, pharmaceutical companies, the medical community, and the federal government working together to reach this goal.

Works Cited
Appleby, Julie. “Off Label Drugs Denied to Patients in Medicare D.” USA Today 2 Aug. 2007.
Murphy, Wendy B. Orphan Diseases : New Hope for Rare Medical Conditions. New York: Twenty-First Century Books, 2002.
NORD. “The NORD and the Experiences of the Rare Disorder Community.” NORD. 9 Oct. 2008 .
Rados, Carol. “Orphan Products- Hope for People with Rare Diseases.” Medline Plus. FDA Consumer Magazine, 2003. 1-7.
US Food and Drug Administration. “Frequently Asked Questions.” FDA Office of Orphan Product Development. 9 Oct. 2008 .


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