Profiles of Rare Disease Heroes
Champion for ODA and founder of National Organization for Rare Disorders
Abbey Meyers pioneered the development and passage of the 1983 Orphan Drug Act, catalyzed by her experience as a parent of a child with Tourette syndrome who lost access to an experimental orphan drug. Through Abbey’s efforts, the voices of those with rare diseases were amplified throughout industry and government. Abbey continued to educate and advocate for rare diseases through her work as the founder of the National Organization for Rare Disorders (NORD).
Representing 1st approved orphan designated drug and patient advocacy
Hemin was the first orphan designated drug to receive marketing approval in 1983. It is used to relieve recurrent attacks of acute intermittent porphyria (AIP). In AIP, an important part of hemoglobin called heme is not made properly, causing varying symptoms with the most common being severe abdominal pain. Desiree Lyon was 17 years old when she had her first attack and suffered undiagnosed for over a decade. In 1982 she was given experimental hemin at the National Institutes of Health, tremendously improving her quality of life. At the time, Desiree cofounded the American Porphyria Foundation and spoke in front of Congress to support the Orphan Drug Act. She continues to be an active rare disease advocate today.
Representing Parent advocacy for newborn screening and medical foods
Jana Monaco has been an advocate for the rare disease community since her son Stephen suffered severe brain damage at age 3 because of undiagnosed isovaleric acidemia (IVA). IVA is a metabolic disorder that can lead to episodes of illness called metabolic crisis, which may be avoided by restricting protein in the diet and the use of medical foods. Jana’s daughter Caroline was diagnosed before birth, thus avoiding a metabolic crisis by proper medical management. Like many rare disease patients and their families, through her experiences Jana has become a champion for rare disease issues such as newborn screening, medical foods insurance coverage, and neurodevelopmental disabilities awareness.
Representing Clinician/product developers and advocates; Developed the artificial rib humanitarian use device
Dr. Robert Campbell developed the Vertical Expandable Prosthetic Titanium Rib (VEPTR), saving the lives of hundreds of children. VEPTR is an expandable titanium artificial rib that treats a life-threatening condition called thoracic insufficiency syndrome, in which there is not adequate room in the chest cavity for organ growth. The VEPTR was first approved by the FDA in 2004 as a Humanitarian Use Device. Dr. Campbell has also worked tirelessly to support advocacy efforts for the development of pediatric medical devices.
Advancing rare disease information, collaboration, and research
The National Institutes of Health (NIH) Office of Rare Diseases Research (ORDR) led by Dr. Steve Groft was established in 1993 with the goals of stimulating and coordinating research on rare diseases. The ORDR, now part of the National Center for Advancing Translational Sciences, supports research and responds to the needs of the global rare disease community by leveraging NIH resources and fostering collaboration across NIH, among academic and industry stakeholders, and with patient advocacy groups through programs such as the Genetic and Rare Diseases Information Center and the Rare Diseases Clinical Research Network.
Author and cosponsors of the Orphan Drug Act (ODA)
Representative Henry Waxman was the principal author of the original 1983 Orphan Drug Act (ODA). Senator Orrin Hatch was a co-sponsor and champion of the ODA. The ODA provided the first meaningful incentives to sponsors to develop needed medical products for the estimated 25 million Americans with rare diseases, defined under the ODA as diseases or conditions that affect fewer than 200,000 people in the United States. Fewer than 10 products supported by industry for rare diseases came to market between 1973 and 1983. Since its passage over 400 products for rare diseases have been approved.
Organization, education, support, research, advocacy, and action
The years surrounding the passage of the Orphan Drug Act spurred a national awareness of the challenges that people with rare diseases face and a commitment, not only to find treatments, but to come together as a community. The bedrock of these efforts are the many rare disease advocacy groups who work tirelessly every day to put voices and faces to their diseases in providing support to families in their daily challenges, educating the community, and supporting research into their diseases
Developing products in the spirit of the ODA
The discovery, development, and clinical testing of products whether for rare or common diseases can be a long and expensive process. In the spirit of the Orphan Drug Act, since its passage, many contributors such as pharmaceutical companies, angel investors, foundations, venture capitalists, and academic/research organizations have come together to advance the development of over 400 products for rare diseases.
Advancing orphan products through orphan designations, grants, and facilitation
FDA’s Office of Orphan Products Development (OOPD) was established in 1982. Its critical role in providing incentives for the development of products to prevent, diagnose, and treat rare diseases was spelled out in the 1983 Orphan Drug Act. Since then, OOPD has advanced rare disease research and product development, through its core programs – orphan drug designation, humanitarian use device designation, clinical research grants, pediatric device consortia, and an expanding outreach initiative. Dr. Marlene Haffner, OOPD Director for nearly two decades served as an international ambassador for FDA's orphan product development incentives.
Dr. Hal Dietz discovered fibrillin-1 as the underlying genetic cause of Marfan syndrome (MFS) in 1991. MFS is a potentially fatal connective tissue disorder, which leads to enlargement of the aorta. Dr. Dietz’s devotion to patients, both in the clinic and in the laboratory, has continued full force, and he has since helped to discover the genes underlying other conditions that cause aortic aneurysms, including Loeys-Dietz syndrome. In addition, his work has shown that the pathogenesis of MFS is more complex but at the same time more amenable to pharmacotherapy, leading to the first clinical trial in MFS.
Sharon Terry began her journey as a patient advocate setting out to accelerate research on pseudoxanthoma elasticum (PXE). PXE is a rare disorder which causes the skin, eyes, and other organs to become mineralized. Soon after her daughter and son were diagnosed, Sharon and her husband organized a worldwide association of individuals affected by PXE and their families, collected DNA samples, and helped coordinate scientists in an effort to pull together the resources necessary to find the gene, create a diagnostic, validate biomarkers, conduct clinical trials and accelerate interventions . Sharon has continued to spur collaborative efforts in genetic disease translational research and services as President and CEO of Genetic Alliance by empowering others to become full participants and reclaim their health.
The Undiagnosed Diseases Program (UDP) uses the unique combination of medical expertise and special resources at the National Institutes of Health (NIH) to evaluate patients with medical conditions that have long eluded diagnosis. The UDP, led by Dr. William Gahl, is a trans-NIH initiative that responds to a critical unmet need with clinical expertise and genomic technologies. The program has gained novel insights about diseases and therapeutic strategies.
Dr. Nancy Wexler is the President of the Hereditary Disease Foundation, started by her father Milton Wexler in 1968. She has devoted her scientific career to research on Huntington disease (HD), a hereditary fatal brain disorder, for which she herself is at risk. Since 1979, Dr. Wexler has led a research study of the world's largest family with HD, leading to the identification of the HD gene and development of a presymptomatic test. Her work has advanced research on HD and assisted in identifying other disease genes, including those for familial Alzheimer disease, amyotrophic lateral sclerosis, neurofibromatosis and dwarfism. Dr. Wexler is also active in public policy for rare disease, and has held numerous public policy positions, and received many honors and awards.
Ashley Appell is one of over 25 million Americans living with a rare disease. Ashley was born with albinism, which leads to diminished pigment in the skin, hair, and eyes and a visual impairment. When she started to walk her mother became concerned about continuous bruising, and Ashley was found to have a bleeding problem due to abnormal platelets. She was diagnosed with Hermansky Pudlak syndrome (HPS), a form of albinism which includes other health problems such as colitis and pulmonary fibrosis. Ashley has been part of an HPS research study since childhood. As a young adult she takes every opportunity to educate and advocate for HPS and rare diseases, including displaying her singing skills at events and taking part in the documentary Rare. Ashley’s mother, Donna Appell is cofounder of the HPS Network.
Ronald Bartek cofounded the Friedreich’s Ataxia (FA) Research Alliance (FARA) to support families and find a cure for FA after his son Keith was diagnosed at age 11 with FA. FA is a rare, genetic, neurodegenerative, multisystem disorder. After Keith’s passing at age 24, Ron and FARA continue their commitment to advancing a research alliance to support basic and translational research, drug development, clinical trials, and collaborations to treat FA.
Tiffany House was diagnosed with Pompe disease at age 11 after a childhood of multiple respiratory illness and the slow onset of muscle weakness. Pompe disease is a metabolic disorder that ultimately leads to the deterioration of the muscles such as those of the limbs and heart. At age 16, Tiffany began participating in clinical trials that lead to the approval of the orphan biologic product, Myozyme®, for the treatment of Pompe disease. Tiffany has advanced the Patient Representative Program at FDA by facilitating increased communication with the patient community in the drug development process.
FDA’s Center for Drug Evaluation and Research (CDER) Rare Diseases Program was established in 2010 to facilitate and support research, development, regulation, and approval of CDER’s drug and biologic products for the treatment of rare disorders. The Program has served to coordinate the development of CDER policy, procedures, and training for the review and approval of treatments for rare diseases and works collaboratively with external and internal rare disease stakeholders to support the sound scientific development of treatments for rare disorders.
Advances in personalized medicine can allow doctors to identify patients who will benefit the most from a particular drug. Kalydeco®, is such a medicine and was approved early in 2012 for the treatment of a rare subgroup of cystic fibrosis (CF) patients, those who have a G551D mutation in the CFTR gene. The drug received assistance for its clinical development through the FDA Orphan Drug Designation and Orphan Products Grants programs and other support. CF is a serious disorder which results in the formation of thick mucus that builds up in the lungs, digestive tract, and other parts of the body leading to severe respiratory and digestive problems, as well as other complications such as infections. Laura Cheevers and her sister Cate were in and out of the hospital frequently with infections and tired easily as young children, until they participated in and received Kalydeco in clinical trials. Laura and Cate are now recovering easily from colds and flourishing in dance class and soccer games.
Dr. Leslie Boyer has focused her scientific career on venomous bites and stings, which are often unrecognized public health issues. She began by developing public education programs that offer poison and toxin emergency treatment advice. In 2004 and 2005, with an FDA Orphan Product grant, she led a team that conducted the clinical studies leading to the marketing approval of the first scorpion antivenom—representing one of over 40 products developed through orphan grant sponsored research. She continues her commitment through the study of a treatment for coral snake bites.
Dr. Denise Ney, a researcher in nutritional sciences, follows over 160 patients with phenylketonuria (PKU). PKU is a genetic disorder caused by deficiency of an enzyme that converts the essential amino acid phenylalanine to tyrosine. To prevent brain damage and cognitive impairment those with PKU must follow a lifelong, low-phenylalanine diet through restriction of their diet and the use of a bitter tasting amino acid formula. Dr. Ney provides education on the importance of nutritional management of PKU, and under the auspices of the Orphan Grants program is conducting clinical studies to establish the acceptability and safety of unique foods made with whey protein for PKU.
Raising awareness about rare diseases and the need for medical products
In the early 1980’s Jack Klugman, star of the television series, “Quincy,” successfully raised public awareness about rare disease issues by highlighting them in two “Quincy” episodes. He even testified before Congress. Since that time, media has continued to spotlight rare diseases in television, such as “House” and “Mystery Diagnosis,” and in films, such as “The Elephant Man” and “Extraordinary Measures.”
FDA continues its long-standing commitment to rare diseases and developing diagnostics and therapeutics for those with unmet medical needs. The collective efforts of many individuals across the FDA have helped to bring over 400 rare disease products to the market ~approximately 1/3 of all new molecular entities a year. Through strong communication and collaboration across the rare disease community, FDA remains committed to strong regulatory science to maximize the contribution of and minimize the risk to patients who volunteer for clinical trials to advance products for rare disease patients.
The National Institutes of Health (NIH) Therapeutics for Rare and Neglected Diseases (TRND) program was established in 2009 as a unique program that assists drug discovery by bridging the gap that often exists between basic research discoveries and the testing of new drugs in humans. The work of TRND includes the optimization and preclinical testing of therapies to generate sufficient quality data to support successful first-in-human studies. TRND stimulates research collaborations among NIH and academic scientists, nonprofit organizations, and pharmaceutical and biotechnology companies to foster the successful commercialization of new treatments for rare and neglected diseases.
Finding treatments for rare disease is a worldwide challenge. The Orphan Drug Act spurred an international orphan drug movement, with the European Union, Japan, Australia, and others since developing orphan drug legislation to encourage the development of treatments for rare diseases. Today the FDA continues to work collaboratively with international government agencies and advocacy groups on behalf of rare diseases.
Dr. Pearl O’Rourke began her career as a pediatric critical care physician. She was active in clinical research and served many years as an Institutional Review Board member. After completing a Robert Wood Johnson Health Policy fellowship she worked in the Office of Science Policy at the National Institutes of Health on issues such as privacy, gene therapy, embryonic stem cells, and genetic discrimination. She works now to support the regulatory and ethical oversight of human research and the responsible conduct of research, and has been a strong advocate on behalf of rare diseases.
Dr. Jouni Uitto is internationally recognized for his research in skin disorders. The overall goal of his research has been to elucidate the mechanisms that lead to defects in collagen, elastin, and the basement membrane of the skin that would explain the clinical symptoms of disorders such as epidermolysis bullosa and pseudoxanthoma elasticum. His work in refining the pathology and genetic classification of many rare skin disorders has had a significant impact on the care and counseling of patients as well as for the development of novel treatment strategies.
George Harris Carter has had personal experience with the affects of sickle cell disease (SCD), leading him to be a patient advocate for over thirty years. SCD is an inherited blood disorder where normal round shaped red blood cells change to a sickled shape, ultimately blocking the flow of blood and oxygen to body parts and tissues leading to extreme pain. Lack of oxygen flow can also damage muscles, bones and internal organs and lead to other serious medical problems. George has dedicated himself to educating the public about SCD and providing patients with support by leading local the statewide Sickle Cell organization in his home state of Virginia. He has also been a strong advocate for drug development and clinical trials, serving as FDA Office of Special Health Issues (OSHI) Patient Representative for SCD.
Clinical-Healthcare professional involved in providing direct patient care to a patient population with rare diseases
Physicians, nurses, genetic counselors, and other healthcare professionals are essential to the rare disease community in providing support to families on a daily basis. Many also work to educate the community and through their diagnosis and treatment efforts have helped to support the ever increasing knowledge about rare diseases.
The EXCOR® Pediatric Ventricular Assist Device (VAD) was designated a Humanitarian Use Device (HUD), studied in clinical trials supported by the Orphan Products Grants Program, and approved in 2011 under a Humanitarian Device Exemption (HDE). The device is specifically designed for children with heart failure until they can receive a heart transplant.
Josie was a healthy 7 year old girl until October 2010, when she fell ill and was diagnosed with myocarditis. Myocarditis is an inflammation of the heart muscle, which causes the heart to become thick and weak. Josie’s heart was failing and she needed a heart transplant. As her condition worsened quickly she underwent surgery to receive the VAD, which supported her successfully through the 11 month long wait for her heart transplant- leading her parents to become strong advocates for the device and organ transplantation.
Dr. Howell is not only a pediatrician but an advocate for patients, and a champion of furthering the early detection and treatment of many metabolic and congenital disorders. As Chairman of the Secretary's Advisory Committee on Hereditary Disorders in Newborns and Children (SACHDNC), he has been instrumental in establishing and expanding newborn screening programs across the nation. His work has fostered communication within the community and has spurred new technologies and treatments related to newborn screening.