Pediatric Orphan Drug Indications: 2010-2018.

BACKGROUND: Orphan drug development is crucial for children, who are disproportionately affected by rare diseases. Data are lacking on the number, nature, and benefit of recently approved pediatric orphan indications. METHODS: We classified the 402 orphan indications the US Food and Drug Administration approved between 2010 and 2018 as "pediatric" if they were approved for children only or targeted pediatric diseases. We determined the number of unique diseases targeted by pediatric orphan indications and calculated the proportion that were for (1) novel drugs, (2) non-novel drugs approved to treat ≥1 common disease, and (3) non-novel drugs approved only to treat rare diseases. Among pediatric orphan indications eligible for US Food and Drug Administration breakthrough designation (granted to drugs potentially representing major therapeutic advances), we calculated the proportion receiving this designation. RESULTS: Of the 402 orphan indications, 136 (33.8%) were pediatric. These 136 indications targeted 87 unique diseases; 21 diseases were targeted by ≥1 indication. Of the 136 pediatric orphan indications, 60 (44.1%) were for novel drugs, 45 (33.1%) were for non-novel drugs approved to treat ≥1 common disease, and 31 (22.8%) were for non-novel drugs approved only to treat rare diseases. Among 97 indications eligible for breakthrough designation, 20 (20.6%) received this designation. CONCLUSIONS: Recent orphan drug development has increased the availability of treatments for pediatric rare diseases. Most pediatric orphan indications expanded use of existing drugs, and many targeted the same disease. Some indications may represent breakthroughs, but substantial unmet need for treatments remains for most pediatric rare diseases.

Achieving orphan designation for placental insufficiency: annual incidence estimations in Europe.

OBJECTIVE: To determine whether a novel therapy for placental insufficiency could achieve orphan drug status by estimating the annual incidence of placental insufficiency, defined as an estimated fetal weight below the 10th centile in the presence of abnormal umbilical artery Doppler velocimetry, per 10 000 European Union (EU) population as part of an application for European Medicines Agency (EMA) orphan designation. DESIGN: Incidence estimation based on literature review and published national and EU statistics. SETTING AND POPULATION: European Union. METHODS: Data were drawn from published literature, including national and international guidelines, international consensus statements, cohort studies and randomised controlled trials, and published national and EU statistics, including birth rates and stillbirth rates. Rare disease databases were also searched. RESULTS: The proportion of affected pregnancies was estimated as 3.17% (95% CI 2.93-3.43%), using a weighted average of the results from two cohort studies. Using birth rates from 2012 and adjusting for a pregnancy loss rate of 1/100 gave an estimated annual incidence of 3.33 per 10 000 EU population (95% CI 3.07-3.60 per 10 000 EU population). This fell below the EMA threshold of 5 per 10 000 EU population. CONCLUSIONS: Maternal vascular endothelial growth factor gene therapy for placental insufficiency was granted EMA orphan status in 2015 after we demonstrated that it is a rare, life-threatening or chronically debilitating and currently untreatable disease. Developers of other potential obstetric therapies should consider applying for orphan designation, which provides financial and regulatory benefits. TWEETABLE ABSTRACT: Placental insufficiency meets the European Medicines Agency requirements for orphan disease designation.

Orphan Drugs and Their Impact on Pharmaceutical Development.

High levels of productivity, with an increasing number of approvals for new molecular entities (NMEs) by the FDA during the past decade, have coincided with the emergence of innovative drugs for treatments of rare diseases that have utilized the FDA orphan drug program. Since 2000, NMEs with orphan designation encompass a significant portion of approved drugs and constitute about 80% of the approved drugs that have established novel human genome-encoded products in recent years. Biological approvals are also expanding, with 40% of the approved biological agents having orphan designation. This trend illustrates a pivot within the pharmaceutical industry: from research programs that focus on canonical blockbuster indications and targets, towards the establishment of new treatments for rare and difficult to treat diseases.

Do investors value the FDA orphan drug designation?

BACKGROUND: The Orphan Drug Act is an important piece of legislation that uses financial incentives to encourage the development of drugs that treat rare diseases. This analysis studies the effects of a portion of the Orphan Drug Act, the orphan drug designation. Specifically, it studies the value that investors place on the orphan drug designation, by investigating how investors react to companies' announcing that their product has received the designation. RESULTS: The results, on average, show that the stock price of a company increases by 3.36% after the announcement of the designation, increasing the value of the company. The results are more pronounced for oncology drugs, and drugs being developed by the smallest companies. CONCLUSION: The orphan designation appears to be successful at generating positive value for companies, as seen by the positive and significant average increases in stock price.

Rare Disease Terminology and Definitions-A Systematic Global Review: Report of the ISPOR Rare Disease Special Interest Group.

BACKGROUND: At present, there is no universal definition of rare disease. OBJECTIVE: To provide an overview of rare disease definitions currently used globally. METHODS: We systematically searched for definitions related to rare disease from organizations in 32 international jurisdictions. Descriptive statistics of definitions were generated and prevalence thresholds were calculated. RESULTS: We identified 296 definitions from 1109 organizations. The terms "rare disease(s)" and "orphan drug(s)" were used most frequently (38% and 27% of the definitions, respectively). Qualitative descriptors such as "life-threatening" were used infrequently. A prevalence threshold was specified in at least one definition in 88% of the jurisdictions. The average prevalence threshold across organizations within individual jurisdictions ranged from 5 to 76 cases/100,000 people. Most jurisdictions (66%) had an average prevalence threshold between 40 and 50 cases/100,000 people, with a global average of 40 cases/100,000 people. Prevalence thresholds used by different organizations within individual jurisdictions varied substantially. Across jurisdictions, umbrella patient organizations had the highest (most liberal) average prevalence threshold (47 cases/100,000 people), whereas private payers had the lowest threshold (18 cases/100,000 people). CONCLUSIONS: Despite variation in the terminology and prevalence thresholds used to define rare diseases among different jurisdictions and organizations, the terms "rare disease" and "orphan drug" are used most widely and the average prevalence threshold is between 40 and 50 cases/100,000 people. These findings highlight the existing diversity among definitions of rare diseases, but suggest that any attempts to harmonize rare disease definitions should focus on standardizing objective criteria such as prevalence thresholds and avoid qualitative descriptors.

Unintended effects of orphan product designation for rare neurological diseases.

Since the introduction of the Orphan Drug Act in 1983, designed to promote development of treatments for rare diseases, at least 378 orphan drugs have been approved. Incentives include financial support, tax credits, and perhaps most importantly, extended market exclusivity. These incentives have encouraged industry interest and accelerated research on rare diseases, allowing patients with orphan diseases access to treatments. However, extended market exclusivity has been associated with unacceptably high drug costs, both for newly developed drugs and for drugs that were previously widely available. We suggest that a paradoxical effect of orphan product exclusivity can be reduced patient access to existing drugs. In addition, the costs of each new drug are arguably unsustainable for patients and for the American health care system. Of all the specialties, neurology has the third highest number of orphan product designations, and neurological diseases account for at least one-fifth of rare diseases. Citing the use of tetrabenazine for chorea in Huntington disease, adrenocorticotropic hormone for infantile spasms, and enzyme replacement therapy with alglucosidase alpha for Pompe disease, we highlight these paradoxical effects.

Necesidades en las enfermedades raras durante la edad pediátrica / Needs in rare diseases during paediatric age

Las enfermedades raras plantean una serie de retos a los afectados y sus familias: el diagnóstico, afrontar los síntomas, la información sobre la enfermedad, obtención de atención sanitaria adecuada, disponibilidad de fármacos, discapacidad e impacto emocional. Los niños con enfermedades raras constituyen un grupo poblacional muy importante desde el punto de vista de los servicios sanitarios y sociales, y las familias deben proporcionar cuidados durante largo tiempo a estos niños enfermos. La repercusión de las enfermedades raras en los niños es de gran alcance, extendiéndose más allá de ellos mismos, a todas las personas de su entorno. Son múltiples las facetas de la vida afectadas, incluyendo las relaciones familiares y sociales, el bienestar económico o las actividades cotidianas. La evaluación de las necesidades en las enfermedades raras es una fase crítica para proporcionar una atención sanitaria de alta calidad y conseguir la satisfacción del enfermo y su familia. Los hallazgos de diferentes estudios han puesto de manifiesto que las personas con enfermedades raras tienen necesidades médicas y sociales. Las necesidades sociales están adquiriendo una gran relevancia en los países desarrollados, en los que los servicios sanitarios, aún con limitaciones, tienen mayor disponibilidad que los servicios sociales. Por consiguiente, parece necesario que los servicios sanitarios y sociales para las personas con enfermedades raras deben mejorarse para abordar las necesidades de los pacientes y proporcionar mejor apoyo a las familias. En este sentido, sigue siendo necesario disponer de instrumentos validados con buenas propiedades psicométricas para valorar la calidad de la asistencia en función delas necesidades de los pacientes y sus familias (AU)

All rare diseases present a common set of challenges to the sufferers and their families: diagnosis,dealing with symptoms, health information, obtaining helpful medical care, availability of medications,disability and emotional impact. Children with rare disorders are an important population from health care services, and social services perspectives, and families are providing long-term care for these chronically ill children. The impact of rare disorders in children is far reaching, extending beyond the child to all those with whom he/she has contact. Multiple facets of life are affected including social an family relationships,economical well-being and activities of daily living. The assessment of needs for rare disorders treatment is a critical step in providing high quality care and achieving patients’ and families’ satisfaction. Findings from different studies show that people with rare diseases have medical and social needs. Social needs are becoming more relevant in developed countries where health care services, even with limitations, have greater availability than social services. Furthermore, it seems that health care and social services for persons with rare diseases need to be improved to address the patients’ needs and to provide better support to families. Validated tools with good psychometric properties are still needed to assess quality of care on the basis of patients and family needs (AU)

Radiopharmaceuticals as orphan drugs.

Rare diseases and conditions are defined as diseases or conditions that affect less than 200,000 individuals in the United States. Because of the limited population suffering from any given rare disorder, there is little economic motivation for the development of drug products for its diagnosis or treatment. Also, frequently these rare diseases are misdiagnosed or undiagnosed due to a lack of familiarity with their symptoms and course. Thus, these rare disorders are commonly referred to as orphan diseases or conditions. To address this problem, legislation has been enacted that provides for incentives for the development of drug products for rare diseases or conditions (i.e., orphan drug products). Nuclear medicine scientists can take advantage of these incentives in the development of orphan radiopharmaceuticals for the treatment or diagnosis of rare diseases or conditions. Nuclear medicine physicians should know where information on orphan diseases and orphan radiopharmaceuticals can be obtained to maximize the care of their patients.