Horizon scanning and drug expenditure for rare diseases: three-year predictive model in Italy 2025–2027

With support from patient associations, political frameworks for rare diseases have been established throughout the world albeit with varying definitions for rare diseases. In the USA, the National Organization for Rare Disorders was instrumental in passing the 1983 Orphan Drug Act and the 2002 Rare Disease Act, which includes medical devices and dietary products as orphan products. In 2011, the House passed bills supporting research for undiagnosed diseases and preserving regulatory fee exceptions for orphan drugs. In 2012, the Canadian government awarded five-year rare disease research grants. With advocacy from the Canadian Organization for Rare Disorders, Health Canada concluded consultations on an orphan drug regulatory framework. Several provinces have implemented orphan drug access programs and expanded newborn screening. In Argentina, the Geiser Foundation led advocacy resulting in the 2011 Rare Disease Law, obliging health and social systems to provide assistance. A central committee, including patients, will coordinate activities like neonatal screening and patient registries. In 2010, Colombia passed the Orphan Disease Law and hosted the 2nd National Forum of Orphan Diseases. In 2011, Peru passed legislation promoting treatment and a national strategy including diagnosis, surveillance, prevention, care, and rehabilitation. Through the 1972 Medical Care Program for Specific Diseases, Japan provides medical cost subsidy to patients affected by “56 rare and intractable diseases.” The 1993 Orphan Drug Law supports research and development. In 2008, Supporting Organizations for Patients with Rare Diseases was formed. Since 1991, Singapore’s Orphan Drugs Policy allows patients with life-threatening and severely debilitating diseases with no other treatment options to access approved drugs prescribed by their practitioner. The Taiwan Foundation for Rare Disorders helped secure the Rare Disease and Orphan Drugs Act in 2000. Diseases affecting fewer than 1 in 10,000 that are officially recognized are eligible for medical coverage. In Korea, the Orphan Drug Centre supplies medicines for diseases affecting fewer than 1 in 20,000. The Genetics and Rare Disease Centre supports national reference centres and research. In China, in 2011, medical professionals called for legislation to support healthcare, research, orphan drug development, and epidemiological studies for diseases affecting fewer than 1 in 10,000. Australia’s 1987 Orphan Drugs Policy makes available rare disease drugs, based on US regulatory information. In 2010, consultation for a national strategy was posted online. In 2012, Rare Voices Australia was formed.

Rare diseases are frequently life-threatening or chronically debilitating and the impact on the quality of life of affected patients and their family members is thus significant. However, drug development for these conditions has been limited by a lack of understanding of the underlying mechanisms of disease and the relative unavailability of subjects for clinical trials, as well as the prohibitive cost of investing in a novel pharmaceutical agent with poor market potential. Nevertheless, the introduction of Orphan Drug legislations has provided important incentives for the development of orphan drugs (i.e. drugs that have been abandoned or 'orphaned' by major drug companies). Moreover, recent studies on rare diseases, including inherited immunodeficiencies and metabolic disorders, have served not only to alleviate the plight of patients with rare diseases, but also yielded valuable information on biological processes of relevance for other, more common conditions. These lessons, along with the crucial importance of cooperation between academic institutions, pharmaceutical companies, patient advocacy groups and society in the elucidation of rare diseases, are highlighted in the present review.

European solidarity is changing the face of rare diseases

PHP30 The Bittersweet Success of Orphan Drugs

Objective This study aims to analyze the effect of the copayment reduction system on accessibility to orphan drugs (ODs) in South Korea. Methods Data on approval and reimbursement for drugs designated as ODs for the last 10 years (2012–2021) in South Korea were extracted. Among them, with 136 approved products as of 31 December 2022, the reimbursement rates and lead time to reimbursement between drugs for rare diseases (DRDs) and nondrugs for rare diseases (non-DRDs) were analyzed. The pricing and reimbursement (P&R) pathways between drugs for only rare diseases (DORDs) and drugs for rare and cancerous diseases (DRCDs) were compared. Results The reimbursement rates for DRDs and non-DRDs were 54.8% and 33.3%, respectively, and the lead time to reimbursement for DRDs and non-DRDs were 16.1 months and 31.2 months, respectively. The P&R pathways for DORDs and DRCDs were pharmacoeconomic evaluation waivers (21.7% and 52.6%), weighted average price (52.2% and 13.2%), and risk-sharing agreement (30.4% and 81.6%). Conclusion The copayment reduction system may act as a driver and also barrier for the reimbursement of ODs. To expand treatment accessibility to ODs, it is necessary to consistently grants benefits in all processes from OD designation to market access.

Evinacumab Approval Adds a New Option for Homozygous Familial Hypercholesterolemia With a Hefty Price Tag

February 28, 2013 marks the sixth international “Rare Disease Day”. On and around this day, hundreds of patient organizations from more than 60 countries and regions worldwide plan to host awareness campaigns in line with this year's theme, “Rare Disorders without Borders”. Public awareness of intractable and rare diseases has heightened in recent decades. Much progress has also been made worldwide, such as specific legislation to encourage discovery and development of orphan drugs in the United States (US), the European Union (EU), and some parts of Asia. However, there are still many gaps in knowledge with regard to therapeutic tools and strategies. Intractable and rare diseases cause patients substantial physical suffering, psychological despair, and economic hardships due to bleak therapeutic outcomes and the lack of practical support in everyday life. The features of intractable and rare diseases and the increasing number of types of identified diseases make these diseases an important public health issue and a challenge to medical care worldwide. The following are specific aspects of research on intractable and rare diseases that need to be promptly promoted. An International Classification of Diseases (ICD) code to promote the definition and classification of intractable and rare diseases Intractable diseases, or “nanbyo” (literally “hard-to-treat diseases” in Japanese), mainly refer to rare diseases that have resulted mostly from unidentifiable causes and/or a lack of clearly established or curative treatments. According to the World Health Organization (WHO), rare diseases are rare and often debilitating or even life-threatening diseases or conditions with a prevalence of 0.65–1‰. The conventional view is that rare diseases as a whole affect around 10% of individuals worldwide, but the definition and categorization of rare diseases differ slightly by region. In the US, rare diseases are defined as diseases that affect fewer than 200,000 Americans (prevalence of < 0.75‰), while stipulated prevalence rates in other regions are < 0.5‰ in the EU, fewer than 2,000 patients (prevalence of < 0.11‰) in Australia, fewer than 50,000 patients (prevalence of < 0.4‰) in Japan, fewer than 20,000 patients (prevalence of < 0.4‰) in South Korea, or a prevalence of < 0.1‰ in Taiwan. The current outlook for identification of a specific rare disease and estimation of the true burden of rare diseases is bleak given the lack of proper classification and coding of rare diseases. Currently, there is no special coding system for rare diseases. The current ICD code that is used in most countries is not suitable for rare diseases. The absence of a universally recognized coding system is an obstacle for reliable registration of patients in national or international databases, preventing assessment of the economic and social effects of rare diseases. Fortunately, the good news is that the European Rare Disease Task Force of the Health and Consumers Protection Directorate General of the European Commission has set up a working group to collaborate with the WHO on the ICD-10, and the group is considering all other existing classifications to provide the rare disease community with a uniform system. A revised ICD code is urgently needed to both promote the definition and classification of intractable and rare diseases and to obtain accurate epidemiological data on these diseases at the national and international levels. Specific legislation to encourage discovery and development of orphan drugs Currently, orphan drugs — the medicinal products intended for the diagnosis, prevention, or treatment of rare diseases — are a major facet of how rare diseases are dealt with. In the past few decades, many countries have realized that orphan drugs will not lead to substantial sales under normal market conditions because of the high costs and risks of drug development, insufficient knowledge of the pathophysiological mechanisms of rare diseases that the drugs diagnose or treat, and difficulties in conducting clinical trials with small patient populations and a small potential market. Therefore, specific legislation to encourage the discovery and development of orphan drugs was enacted in many countries and regions, including the US in 1983, Japan in 1993, Australia in 1997, the EU in 1999, Taiwan in 2000, and South Korea in 2003. Incentives include financial subsidies, market exclusivity, tax credits, fee waivers, fast track approval, and protocol assistance, resulting in substantial improvements in the treatment of patients with a range of rare diseases. While China is actively preparing to regulate and encourage the development of orphan drugs, it still lags far behind the US, the EU, Japan, and other countries and regions with orphan drug legislation. Evidence has shown that all of the incentives have successfully encouraged the development of new pharmaceutical products to treat rare diseases. Prior to 2010, 352 orphan drugs were approved in the US, helping an estimated 12 million Americans, compared to only 10 such drugs in the decade preceding the Orphan Drug Act (1983). Similarly, 720 drugs had received orphan drug designation from the European Medicines Agency (EMA) and 63 designated orphan medicinal products have been authorized for marketing in the EU. Furthermore, data have shown that an average of 15 new orphan drugs are approved annually in the US and 10-12 new orphan drugs are approved annually in the EU. Thus, China and other countries without orphan drug legislation need to promptly establish domestic legislative regulations and incentives to encourage discovery and development of orphan drugs. Government-funded special biomedical research programs to enhance basic and applied research on intractable and rare diseases Biomedical research on intractable and rare diseases has provided insights into the pathologies of these diseases and revealed their underlying mechanisms. Such work may ultimately reveal possible avenues to therapeutics. Moreover, once biomedical research identifies suitable drug candidates and becomes more translational, it will garner industry attention, potentially leading to safe and effective orphan drugs. In Western countries, many research centers or projects have been established to support special biomedical research programs on rare diseases and development of orphan drugs, such as the Office of Rare Diseases Research (ORDR) established in the US in 1993 within the National Institutes of Health (NIH) and the Rare Disease Task Force (RDTF) established in EU in 2004 within the European Commission Public Health Directorate. In Asian countries, biomedical research on intractable and rare diseases has made great advances in Japan due to the systematic Specified Disease Treatment Research Program established in 1972 with the support of the Ministry of Health, Labor, and Welfare. As a result, special research programs and research grants from government sources to study 130 diseases increased to 10 billion Japanese yen in 2010. Recently, 214 diseases were designated for a second round of special research programs. In China, support for special biomedical programs on intractable and rare disease research comes mainly from the National Natural Science Foundation of China (NSFC). Data showed that 366 projects (involving 32 rare diseases) were funded by the NSFC from 1999 to 2007 with total funding of 89.358 million RMB and annual funding of about 10 million RMB, accounting for just 1/10th of similar funding in the US. Special biomedical research programs that enhance basic and applied research on intractable and rare diseases would benefit patients through better diagnosis and more treatment choices. Government-funded special biomedical research programs need to be promptly implemented in China and other countries to promote research on intractable and rare diseases. Patients' advocacy organizations and disease registry networks to provide vast information on intractable and rare diseases In recent years, progress has been made in the dissemination of knowledge and information by established patients' advocacy organizations, such as the National Organization for Rare Disorders (NORD) in the US and the European Organization for Rare Diseases (EURORDIS) in Europe, but the delay in diagnosis and treatment is still a huge challenge to cope with. A survey of 18,000 individuals found that 25% of patients waited for 5-30 years before being correctly diagnosed and 40% of patients were diagnosed incorrectly before they were correctly diagnosed. Furthermore, clinical studies on orphan drugs also face challenges due to the small size of the trial population and the fact that patients are often geographically dispersed. Disease registry networks need to be established to promote epidemiological and basic research and improve the clinical outcome for patients with intractable and rare diseases. In Western countries, some web-based resources, such as the Rare Diseases Clinical Research Network (RDCRN) in the US and the Orphanet in Europe, have been established in order to facilitate collaboration on clinical outcomes and to share accumulated experience so that patients with intractable and rare diseases are not delayed access to orphan drugs. More patients' advocacy organizations and disease registry networks need to be promptly established to facilitate interaction among patients, clinicians, researchers, the pharmaceutical industry, and governmental bodies with the ultimate goal of promoting intractable and rare disease research worldwide. (February 28, 2013)

A comparative study of European rare disease and orphan drug markets

BackgroundHealth Canada has defined rare diseases as life-threatening, seriously debilitating, or serious chronic conditions affecting a very small number of patients (~1 in 2,000 persons). An estimated 9 % of Canadians suffer from a rare disease. Drugs treating rare diseases (DRDs) are also known as orphan drugs. While Canada is currently developing an orphan drug framework, in the United States (US), the Orphan Drug Act (ODA) of 1983 established incentives for the development of orphan drugs.This study measured total annual expenditure of orphan drugs in Canada (2007–13) and estimated future (2014–18) orphan drug expenditure.MethodsOrphan drugs approved by the US Food and Drug Administration (FDA) in the US were used as a proxy for the orphan drug landscape in Canada. Branded, orphan drugs approved by the FDA between 1983 through 2013 were identified (N = 356 unique products). Only US orphan drugs with the same orphan indication(s) approved in Canada were included in the analysis. Adjustment via an indication factoring was applied to products with both orphan and non-orphan indications using available data sources to isolate orphan-indication sales. The IMS Health MIDAS database of audited biopharmaceutical sales was utilized to measure total orphan drug expenditure, calculated annually from 2007–2013 and evaluated as a proportion of total annual pharmaceutical drug expenditure (adjusted to 2014 CAD).ResultsBetween 2007 and 2013, expenditure was measured for a final N = 147 orphan drugs. Orphan drug expenditure totaled $610.2 million (M) in 2007 and $1,100.0 M in 2013, representing 3.3– 5.6 % of total Canadian pharmaceutical drug expenditure in 2007–2013, respectively. Future trend analysis suggests orphan drug expenditure will remain under 6 % of total expenditure in 2014–18.ConclusionsWhile the number of available orphan drugs and associated expenditure increased over time, access remains an issue, and from the perspectives of society and equity, overall spending on orphan drugs is lower relative to the number of patients affected with an orphan disease in Canada. The overall budget impact of orphan drugs is small and fairly stable relative to total pharmaceutical expenditure. Concerns that growth in orphan drug expenditure may lead to unsustainable drug expenditure do not appear to be justified.

The off-label use of drugs in oncology: a position paper by the European Society for Medical Oncology (ESMO)

Economic Evaluations of Orphan Drugs for Rare Kidney Diseases in Low- and Middle-Income Countries: A Bibliometric Systematic Review With Policy and Evidence Gaps Analysis.

Background and ObjectivesThere are significant challenges when obtaining clinical and economic evidence for health technology assessments of rare diseases. Many of them have been highlighted in previous systematic reviews but they have not been summarised in a comprehensive manner. For all stakeholders working with rare diseases, it is important to be aware and understand these issues. The objective of this review is to identify the main challenges for the economic evaluation of orphan drugs in rare diseases.MethodsAn umbrella review of systematic reviews of economic studies concerned with orphan and ultra-orphan drugs was conducted. Studies that were not systematic reviews, or on advanced therapeutic medicinal products, personalised medicines or other interventions that were not considered orphan drugs were excluded. The database searches included publications from 2010 to 2023, and were conducted in MEDLINE, EMBASE and the Cochrane library using filters for systematic reviews, and economic evaluations and models. These filters were combined with search terms for rare diseases and orphan drugs. A hand search supplemented the literature searches. The findings were reported by a compliant Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.ResultsTwo hundred and eighty-two records were identified from the literature searches, of which 64 were duplicates, whereas five reviews were identified from the hand search. A total of 36 reviews were included after screening against inclusion/exclusion criteria, 35 from literature searches and one from hand searching. Of those studies 1, 27 and 8 were low, moderate and high quality, respectively. The reviews highlight the scarcity of evidence for health economic parameters, for example, clinical effectiveness, costs, quality of life and the natural history of disease. Health economic evaluations such as cost-effectiveness and budget-impact analyses were scarce, and generally low-to-moderate quality. The causes were limited health economic parameters, together with publications bias, especially for cost-effectiveness analyses.ConclusionsThe results highlighted issues around a considerable paucity of evidence for economic evaluations and few cost-effectiveness analyses, supporting the notion that a paucity of evidence makes economic evaluations of rare diseases more challenging compared with more prevalent diseases. Furthermore, we provide recommendations for more sustainable approaches in economic evaluations of rare diseases.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-024-01370-2.

Rare diseases (RDs) present significant challenges worldwide, including Saudi Arabia (SA), where access to orphan drugs (ODs) is suboptimal. This study summarizes key insights from a multi-stakeholder workshop conducted in SA to explore and address challenges related to RD and OD accessibility. Strategies to improve the healthcare landscape for RDs in SA have also been recommended. A 1-day workshop, conducted at the Saudi Health Council in Riyadh, SA on 5 June 2023, gathered stakeholders from the government, private sector, pharmaceutical industry, legislators, regulators, providers, payers, academia, and insurance companies. Through a series of presentations, educational sessions, and plenary discussions, participants examined the current landscape of RDs in SA, identified barriers to accessing ODs, and recommended strategies and initiatives to improve the accessibility, innovation, and sustainability of ODs. The workshop highlighted key challenges recognized by a diverse group of 59 participants, including the absence of a national strategy, absent of local RDs and ODs definitions in the Saudi context, limited awareness and understanding of RDs among healthcare professionals, delayed diagnoses, scarcity of treatment and diagnosis centers for RDs, insufficient screening and prevention programs, regulatory hurdles in approving and importing ODs, and financial constraints. These challenges significantly impact patient access to ODs, imposing additional burdens on patients, families, healthcare systems, and society. The recommended strategies to enhance RD and OD accessibility include multifaceted approaches, such as increasing medical education and awareness, accrediting and investing in expanding the number of centers of excellence for RD diagnosis and management, streamlining regulatory processes for OD approval and importation, fostering international collaborations for knowledge exchange and capacity building, and implementing national policies to improve the affordability and reimbursement of ODs. Stakeholder collaboration is crucial to overcome the accessibility challenges of RDs and ODs. The development of comprehensive national RD strategies ensures equitable resource allocation, a national RD registry, and infrastructure improvements. These measures are vital for ensuring equitable access to ODs and the efficient provision of healthcare services in SA.

We are pleased to announce a new addition to SciencePower Publishing House, LLC journal collection: Journal of Rare Diseases and Orphan Drugs (JRDOD), a peer-reviewed open-access medical journal that publishes original research, reviews, case reports, and letters covering a broad field of its specialty.&#x0D; Why do we need a new journal? Because the science moves fast all around the Planet and new technology opened new horizons for the prevention and treatment of rare and genetically based disorders.&#x0D; Rare disease and disorders often need a multidisciplinary care team, deep knowledge of healthcare providers, and extensive patients’ and patient families’ support. It may take years until a disease is recognized and/or diagnosed. Spreading knowledge about rare disease conditions among biomedical scientists and physicians from the different subspecialty fields including genetics, pediatrics, cardiology, pulmonary, gastroenterology, rheumatology, neurology, dietary science, and other related disciplines is one of the goals of this journal, which we will be widely advertised within the medical community.&#x0D; Patients with special conditions could be “Rare, but Not Alone” and we want to add our voice to those patient advocacies.&#x0D; We also want to spread knowledge about orphan drugs. Well known fact that an orphan drug is a medication (pharmaceutical) that remains underdeveloped due to the lack of a company to find the drug profitable because the numbers of patients, who will benefit from the treatment, are small and so the potential market for new drugs to treat these rare diseases is also small. This situation fortunately somewhat changed in 1983, when the U.S. Congress passed the Orphan Drug Act. It facilitated and charged the orphan drugs' developmental landscape. Nowadays the FDA established the Office of Orphan Product Development (OOPD) to help with the development of orphan drugs (and other medical products for rare disorders), including FDA support for research grants.&#x0D; The international medical community has recognized the need to increase research and development of orphan drugs. We hope that our journal will be a small contribution to the promotion of wellbeing of people with rare disease conditions.&#x0D; Our publisher motto is "Superbi progressu aspiramus ad maximum" (the proud aspire to great promise).&#x0D; Please, consider submitting your next manuscript to the Journal of Rare Diseases and Orphan Drugs.

I read with great interest the AJHP news article about rare disease drugs.[1][1] I applaud the Journal for its efforts in increasing awareness of rare (orphan) diseases and spotlighting the development and procurement challenges associated with rare disease (orphan) drugs.[1][1]–[3][2] In the