Orphan Drug Policies Research Articles

Cross-national comparative study of orphan drug policies in Saudi Arabia, the United States, and the European Union

BackgroundRare diseases are chronic, serious, and life-threatening conditions that have not received sufficient attention from drug developers due to their rarity. Policies have been implemented to encourage research and incentivize the development of orphan drugs. However, the implementation of these policies has been inconsistent worldwide. ObjectiveThe primary aim of this study was to compare orphan drug policies in the United States, Europe, and Saudi Arabia (SA) and assess their impact on the number of approved indications. MethodLists of all drugs granted orphan designations and authorized for marketing in the United States, European Union, and SA were extracted using orphan drug lists available in regulatory body databases. The availability of these drugs, regarding their approval for orphan indication and designation, was assessed and classified using Anatomical Therapeutic Chemical codes. ResultA total of 792 orphan drug designations with at least one authorized indication were identified in this study. Of these, 92% were designated by the Food and Drug Administration (FDA), and 27% were designated by the European Medicine Agency (EMA). The FDA, EMA, and Saudi Food and Drug Authority approved 753, 435, and 253 orphan drugs, respectively. ConclusionFewer orphan drug approvals were found in SA than in the United States and Europe. This highlights the need to focus on rare diseases and orphan drugs and for policies to be created in SA to attract pharmaceutical markets and fulfill unmet orphan drug approval needs.

Commercial health plans use of patient subgroup restrictions: An analysis of orphan and US Food and Drug Administration-expedited programs.

BACKGROUND: Health plans apply utilization management criteria to guide their enrollees' access to prescription drugs. Patient subgroup restrictions (ie, clinical prerequisites for drug coverage) are a form of utilization management that have not been thoroughly investigated. OBJECTIVE: To examine the frequency with which large US commercial health plans impose patient subgroup restrictions beyond the US Food and Drug Administration (FDA) label in their coverage policies for orphan drugs and for drugs included in 1 or more FDA-expedited programs. To determine how consistently these patient subgroup restrictions align with eligibility criteria specified in each drug's pivotal clinical trial(s). METHODS: The Tufts Medical Center Specialty Drug Evidence and Coverage (SPEC) database was used, which includes coverage policies issued by 17 large US commercial health plans. SPEC contained 3,786 orphan drug policies and 4,027 FDA-expedited drug policies (current as of December 2020). SPEC data on plans' patient subgroup restrictions were assessed for the first objective. Each patient subgroup restriction was benchmarked against the corresponding eligibility criteria for a drug's pivotal clinical trial(s) for the second objective. To do so, the "Clinical Studies" section of the drug's FDA label was reviewed or, if necessary, the published manuscript describing the drug's pivotal trial(s). Patient subgroup restrictions were categorized as follows: (1) "consistent," the restriction and trial eligibility criterion are equivalent; (2) "same measure, more stringent," the restriction and trial eligibility criteria depend on the same measure, but the plan coverage is more restrictive; (3) "same measure, less stringent," the restriction and trial eligibility criteria depend on the same measure, but the plan coverage is less restrictive; and (4) "not consistent," the restriction and trial eligibility criteria depend on different measures. RESULTS: Health plans imposed patient subgroup restrictions in 20.2% of orphan drug policies (frequency varied by health plan, 11.7%-36.6%), and in 21.8% of FDA-expedited drug policies (frequency varied by health plan, 11.1%-47.9%). Of the 936 patient subgroup restrictions in orphan drug policies, 60.3% were categorized as consistent; 7.3% as same measure, more stringent; 12.0% as same measure, less stringent; and 20.5% as not consistent. Of the 1,070 patient subgroup restrictions in FDA-expedited drug policies, 57.5% were categorized as consistent; 6.7% as same measure, more stringent; 16.0% as same measure, less stringent; and 19.8% as not consistent. CONCLUSIONS: Patient subgroup restrictions for orphan drugs and FDA-expedited programs varied substantially across health plans, potentially resulting in inconsistent access to a given therapy across the approved patient population. Patient subgroup restrictions tend to be consistent with eligibility criteria specified in pivotal clinical trials. DISCLOSURES: This study was funded by Sarepta Therapeutics, Inc. Alexa C Klimchak and Lauren E Sedita are employees of Sarepta Therapeutics, Inc., and may own stock/options in the company.

Should rare diseases get special treatment?

Orphan drug policy often gives ‘special treatment’ to rare diseases, by giving additional priority or making exceptions to specific drugs, based on the rarity of the conditions they aim to...

Clinical trials for genetic diseases in Latin America.

Latin American geneticists have been contributing to the scientific development of Human and Medical Genetics fields since the early 1950s. In the last decades, as Medical Genetics is moving toward a new era of innovative therapies for previously untreatable conditions, the participation of Latin America in clinical trials is also increasing. This review discusses the particularities regarding funding, regulatory, and ethical aspects of conducting clinical trials for genetic diseases in Latin America, with an especial focus on Brazil, the largest country with the highest number of studies. Although there are still several barriers to overcome, the recent development of orphan drug legislation and policies for rare diseases in many Latin American countries indicates a growing opportunity for the participation of the region in international efforts for the development of new therapies for genetic diseases.

ORPHAN DRUG POLICY

Pharmaceutical industry is crucial for mankind and contributes in some way in socio economic development of the society through jobs, community welfare, and supply chains. Indian pharmaceutical companies are one of the largest markets in the world, estimated 10% of global production and 2% of world market. The industry is has shown significant growth in infrastructure development, producing wide range of pharmaceutical products with new technical advancements. The country is famous for producing and providing pharmaceutical products at much cheaper prices than the US and EU. However, the country lacks in investment in research on rare disease or orphan drugs. This paper tries to highlight the ways in which the market in orphan drugs can grow in India with the help of international partners.
 Objective: The objective of the study was to look at existing orphan drug policies and how we can aim at making it more equitable in India.
 Methods: Research is completely based on secondary data from online journals and government data. The study is analytical in its approach and is descriptive in nature.
 Results: Pharmaceutical companies invest less in Orphan drugs as they do not mark an assured profit with present investment.
 Conclusions: To maintain the interest of Indian pharmaceutical companies it is suggested that, Indian companies should work in collaboration with countries which lead in orphan drug markets.

Access and Unmet Needs of Orphan Drugs in 194 Countries and 6 Areas: A Global Policy Review With Content Analysis.

Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs. Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis. One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita= $10 875 vs $3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient= 0.57, P < .001). Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs.

ND1 ACCESS AND UNMET NEEDS OF ORPHAN DRUGS IN 194 COUNTRIES AND SIX AREAS: A GLOBAL POLICY REVIEW WITH CONTENT ANALYSIS

300 million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment when compared to other patients. Policies that optimise development, licensing, pricing, and reimbursement of orphan drugs are instrumental in addressing this neglected but significant burden. An overview of global orphan drug policies is proposed to inform policy development.

The work, goals, challenges, achievements, and recommendations of orphan medicinal product organizations in India: an interview-based study

BackgroundOrphan medicinal products (OMPs) are intended for the diagnosis, prevention, management or treatment of rare diseases (RDs). Each RD affects only a small fraction of the population, and therefore, historically, industry hesitated to undertake relevant research and development (R&D). In response, the governments of many countries came up with orphan drug policies and RD policies which were hugely successful in incentivizing companies to do so. In India, in the absence of any such policy until recently, there are very few organizations involved in RD R&D.ObjectivesWe wished to understand (i) the OMP Organizations’ (OMPOs’) areas of work and the nature of their work, (ii) their goals, (iii) the challenges they faced and how they were overcoming them, (iv) their achievements, and (v) their recommendations to the government to help their R&D, their success as commercial entities (where applicable), and patients’ access to their products or services.ResultsTen of the 14 OMPOs are companies, whereas four are not-for-profit organizations. Almost all of the OMPOs are heavily into R&D. Six have already made their products or services available to patients. Four plan to out-license their products after the pre-clinical phase or phase 1 trials, eight plan to cater to patients directly and two of the OMPOs have been established only recently and thus do not yet have any product or service to offer patients. Nine OMPOs import about 90% of the components in the production process, which comprises either capital or recurrent expenditure. For most, locally manufactured alternatives are not available or are of inadequate quality. Most of the OMPOs have had productive collaborations with local or foreign academics or hospitals for R&D, animal efficacy studies, clinical trials or providing services to patients. The main challenges for the OMPOs are the lack of adequate funding, supportive government policies, and a conducive ecosystem.ConclusionsThese OMPOs are pioneers in their respective fields in India, and despite the challenges, have achieved new levels of innovation. With suitable government policies, they could scale up and provide relevant products and services to the large number of RD patients in the country whose medical needs are largely unmet.

Orphan drug policies in different countries

Orphan drug policies in different countries

The impact of orphan drug policies in treating rare diseases.

This paper is based on Shalini Weerasooriya's Masters dissertation in Public Health at the University of Sheffield. A literature review was conducted to understand the role that orphan drug policies have played in the development of new treatments for rare diseases. The impacts of the policies were categorised as 'tangible' or 'intangible' and further synthesis identified 10 main themes such as incentives for investment, criteria for eligibility and assessment of drug applications and further guidance to industry during the drug development cycle. The review concludes that whilst policies have contributed positively towards improving the research and development of orphan drugs it has not exhausted its uses and must now shift its focus to facilitating greater accessibility and affordability of the treatments and that stakeholders are essential to the success of this process. Implications for practice are identified, for example the need to further update and refine the policy with changing demographics and advancing technologies and, in particular, greater collaboration and involvement through, for example, evidence based training programmes is recommended. It is concluded that focus must shift to address the gap between having available drugs and being able to access and afford them. F.J.

Real World Evidence (RWE) and Orphan drug policies in selected Central and Eastern European (CEE) Countries

The rationale for the initial project performed in the Central and Eastern European countries (CEE) was to assess and to share information from the region regarding drug policies. With this special cross countries comparison we aimed to analyze the significance of real world data (RWD) and real world evidence (RWE) for access to new therapies decisions and orphan drugs policies. We focused our comparison on the selected CEE countries (Poland, Estonia, Latvia, Croatia, Czech Republic and Hungary). It shows that although all of those countries are using HTA during reimbursement process, the approach towards RWD is different. In most of the cases RWD are not mandatory for reimbursement decisions, however in all the countries RWD can be submitted as supportive information for the decision making process.

PHP10 - Orphan Drug Policy and Access Dynamics in Japan

To understand the evolving patient access and coverage for orphan drugs in Japan. The study employed a pragmatic literature, industry, and policy review to determine the impact of national orphan drug policies such as priority review and accelerated approval of breakthrough treatments on Japanese reimbursement of orphan gene therapies, stem cell therapies, and PD-1/L1 inhibitors. Japan has facilitated orphan drugs’ market entry by prioritizing their market authorization process despite limited clinical data at launch. Orphan drugs may be approved in Japan with a published Phase II trial if the manufacturer agrees to conduct a future post-marketing authorization study; however, achieving regulatory approval may be challenging without inclusion of Japanese patients in clinical studies. Following global accelerated pathways to bring innovative products to patients more quickly, Japan has initiated its own system in 2015. Sakigake designation grants fast-tracked regulatory review and extension of the re-examination period; notably, orphan drugs already have extended 10-year pricing re-assessment timelines. Sakigake products need to meet criteria such as having a novel mechanism of action, addressing high unmet medical needs, or being commercialized in Japan before any other market. Six drugs have been designated so far - five by Japanese sponsors (including: DS-5141b – Duchenne; aducanumab – Biogen Japan; Nivolumab – Ono), and one by a multinational sponsor (Merck’s Keytruda); 3/6 target indications with notoriously high unmet need. Orphan drugs, including those under the Sakigake system, can benefit from the Chuikyo’s (pricing body) premium allowances for orphan and innovative products. Increasingly, orphan drugs are prioritized and given concessions during marketing authorization review, and they are eligible for pricing premiums due to their innovative mechanisms of action or their therapeutic area. If MHLW clinical trial criteria is met, the new Sakigake system looks to further facilitate and incentivize patient access of prospective orphan drugs.

Patient access to medicines in two countries with similar health systems and differing medicines policies: Implications from a comprehensive literature review.

Countries with similar health systems but different medicines policies might result in substantial medicines usage differences and resultant outcomes. The literature is sparse in this area. To review pharmaceutical policy research in New Zealand and Australia and discuss differences between the two countries and the impact these differences may have on subsequent medicine access. A review of the literature (2008-2016) was performed to identify relevant, peer-reviewed articles. Systematic searches were conducted across the six databases MEDLINE, PubMed, Science Direct, Springer Links, Scopus and Google Scholar. A further search of journals of high relevance was also conducted. Using content analysis, a narrative synthesis of pharmaceutical policy research influencing access to medicines in Australia and New Zealand was conducted. The results were critically assessed in the context of policy material available via grey literature from the respective countries. Key elements regarding pharmaceutical policy were identified from the 35 research papers identified for this review. Through a content analysis, three broad categories of pharmaceutical policy were found, which potentially could influence patient access to medicines in each country; the national health system, pricing and reimbursement. Within these three categories, 9 subcategories were identified: national health policy, pharmacy system, marketing authorization and regulation, prescription to non-prescription medicine switch, orphan drug policies, generic medicine substitution, national pharmaceutical schedule and health technology assessment, patient co-payment and managed entry agreements. This review systematically evaluated the current literature and identified key areas of difference in policy between Australia and NZ. Australia appears to cover and reimburse a greater number of medicines, while New Zealand achieves much lower prices for medicines than their Australian counterparts and has been more successful in controlling national pharmaceutical expenditure. Delays in patient access to new therapies in New Zealand have considerable implications for overall patient access to medicines; however, higher patient co-payments and relative pharmaceutical expenditure in Australia and its effect upon patient access to medicines must also be considered.

International differences in patient access to ultra-orphan drugs

ObjectivesReimbursement recommendations on (orphan) drugs are usually made at a national level and this can lead to variation in patient access to the same drug in different countries. We compared differences in patient access to ultra-orphan drugs between countries. Furthermore, we describe how reimbursed and non-reimbursed orphan drugs differ with respect to pharmacoeconomic properties. MethodsWe studied patient access to eight high-priced inpatient ultra-orphan drugs in nine countries. In addition, we determined whether differences with respect to cost per patient, budget impact and cost-effectiveness existed between orphan drugs with a positive and negative reimbursement status. ResultsReimbursement status was available for 78 orphan drugs, of which 56 (72%) were positive. Large differences were observed between countries; while two countries had a positive status for two out of nine ultra-orphan drugs, four countries had positive status for all drugs it assessed. A number of drugs were reimbursed only after price negotiations and/or through specific orphan drug policies. The average cost per patient, budget impact and incremental cost-effectiveness ratios were lower for ultra-orphan drugs with a positive reimbursement status than for those with a negative status, although only cost-effectiveness ratios were statistically significant. ConclusionsLarge differences in patient access to ultra-orphan drugs were observed between countries. Future research should examine if similar findings can be seen in other countries and with other orphan drugs, and it should also determine which other factors play a role in reimbursement status of orphan drugs.

Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries.

ObjectiveTo review existing regulations and policies utilised by countries to enable patient access to orphan drugs.MethodsA review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country.ResultsFifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country’s legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country’s pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access.ConclusionsOverall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases.

Orphan drug incentives in the pharmacogenomic context: policy responses in the US and Canada.

Advances in pharmacogenomic research and increasing industry interest in personalized medicine have important implications for the way that orphan drug policies are interpreted and applied. Concerns have been raised about the potential impact of pharmacogenomics and new genomic technologies on our understanding of how disease categories are delineated, and subsequently, how the concept of rare disease should be defined for the purposes of orphan drug policies. This article considers whether orphan drug legislation can be drafted in a way that will maximize benefits and minimize concerns relating to the impact of pharmacogenomics on orphan drug research and development. After reviewing the issues that may arise at the intersection of orphan drug policies and pharmacogenomics, this article will discuss the potential impact of pharmacogenomics at two critical points: orphan designation and approval of the drug product. At each of these points, the relevant aspects of current US orphan drug legislation are examined, focusing on the extent to which recent amendments may address concerns that have been raised previously. This analysis will then provide the foundation for a critical review and recommendations regarding the proposed new Canadian orphan drug framework.

A proposed definition of rare diseases for China: from the perspective of return on investment in new orphan drugs.

A prevalence threshold to define rare diseases is needed for orphan drug designation. Here, we propose a bottom-up approach to defining rare diseases for China, based on the minimum number of patients needed for the industry to make a reasonable profit on a new drug. To obtain this patient population size, we considered three factors: (1) the industry research and development cost per new drug; (2) the sales per new drug to recoup its research and development costs and generate profit; (3) the highest affordable cost for one patient’s treatment in a given healthcare system. Using this model, we estimate that, with the current level of innovation in the pharmaceutical industry in China, between 300,000 and 500,000 patients could be a reference threshold to define rare diseases. Compared with other proposals, this evidence-based definition is more useful for designing rare diseases and orphan drug policies for China.

Piedmont and Aosta Valley inter-regional network in the context of the Italian National Network for rare diseases.

In Europe rare diseases (RDs) are defined as “diseases with a prevalence in the European Union (EU) population of less than 5 per 10,000”. This definition includes a large group of more than 6,000 diseases, 90% of which are genetically determined and which potentially involve all organs1. RDs are therefore a very heterogeneous group as far as both clinical and epidemiological aspects are concerned. There are in fact RDs with less severe clinical manifestations and others with important ones which can compromise the quality of life and the life expectancy. Furthermore, some RDs have a prevalence approaching to the 5 per 10,000 limit and therefore affect a significant number of patients. Indeed, from the June 2005 to the December 2013 the Piedmont and Aosta Valley interregional register for RDs collected 21,062, with an estimated overall prevalence of RD of 45 patients on 10,000 inhabitants. Moreover half of the patients registered are affected by less than 20 diseases or groups of diseases (Table I) that represent the most important burden of care for the regional healthcare systems. On the other hand there are several with a much lower prevalence affecting a very small number of patients2. Table I Distribution of diseases covering 50% of reported diseases in the Piedmont and Aosta Valley Rare Diseases Registry. These latter often lack of timely and correct diagnosis and adequate treatment. Moreover, the world-wide orphan drug policies are associated with unacceptably high costs of newly developed drugs and inaccessibility of previously available drugs which become unavailable over time because of limited production by pharmaceutical industries3. Finally, despite the low prevalence of each disorder, the number of rare disease is fairly high. The European Commission reports that RDs affect a total of 6–8% of the population. Due to all these problems, and to the fact that RDs are often chronic and invalidating or cause early mortality, they represent a significant public health matter of concern in many countries.

Orphan drugs policies: a suitable case for treatment

Current orphan drug policies are unsatisfactory when viewed from almost all perspectives. Patients find that, although therapies are available for many rare conditions, access to care is sometimes restricted. Pharmaceutical manufacturers have responded to the incentives for research embodied in orphan drug legislation, only to find that funds are not made available to pay for therapies once developed. Those funding health care find that most orphan drugs do not justify funding based on standard value for money criteria, yet that they face political problems if they fail to provide funding for therapy. A literature review was conducted in order to determine the precise nature of the problems and to suggest potential solutions. Current orphan drug policies are not fit for the purpose and initiatives need to be taken in the areas of (1) clarifying society's views about the priority to be given to orphan drugs, (2) revising the arrangements for pricing and reimbursement of orphan drugs, (3) defining the priorities for research into rare diseases and (4) developing 'joined up' policies to deal with these issues. Without changes in the current policies, pharmaceutical companies will eventually cease responding to the incentives to develop orphan drugs, because they will increasingly be uncertain whether the drugs, if developed, will be reimbursed.

A Comparative Study on the Orphan Drug Policies

A Comparative Study on the Orphan Drug Policies