Availability Of Orphan Drugs Research Articles

Orphan drugs in Italy: availability and time-to-access at regional level

Introduction: There are an estimated 26 million rare disease patients in Europe, about 2 million in Italy. Access to orphan drugs has been evaluated nationally and internationally, and delays have been observed due to evaluation of price and therapeutic value. The objectives of this study are: to assess the availability of EMA-authorized orphan drugs at national and regional level; to study time trends and regional variability in consumption and spending, and to estimate the time to access in Italian regions. Methods: We evaluate the availability of EMA authorized orphan drugs in Italy. Based on data from the Traceability of medicines dataflow for period 2016-2021 we evaluate the expenditure, consumption and availability of orphan drugs in each region. To estimate the time to access we consider the days between the end of negotiation procedure and the first purchase by regions. Results: In 2021 in Italy are available 94% of EMA authorized orphan drugs. The expenditure and consumption have grown during the last decade. The availability is higher in bigger regions, that also take care of patients from smaller regions. The pro capite expenditure and consumption in DDD/1,000 ab die is similar in all the geographic area. Time to regional access is on average 123 days, that grows to 224 excluding the orphan drugs dispensed before the end of reimbursement procedure.

Long way to go: Progress of orphan drug accessibility in China from 2017 to 2022.

Introduction: Over 400 million patients worldwide suffer from rare diseases. Access to orphan drugs is, therefore, crucial for this population. China has been actively working on improving orphan drug accessibility in the past decades, especially since 2018 when the First National List of Rare Diseases was announced. This study aimed to evaluate the current status of orphan drug accessibility in China regarding availability, daily cost, and affordability. Methods: Market availability of orphan drugs in China was based on their approval status in China up to May 2022. Information on drug availability in hospitals and the cost of each drug from 2017 to 2021 was obtained from the database of the Science and Technology Development Center of the Chinese Pharmaceutical Association. Affordability was assessed by comparing the disposable daily income per capita to the cost of the defined daily dose of each drug. Results: Market availability rate was 44.3% by May 2022, and the average delay in drug approval in China compared to its orphan approval in the United States of America was 5.9 ± 6.07years. Drug availability in hospitals showed an upward trend, with availability in tertiary hospitals significantly higher than in secondary hospitals (~20%, p <0.0001). The eastern area was significantly higher in availability from 2019 onwards. Fifty-eight percent of the orphan drugs were still considered to have very low availability (<30%). The national median cost of the defined daily dose across all available orphan drugs had increased to 254.97 RMB in 2021. Only 34.98% of the orphan drugs were considered affordable when compared with the national average disposable daily income in 2021, and drug affordability decreased during the past 5years. Discussion: Changes in orphan drug regulations in China have enabled progress regarding the drugs' market availability, but the current status of drug availability at hospitals, drug cost, and affordability were not optimal. Legislation for encouraging domestic drug development and novel payment schemes for high-value drugs are essential to further improve the availability and cost burden of orphan drugs in China.

Exploring alternative financing models and early access schemes for orphan drugs: a Belgian case study.

Although some jurisdictions have implemented particular adjustments to accommodate often-expensive orphan drugs in their healthcare systems, availability of these drugs remains complex. This study investigates alternative financing models and early access schemes for orphan drugs in the context of the Belgian healthcare system. Three focus group discussions were held with a panel of eleven experts from the Belgian Drug Reimbursement Committee, the Colleges for Orphan Drugs, the pharmaceutical industry, physicians, ethicists and pharmacists. Retrieved data were pseudonymised, analysed and coded according to the Qualitative Analysis Guide of Leuven. Experts disfavoured the insulated fund as well as private insurance for financing orphan drugs, as, respectively, isolation of a separate budget and a mostly profit-driven mechanism would contradict the Belgian fundamental principle of solidarity. Moreover, an insulated fund could, albeit on a smaller scale, reproduce the same budgetary constraints as the general reimbursement system. As the Special Solidarity Fund is intended for urgent care and exclusively accommodates financial needs subject to eligibility criteria, its design would not allow general financing of orphan drugs. Overall, implementation of an alternative financing model was not endorsed, instead, improving the current reimbursement system was preferred. Suggestions mentioned were; increased collaboration and transparency, robust and quality real-world evidence but also digitalization of data. Alleviating administrative burden and simplifying the admission process of compassionate use program, medical need program and early treatment reimbursement should be prioritized to facilitate early access. Furthermore, a legal framework for off-label use could stimulate proper implementation. Efforts on collaboration of expertise centres and coordination of orphan drug databases across Europe could foster a robust data network to support orphan drug availability in individual countries. This research reveals that reassessing current financing models and early access schemes by eliminating inadequacies, may be more conducive than establishing alternative systems to increase availability of orphan drugs in Belgium. Other jurisdictions may rely on this information to review their own models of early access and financing to cultivate a more sustainable delivery of orphan drugs.

HPR30 Too Ultra-Rare for Care? Orphan Drug Availability for People Living With Ultra-Rare Respiratory Diseases in the Pre, Present and Post Pandemic Worlds

To compare the current and potential availability of treatments for seven index ultra-rare respiratory diseases before and after the peak of the COVID-19 pandemic. At the 2019 ISPOR EU Conference, a landscape review of available treatments for ultra-rare respiratory diseases was presented. Therefore, 3 years on, we sought to explore if treatment access has improved for ultra-rare respiratory diseases. A landscape review was undertaken to seek evidence of treatment developments for ataxia telangiectasia (AT), lymphangiomatosis (LYMF), pulmonary alveolar proteinosis (PAP), pleuroparenchymal fibroelastosis (PPFE), pulmonary alveolar microlithiasis (PAM), pulmonary dendriform ossification (PDO), and light chain deposition disorders (LCDD). Information from clinicaltrials.gov, orpha.net, the EMA and FDA archives and websites of five health technology assessment (HTA) bodies was narratively synthesised. The 2019 clinicaltrials.gov search identified 24 studies and the 2022 search 25 studies at various stages of the clinical trial process. They concerned PAP (2019/2022: 11/10), AT (6/10), LCDD (5/4), LYMF (1/0) and PPFE (1/1). No studies were identified for PAM or PDO. The 2019 review found treatments for AT and PAP were granted orphan status by the EMA and the FDA, and in 2021 the FDA granted orphan status to another AT treatment. Neither search found reimbursement submissions for any of the ultra-rare respiratory disease. There still remains an obvious lack of proven and available treatments for ultra-rare respiratory diseases. Over the past 3 years, only 1 new treatment has been granted regulatory approval and no treatments have yet to result in therapies that are licensed or approved by HTA bodies. It is our hope that as we enter the post-pandemic world, we as industry professionals and researchers start to adequately address the treatment needs of people living with these debilitating conditions.

Evaluating the national system for rare diseases in China from the point of drug access: progress and challenges

BackgroundThere are about 7000 rare diseases worldwide, of which only 5% of the diseases can be treated with medicines, showing that it’s important to improve patient access to orphan drugs. Recently, China has actively worked to set up a national system for rare diseases to improve the diagnosis and treatment capabilities and ensure the accessibility of drugs. However, the benefits of the system have yet not to be measured. This study aimed to provide an overview of orphan drug access based on the Compendium of China’s First List of Rare Diseases and National Network to Collaborate on Diagnosis and Treatment of Rare Diseases, expecting to map a blueprint for orphan drug access in China.MethodsFramework of China’s national system for rare diseases was summarized. We surveyed the availability and affordability of 79 approved orphan drugs based on the Compendium of China’s First List of Rare Diseases in 30 leading provincial institutions from 2017 to 2020. The availability was measured annually at 3 levels (market, hospital and drug), and affordability was reflected by comparing costs of daily defined dose with per capita income of urban and rural residents, with the National Basic Medical Insurance considered.ResultsThe market availability of orphan drugs in China showed an upward trend. As of 2020, the median hospital-level availability was 41.1% (increased by 1.5 times), highly available drugs increased by 16.5%. There were 64/74 orphan drugs that were affordable to rural/urban residents with the National Basic Medical Insurance considered (an increase of 14.1%), and the urban–rural gap of affordability ratio was narrowed (down by 6.0%). Comprehensive analysis showed the proportions of drugs with better availability and affordability in urban and rural areas by 2020 were 39.4% and 32.3%, respectively, which had increased but were still at a low level.ConclusionsChina’s national system for rare diseases has made great progress in orphan drug access, indicating that it’s been functioning under the joint reformation of medical treatment, medical insurance and medicines supply. The list of rare diseases will be updated and collaboration in networks will be enhanced to further improve the system.

The impact of the rare disease and Orphan Drug Act in Taiwan.

The Rare Disease and Orphan Drug Act (the Act) was enacted in 2000 in Taiwan for the facilitation of the research, development, and accessibility of orphan drugs and special nutritional foods; for the prevention and early diagnosis of rare diseases; and for providing intensive care for patients with rare diseases. The aim was to investigate the impact of the Act on the availability and use of orphan drugs in Taiwan in the hope of identifying the remaining challenges and possible solutions to assist future policy making, which may be applicable in other countries as well. The information and statistics for rare diseases and orphan drugs retrieved from the official annual reports and documents were analyzed. There were 225 diseases recognized as rare diseases, and one-third (75/225) of them were congenital metabolic disorders. Among the 110 designated orphan drugs that could apply for listing in the National Health Insurance (NHI) Pharmaceutical Benefits and Reimbursement Scheme, approximately half (62/110) of them were granted marketing authorization. While the NHI program compulsory for all citizens increased patient accessibility to orphan drugs, the rapidly increasing economic burden became an urgent issue for the government. Emerging gene therapies may be the solution to unmet medical needs and also a financial obstacle to tackle. The Act increased the availability of orphan drugs while the NHI system facilitated patient access, which benefited many patients with rare diseases in Taiwan. However, the soaring economic burden was noticed and was anticipated to aggravate. More communication and cooperation between stakeholders is critical in finding solutions for the long-term sustainability of the NHI system.

PRO71 The Orphan Drugs Access in Italy: The Role of the EARLY Access Tools in the Last FIVE YEARS

In Italy, several provisions govern the access of drugs approved by EMA before the NHS reimbursement. It is the so-called early access. This study aims to analyse the impact of early access tools (Law 648, Law 326 and compassionate use programmes (CUPs)) on access to orphan drugs (ODs). The drugs’ panel was built with all the ODs approved by EMA between 2015 and 2020. Info about Law 648, 326 and CUPs are available on AIFA’s website, OSMED Report and Italian OJ. Between 2015 and 2020 EMA’s CHMP recommended 64 ODs. 41/64 ODs(64%) are marketed. Of these, 22/41(54%) are classified in H class, 9/41(22%) in A, 7/41(17%) in C and 3/41(7%) in C(nn). 20/41(49%) ODs currently marketed had an early access: 10/41(24%) through CUPs, 6/41 (15%) through Law 326, 4/41(10%) through Law 648 and 3/41(7%) ODs launched in C(nn) class before their reimbursement. 13/41 ODs marketed (32%) with EA were also recognized as innovative by AIFA. Of the 23 ODs not marketed, 7(30%) are available through EAPs (4/23 (17%) CUP; 3/23(13%) 326). Of the 16 ODs not marketed nor available via EAP, 5 are under AIFA negotiation, 2 are in A class, 1 is in H class, 1 is in C class and 5 are in C(nn) class. The median negotiation time was 287 days for the ODs with early access vs 327 for ODs without . The access to the AIFA Fund 5% (Law 326) was requested for 20 patients (expenditure of about 7.4 MIO €) in 2016 and for 60 patients (expenditure of about 12.9 MIO €) in 2017. Our analysis highlighted a positive impact of various early access tools on the availability of ODs.

Measuring parent proxy-reported quality of life of 11 rare diseases in children in Zhejiang, China

BackgroundIt has become increasingly important to measure the health-related quality of life (HRQoL) of rare diseases in children and adolescents in recent decades. Much attention has been paid to investigate the HROoL of a specific rare disease by self-report in previous studies. This study aimed to evaluate and compare the HROoL of 11 rare diseases in Chinese children by parent proxy-report, to explore the factors associated with HROoL of patients, and to understand the problems of most concern.MethodsA total of 651 children aged from 2 to 18 were enrolled from the Children’s Hospital Affiliated Zhejiang University in 2018. Their parents completed the parent proxy-report version of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™ 4.0). Independent samples t-test, one-way ANOVA, or Kruskal–Wallis H test was used to compare HROoL scores between groups. Multilevel linear regression models with random intercept were applied to analyze the relationship between socioeconomic variables and both the total score and subdomain scores.ResultsThe total PedsQL scores of Patent ductus arteriosus (PDA), Infantile agranulocytosis, Autoimmune thrombocytopenia (ITP), Polysyndactyly, Hirschsprung disease, Cleft lip and palate, Tetralogy of fallot, Myasthenia gravis, Guillain–barre syndrome, Glycogen storage disease, and Langerhans cell histiocytosis children were 79.65 ± 5.46, 95.88 ± 3.48, 71.39 ± 3.27, 91.77 ± 6.35, 76.18 ± 6.92, 96.33 ± 4.22, 77.85 ± 8.90, 95.99 ± 3.31, 85.77 ± 4.56, 82.97 ± 4.13 and 77.6 ± 5.15, respectively. Age was significantly associated with physical functioning, school functioning, and psychosocial health scores. The household registration place was significantly related to the total score. The most urgent desire of patients was to reduce the overall medical costs.ConclusionsThis study showed that patients with PDA had the lowest physical functioning score, while patients with ITP scored the lowest in the emotional functioning, social functioning, school functioning, psychosocial health, and total scores. Incentive policies should be further adopted to improve orphan drug availability and reduce the economic burden of rare diseases.

PND134 HTA AND ACCESS FOR ORPHAN DRUGS: IDENTIFICATION OF 4 CRITICAL DIFFERENCES BETWEEN UK AND US PATHWAYS

Exponentially increasing orphan drug prices has negatively impacted reimbursement decisions, limiting patient access. Availability of orphan drugs varies jurisdictionally, as do the HTA and access processes. To compare the UK and US, four mutual themes will be identified to highlight the differences in orphan drug processes and the associated effects. A systematic literature review was conducted on publications, indexed in PubMed and EMBASE, to identify, via scoring and ranking, comparative and contrasting themes between the UK and US. Articles published after 10/06/2016 were selected using inclusion and exclusion criteria and were confirmed for validity using CASP checklists. Findings were tested and confirmed through interviews, following predefined discussion guides with experts in orphan drug HTAs and market access. Four themes emerged from the literature review, which were used to compare the UK and US: HTA pricing, reimbursement and funding, time-to-market, and patient access and prescribing. Free-pricing between US healthcare providers resulted in varying prices for the same drug, whereas the UK-based NICE HTA outcomes achieved fixed-pricing for all patients. Likewise, due to the US competitive pricing environment, orphan drugs were priced considerably higher than in the UK. Both countries offered public funding opportunities, aiding treatment financing and access. However, considerably more orphan drugs received reimbursement in the US than the UK. Both countries offered early access, or fast-track approval, in cases tackling significant unmet need. Analysis using the four criteria identified that orphan drug prices in the US were considerably higher than the UK. Both countries offered accelerated or early access schemes and public funding, yet patient access was challenged due to reimbursement and funding limitations. Although market access is higher in the US, varying healthcare plan portfolios, and price variability, limits patient access. The UK reimburses fewer orphan drugs, but all UK patients have access to reimbursed treatments.

PSY31 - Europe-China Comparison of Orphan Drugs Approvals

Rare diseases, today, constitute a public health issue. Specific legislations to incentivize the development of orphan drugs were adopted in Europe in 1999, whereas no specific legislation was established in China until now. Therefore, our study aimed to assess the availability of orphan drugs in China compared to Europe and to discuss potential challenges facing orphan drugs in China. The official websites of European Medicine Agency (EMA) and China Food and Drug administration (CFDA) were searched to identify approved orphan drugs up until 01/03/2018 in Europe and China, respectively. The delays in approval were calculated and delay rationales were discussed. A total of 102 orphan drugs were approved in Europe. Among these 102 orphan drugs, 15 (14.7%) were approved in China. Only the drug Dacogen® was approved earlier in China than in Europe, with a time interval of 3.98 years. The median delay was 3.29 years. The shortest and longest time lags were 55 days and 14 years, for the drugs Nexavar® and Zavesca®, respectively. Delays in approval may be due to several reasons: 1) the lack of a clear definition of rare disease in China, 2) the requirement of completing a phase 1 study outside China before implementing clinical trial in China, 3) manufacturers’ decision because of complex procedures, concerns regarding the profitability and uptake in the market 4) other reasons include staff shortage in drug evaluation center and inadequate intellectual-property protection in China. Special approval procedure for priority review of orphan drugs has been established as of 2017 in China. In addition, orphan drugs may also achieve faster reimbursement by national drug price negotiation. Improvement is expected for orphan drugs access. However, more efforts and a specific legislation for orphan drugs are still needed in China to ensure rapid patient access to orphan drugs.

Rare Diseases and Orphan Drugs Accessibility in Bosnia and Herzegovina.

Introduction:Rare diseases are becoming more and more important since awareness is increasing. There are a lot of initiatives to ensure access to orphan drugs intended to treat these diseases but due to high price patients have low access and policy makers and payers are struggling with costs and assuring patient access rights to the available medication.Aim:Objective of this study is to assess current situation regarding rare diseases in Bosnia and Herzegovina (BiH) and availability of orphan drugs. Four domains are examined: legislation and policy, diagnostics and research, patient organizations and reimbursement and availability of medicines for rare diseases.Results:There are official programs and legislation ground for rare diseases in both entities of BiH: Republic of Srpska (RS) and Federation of BiH (FBiH). Diagnostic and genetic counseling are available but only for few rare diseases. Patient organizations are formed and active but still without engagement in some of international organizations. There are no special reimbursement criteria for orphan medicines. Number of reimbursed medicines is significantly lower than those on ORPHANET list, 67 and 26 in RS and FBiH respectively. Huge difference in number of reimbursed medicines within the country entities may be consequence of counting method.Conclusion:Even thou rare diseases in BiH are recognized in countries official programs and documents, with patients having their organizations, much more have to be done in availability of medicines and diagnostics in the rare disease field. Insufficient funds are huge obstacle toward this goal. New methods of medicine evaluation are need and recommended in order of better availability.

The availability and affordability of orphan drugs for rare diseases in China.

BackgroundOrphan drugs are intended to treat, prevent or diagnose rare diseases. In recent years, China healthcare policy makers and patients have become increasingly concerned about orphan drug issues. However, very few studies have assessed the availability and affordability of orphan drugs for rare diseases in China. The aim of this study was to provide an overview of the availability and affordability of orphan drugs in China and to make suggestions to improve patient access to orphan drugs.MethodsTwo components of the availability of orphan drugs were examined. Market availability was assessed by the extent to which orphan drugs were marketed in China with a comparison to orphan drugs in international markets, such as the U.S., EU and Japan. We conducted surveys and collected data from 24 tertiary public hospitals in China to measure hospital-level availability of orphan drugs. The affordability of orphan drugs was calculated using hospital dispensary prices and was expressed as days of average daily income required for the cost of a course of treatment. Affordability was also analyzed under the Chinese basic medical insurance system.ResultsOrphan drugs approved in the U.S., EU and Japan had 37.8 %, 24.6 % and 52.4 % market availability in China, respectively. Median availability of 31 orphan drugs surveyed at the 24 tertiary public hospitals was 20.8 % (very low). Within a periodic treatment course, the average treatment cost of 23 orphan drugs is approximately 4, 843. 5 USD, which equates to 505.6 days of per capita net income for an urban resident with a middle income (187.4 days for a high-income urban resident) or 1,582.8 days’s income for a rural resident with a middle income (657.2 days for a high-income rural resident). Except for homoharringtonine, 22 orphan drugs for 14 rare diseases were unaffordable for the most of residents in China. With 5 % out-of-pocket expenses, only three generics could be afforded by middle-income residents, whereas seven drugs for high-income urban residents.ConclusionsThe Chinese government can take more responsibility for improving the availability and affordability of orphan drugs through setting up incentive policies and public platforms for sharing of orphan drug information. Control of the high price of orphan drugs, combined with a joint funding model from both government and private enterprise can efficiently reduce the economic burden of affected patients in China.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0392-4) contains supplementary material, which is available to authorized users.

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.

Tyrosinemia type I: clinical and biochemical analysis of patients in Mexico

Introduction. Hepatorenal tyrosinemia (HT1) is a treatable, inherited, metabolic disease characterized by progressive liver failure with pronounced coagulopathy. The aim of this study is to describe the clinical, biochemical, and histopathological findings in a group of Mexican HT1 patients and their outcome.Material and methods. Medical records of HT1 patients diagnosed between 1995 and 2011 were analyzed. The diagnosis of HT1 was confirmed by detection of succinylacetone in urine or blood.Results.Sixteen non-related HT1 cases were analyzed. Mean age at clinical onset was 9 months, and the mean age at diagnosis was 16.3 months. Main clinical findings were hepatomegaly, splenomegaly, cirrhosis, liver failure, tubulopathy, nephromegaly, Fanconi syndrome, seizures and failure to thrive. Histopathological findings were cirrhosis, fibrosis and steatosis. The HT1 group had a mortality rate of 78%. Patients who received supportive care or nutritional treatment had a 3-year survival rate of 10%. For those who underwent liver transplantation, the 6-year survival rate was 60%. In most cases pharmacological treatment with nitisinone and special dietary products were not available. The leading causes of death were fulminant liver failure, metastatic hepatocellular carcinoma, and porphyria-like neurologic crisis. Newborn screening programs in combination with the availability of orphan drugs, proper monitoring, genetic counseling, and clinical practice guidelines are needed to enable physicians to identify the disease, delay its progression, and improve patients’ quality of life.Conclusion. The devastating natural history of HT1 is still observed in Mexican patients because they are not diagnosed and treated during the early stages of the disease.

PCN134 Expenditures and Availability of Orphan Drugs in the Czech Republic: Seven Year Experience (2004 – 2010)

PCN134 Expenditures and Availability of Orphan Drugs in the Czech Republic: Seven Year Experience (2004 – 2010)

New opportunity for orphan drug development in Japan: Early exploratory clinical trial bases promote drug translation from basic studies to clinical application

In Japan, although orphan drug legislation has been established in 1993 to encourage drug research and development (R&D) for intractable and rare diseases, nearly half of the orphan drugs in the Japanese market originated from the European Union (EU) or the United States of America (USA). Availability of orphan drugs for intractable and rare diseases is compounded by the "drug lag" phenomenon, which is mainly caused by the imperfect clinical trial environment in Japan. In recent years, the Japanese government paid great attention to development of innovative drugs and medical devices which originated from Japan. With financial support and institutional guarantees from government, the project of "Early Exploratory Clinical Trial Bases for Specific Research Areas" was launched in 2011 and 5 institutions were selected as the national early exploratory clinical trial bases for specific research areas including cancer, cerebral and cardiovascular diseases, neuropsychiatric disorders, and immunological intractable diseases. The early exploratory clinical trial bases offer a new opportunity for drug development for immunological and neuropsychiatric intractable diseases, thereby promoting orphan drug translation from basic studies to clinical use.

Availability of and Access to Orphan Drugs

Market authorization does not guarantee patient access to any given drug. This is particularly true for costly orphan drugs because access depends primarily on co-payments, reimbursement policies and prices. The objective of this article is to identify differences in the availability of orphan drugs and in patient access to them in 11 pharmaceutical markets: Australia, Canada, England, France, Germany, Hungary, the Netherlands, Poland, Slovakia, Switzerland and the US. Four rare diseases were selected for analysis: pulmonary arterial hypertension (PAH), Fabry disease (FD), hereditary angioedema (HAE) and chronic myeloid leukaemia (CML). Indicators for availability were defined as (i) the indications for which orphan drugs had been authorized in the treatment of these diseases; (ii) the application date; and (iii) the date upon which these drugs received market authorization in each country. Indicators of patient access were defined as (i) the outcomes of technology appraisals; (ii) the extent of coverage provided by healthcare payers; and (iii) the price of the drugs in each country. For PAH we analysed bosentan, iloprost, sildenafil, treprostinil (intravenous and inhaled) as well as sitaxentan and ambrisentan; for FD we analysed agalsidase alfa and agalsidase beta; for HAE we analysed icatibant, ecallantide and two complement C1s inhibitors; for CML we analysed imatinib, dasatinib and nilotinib. Most drugs included in this study had received market authorization in all countries, but the range of indications for which they had been authorized differed by country. The broadest range of indications was found in Australia, and the largest variations in indications were found for PAH drugs. Authorization process speed (the time between application and market authorization) was fastest in the US, with an average of 362 days, followed by the EU (394 days). The highest prices for the included drugs were found in Germany and the US, and the lowest in Canada, Australia and England. Although the prices of all of the included drugs were high compared with those of most non-orphan drugs, most of the insurance plans in our country sample provided coverage for authorized drugs after a certain threshold. Availability of and access to orphan drugs play a key role in determining whether patients will receive adequate and efficient treatment. Although the present study showed some variations between countries in selected indicators of availability and access to orphan drugs, virtually all of the drugs in question were available and accessible in our sample. However, substantial co-payments in the US and Canada represent important barriers to patient access, especially in the case of expensive treatments such as those analysed in this study. Market exclusivity is a strong instrument for fostering orphan drug development and drug availability. However, despite the positive effect of this instrument, the conditions under which market exclusivity is granted should be reconsidered in cases where the costs of developing an orphan drug have already been amortized through the use of the drug's active ingredient for the treatment of a common indication.

Les médicaments orphelins commercialisés en France (2001-2005) : information officielle et spécificités

In year 2000, two european regulations have been adopted in order to increase the availability of orphan drugs in the European Union. To describe the current orphan drug market in France, a cross sectional analysis was conducted, five years later, taking account of publicly available informations, including designation, registration, reimbursement. These informations are mostly available on the Internet. Eighteen orphan drugs were marketed in France in November 2005, with restricted prescription and dispensing conditions. Four of them were available before registration for compassional use. Eight will be reassessed soon, with complementary data requested by health authorities. Informations about orphan drugs are scattered on different French or European websites, which complicate access for health professionals. The opinions of "Commission de Transparence", which assess utility of drugs, give some precisions for each orphan drug (prevalence of the disease, therapeutic alternative, etc.).