What Drives ASMR of Orphan Drugs?

VA L U E I N H E A LT H 1 9 ( 2 0 1 6 ) A 3 4 7 – A 7 6 6

recommendation and reimbursement status varied from 0.1036 for AWMSG to 1 for TLV in case of orphans (without ultra-orphans) and from -0.2857 for SMC to 0.5 for AOTMiT. Among all agencies, only for AOTMiT and TLV in subsample of orphans the agreement between recommendation and reimbursement status was significantly higher than 0. No significant difference in agreement between subsample of orphan drugs (without ultra-orphans) and of ultra-orphans only was observed for any of agencies.  Conclusions: The distribution of recommendation types and reimbursement decisions was not associated with the orphan or ultra orphan status of considered drugs. PSY134 A Systematic Literature Review of Cysteamine Bitartrate Preparations in Patients with Cystinosis Van Der Weijden M, Peters M, Karabis A Mapi Group, Houten, The Netherlands

Objectives: To summarize all available clinical evidence for the different cysteamine bitartrate preparations in patients with cystinosis as identified through a systematic literature review (SLR).  Methods: We included studies reporting on the use of PROCYSBI® (cysteamine bitartrate) or Cystagon® (cysteamine bitartrate) in patients with cystinosis. All study designs and outcomes were included with no language restrictions. We searched MEDLINE, MEDLINE In-Process and EMBASE using Ovid® with a predefined search strategy through 19th January 2016.  Results: We included a total of 107 publications and 10 trial records, describing 107 studies, for data extraction. Of these, 13 studies describe PROCYSBI (n= 286 patients), 49 describe Cystagon (n= 1,587 patients) and in 53 studies the exact preparation was unclear (n= 1,020 patients). The vast majority of the studies used a non-randomized study design, with RCTs being scarce (1 study comparing PROCYSBI with Cystagon) and case reports being the most common study design (50 studies). Whilst there were more studies for Cystagon than PROCYSBI, a large proportion of the Cystagon studies consisted of case reports (41%).  Conclusions: A substantial evidence base for cysteamine bitartrate in nephropathic cystinosis was identified. However, the majority of the evidence was of relatively low quality. PSY136 Too Old for Treatment: Ageism in Chronic Lymphocytic Leukemia (CLL). A Narrative review of the Literature Lizán L1, Gabás C1, Castro-Gomez A2, Granados E2 1Outcomes’10, Castellon, Spain, 2Gilead Sciences, MADRID, Spain

Objectives: To appraise the literature relating age as a determinant of therapeutic decisions in CLL and search for evidence of ageism in the access to treatment of elderly patients.  Methods: Electronic databases [MedLine/PubMed] and grey literature [Google Scholar, congress proceedings, technical reports] were searched to identify publications investigating ageism in oncology, with a particular focus on 1) CLL treatment, 2) economic and social costs and 3) social value of the elderly; in order to comprehensively address the complex problematic of age discrimination. Studies in English or Spanish published until December 2015 were considered.  Results: A total of 31 publications were considered relevant to review: 8 articles related to the influence of age in decision making regarding CLL treatment, 13 studies about the cost-of-illness on elderly, and 10 publications underlining the value of the contribution of older persons to society. The results highlight that elderly CLL patients (> 70 years) are treated less effectively and frequently (p< 0.001), and therefore have lower response rates (p< 0.001), than younger ones. Clinical trials generally include patients who are 10 to 15 years younger than the median age at CLL diagnosis, therefore there is less consensus on how to manage aged patients. According to this, health status should be assessed by patients’ fitness rather than by their chronologic age. The social contribution of older people mainly occurs in terms of unpaid support (informal work, volunteering or within the family), representing 8.5% of the GDP in Spain. This contribution can be fostered by helping them to maintain good health. To accomplish this goal, new targeted therapies, which represent a profound advance in CLL treatment, can be especially useful due to their high efficacy and favorable benefit/risk ratio.  Conclusions: Discrimination by the age of CLL patients can be an important limiting factor to access to new treatment alternatives.

PSY137 Is the Orphanage Filling Up? Projecting the Growth and Budget Impact of Orphan Drugs in Europe Flostrand S1, Rodriguez I2, Maddox B3, Finch L3, Belulaj S3, Gould A4 Consulting Group, Paris, France, 2IMS Consulting Group, Madrid, Spain, 3IMS Consulting Group, Cambridge, UK, 4University of Cambridge, Cambridge, UK

1IMS

Objectives: Incentives to develop treatments for rare diseases have led to increasing numbers of orphan drugs (ODs) entering the European market. As budgets increase, there are questions regarding the sustainability of this growth. Previous projections have suggested this growth may plateau or slow; however, these studies have limitations. This study aimed to update and improve upon previous projections of orphan drug launches and assess the potential budget impact for major European markets.  Methods: We used EMA databases to identify approved and designated ODs. A total of 99 ODs with current sales were selected for analysis and a predicted conversion rate was developed to anticipate future launches. Historic IMS MIDAS sales data was combined with a forecast of these new OD launches to estimate the total annual sales of ODs from 2016-2025 in EU-5 markets. To add validity and estimate budget impact, IMS MIDAS data was used to forecast budget impact of ODs relative to the total pharmaceutical market.  Results: Over the past 5 years, the number of ODs obtaining market authorisation increased at 18% CAGR across EU-5, for a total budget impact over € 5.1Bn in 2015. Our model predicts that this growth will continue without plateau at a similar rate, reaching almost € 22Bn in 2025, equivalent to 14% of total drug spend. Analysing growth drivers, we find

A599

that rising prices is not a major factor, as it is outweighed by continued sales growth of established ODs and by the launch of new ODs.  Conclusions: Our forecast indicates that OD expenditure as a percent of total spend will increase significantly, putting pressure on healthcare budgets and raising the question of sustainability for OD spend. Healthcare policy makers will need to carefully consider OD funding and management, to ensure access can be maintained for the growing portfolio of these unique products. PSY138 What Drives ASMR of Orphan Drugs? Korchagina D1, Millier A2, Toumi M3, Aballea S2, Falissard B4 of Paris-Sud, Paris, France, 2Creativ-Ceutical, Paris, France, 3Aix-Marseille University, Marseille, France, 4Maison de Solenn, Paris, France

1University

Objectives: When undergoing a health technology assessment (HTA) in France, drugs are assigned ASMR score which represents the improvement in medical benefit bringing by the new therapy. Orphan drugs (ODs) are frequently granted higher ASMR compared to medicines for common diseases. The study aimed at identifying drivers of ASMR of ODs.  Methods: All ODs approved between 2000 and May 2015 by the European Medicines Agency (EMA) were identified. ASMR and other HTA details were available from HTA reports. The following parameters were studies: prevalence, severity, age of target population, availability of alternative treatment, ATC class, treatment line, type of clinical trial, comparator and primary endpoint, approval date, and HTA date. Association between ASMR and the parameters was studied in the bivariate analysis. A multinomial regression model was also developed. Only first approved indications were considered.  Results: From 102 OD approved by the EMA, 91 has undergone HTA in France and 88 were included in the analysis (one molecule was rejected and for two others ASMR score was not assessed). In the bivariate analysis ASMR were significantly associated with ATC class and disease prevalence. After the adjustment for other covariates, significant association remained only for ATC class (p= 0.02). Other parameters having a statistically significant impact on ASMR in multivariate analysis were age of targeted population (p< 0.01), disease severity (p= 0.03), treatment line (p= 0.04), type of clinical trial (p= 0.03) and HTA date (p< 0.01).  Conclusions: ASMR is a complex concept which includes multiple aspects of drug value. Number of ODs remains limited which may have resulted in lack of power. Several covariates showing no statistical significance in the bivariate analysis had a significant impact on ASMR in the multivariate analysis. This may indicate the presence of unstudied interaction, unbalanced sample size or high intra group variation. PSY139 Assessing the Gap Between Prioritized Conditions and Covered Conditions in Current Legislation for Rare and Orphan Diseases in Peru Hernández-Vásquez A1, Azañedo D2, Díaz-Seijas D3, Pussetto M4 de Buenos Aires, Buenos Aires, Argentina, 2Universidad Católica los Ángeles de Chimbote, Chimbote, Argentina, 3Instituto Nacional Cardiovascular-INCOR- EsSalud, Lima, 4 Argentina, Hospital Alemán, Buenos Aires, Argentina

1Universidad

Objectives: In 2014 Peru introduced legislation to provide coverage for rare and orphan diseases in the three subsectors of the health system (public, social security and private). The aim of this study is to describe the real access of patients with rare and orphan disease to insurance coverage in the public subsector.  Methods: Data from the Seguro Integral de Salud (the only public insurance and most widespread in Peru) was used to establish health insurance coverage according to the legislation between 2014 and 2015. Legislation included a prioritized list of 399 rare and orphan diseases categorized in Group 1 of very high priority (n= 8), Group 2 of high priority (n= 62), Group 3 of low priority (n= 27), and Group 4 of very low priority (n= 302). Descriptive analysis was applied by Stata.  Results: According to the Seguro Integral de Salud, a total of 39,192 patients with rare and orphan diseases were covered during the period 2014-2015: 157 (0.40%) were in Group 1; 7,234 (18.46%) in Group 2; 2,624 (6.70%) in Group 3 and 29,177 (74.45%) in Group 4. The analysis showed that only one disease (primary adrenocortical insufficiency) was covered for Group 1, and neutropenia, hereditary retinal dystrophy, and generalized idiopathic epilepsy and epileptic syndromes were the top covered diseases in Group 2, Group 3 and Group 4, respectively. Additionally, the number of patients with coverage has increased from 15,493 in 2014 to 23,699 in 2015, and diseases of very low priority, those in Group IV, were the most covered in both years.  Conclusions: Our study suggests that since legislation for rare and orphan diseases was implemented, lack of prioritization is one of the characteristics of the public insurance coverage in Peru. New legislation or changes in existing legal framework may be needed to ensure proper coverage for patients with these diseases.

PSY140 Cost-Effectiveness of Prophylaxis Compared to On-Demand Treatment in Severe Haemophilia a. Systematic Review Odnoletkova I Plasma Protein Therapeutics Association, Brussels, Belgium

Objectives: Prophylactic treatment of severe Haemophilia A (HA) with clotting factor concentrates became standard of care in many countries, however its costeffectiveness (CE) is controversial. This research critically appraises current evidence on CE of prophylaxis compared to on-demand treatment in patients with severe HA.  Methods: CE studies were searched in MEDLINE and Centre for Research and Dissemination. Study quality was assessed with Consensus Health Economic Criteria List. Costs were indexed to Euros 2015. Incremental cost-effectiveness ratios (ICERs) were compared.  Results: Eight publications met the inclusion criteria. The studies dated from 1996 to 2013 and evaluated relevant ICERs in the U.S., U.K., Germany, Netherlands, Sweden, Italy and Canada. ICERs were expressed as costs