Determinants of Orphan Drug Prices in Italy and the UK

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OD have experienced shortages, of which 29 (44%) were resolved with an average shortage duration of 639 days. OD shortages were observed for 19 oncology products (10% of oncology OD) and 14 endocrinology products (22% of endocrinology OD).  Conclusions: Although OD fill a gap in care for the treatment of rare conditions, the iterative small volume manufacturing process leads to a large number of lapses in drug availability in the US. Despite FDA strategic plan for preventing and mitigating drug shortages (October 2013), remaining OD shortages still pose an enduring challenge to patient care and in many instances there are no alternative therapies, which results in many patients left untreated. New effective policies are warranted to address this public health issue. PSY123 War Rages Between Infliximab Biosimilars and Their Originator Loubiere A, Bocquet F, Paubel P General Agency of Equipment and Health Products (AGEPS), Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France

Objectives: This study aims to assess the level of competition between infliximab biosimilars (BIOSIM-INFLIX) and their originator (Remicade/infliximab, J&J/ Merck) (ORIGIN-INFLIX) by analyzing the key global infliximab markets and the drivers of the BIOSIM-INFLIX uptakes.  Methods: Data on medicine volumes, values and ex-manufacturing prices for BIOSIM-INFLIX and ORIGIN-INFLIX in the EU, in South Korea and in Japan were provided by IMS Health. Volumes were calculated in DDD (Defined Daily Doses) and Weighted Average Price (WAP) in euros/DDD.  Results: In 2015, the highest BIOSIM-INFLIX uptake was found in Norway (67.8%) and the lowest was reported in Japan (1.1%). In EU countries where BIOSIM-INFLIX were marketed in 2015, their uptakes are still low (e.g. France, the UK, Germany, Italy and Spain with respectively 4.1%, 9.0%, 9.2%, 10.7% and 12.8% uptakes). In countries where BIOSIM-INFLIX are marketed since 2013, their uptakes are higher (e.g. Portugal, Czech Republic and Finland with respectively 15.1%, 20.6% and 32.5% uptakes). All countries have dominant hospital distributions for infliximab except Germany, Japan and Czech Republic which have mixed retail/hospital distributions. Germany is the country where BIOSIM-INFLIX is the most expensive (WAP =  21.7€ /DDD) and Norway the country where it is the cheapest (WAP =  4.4€ /DDD with a discount of 68.8% versus ORIGIN-INFLIX). But the relative price of BIOSIM-INFLIX versus ORIGIN-INFLIX does not always seem correlated to BIOSIM-INFLIX uptakes (e.g. in South Korea, the biosimilar uptake is 26.0%, whereas the WAP difference between BIOSIM-INFLIX and ORIGIN-INFLIX is of -5.2%; in Japan (BIOSIM-INFLIX uptake of 1.1%) this difference amounts to -33.2%).  Conclusions: Infliximab markets have proven to be highly country-specific. Today, the competition between BIOSIM-INFLIX and ORIGIN-INFLIXseems not mainly based on prices, but on local decision-making and purchasing process. Due to the limited experience on the use of BIOSIMINFLIX our results have to be confirmed in the future. PSY124 Association Between Orphan Drug Prices and Therapeutic Area Korchagina D1, Toumi M2, Pliez A3, Millier A4 of Paris-Sud, Paris, France, 2Aix-Marseille University, Marseille, France, 3Hôpital de la Conception, Marseille, France, 4Creativ-Ceutical, Paris, France 1University

Objectives: Orphan drugs (OD) benefit from increasingly high prices leading to increased business interest from large pharmaceutical companies. The objective of this research is to compare ODs prices in France between different therapeutic classes.  Methods: All ODs approved between January 2000 and May 2015 were identified from the official website of the European Medicines Agency. When available, OD prices were collected from the official French database Ameli. Yearly price was computed for each product. Products were sorted by therapeutic class according to ICD 10. Only first approved indication and initial price at launch were considered.  Results: Price was available for 68 ODs from 98 approved by the EMA. Median price for all ODs was € 35,643 (minimum € 1,473; maximum€ 912,600). Price distribution was skewed justifying the use of median price. Number of products and median cost were: endocrine metabolic disorders [20_€ 194,804], immune disease [5_€ 43,680], circulatory [5_€ 32,850], oncology [n= 27; median= € 32,099], respiratory [4_€ 19,152], central nervous system [4_€ 6,944], others [3_€ 7,687]. Oncology product prices appear to be the fourth on the list while being the most frequent identified products (n= 27). Endocrine and metabolic disorders are by far the most expensive, followed by immune disorders, and circulatory.  Conclusions: The increase approval of oncology ODs does not seem to be primarily driven by the high price of products in this area, while this may well be the case for metabolic endocrine ODs with 20 products. Although median prices are in general high, there is a large variability within and between therapeutic areas that may not be justified by the added value or level of unmet need. PSY125 Determinants of Orphan Drug Prices in Italy and the UK Korchagina D1, Millier A2, Toumi M3, Vataire A2, Falissard B4 of Paris-Sud, Paris, France, 2Creativ-Ceutical, Paris, France, 3Aix-Marseille University, Marseille, France, 4Maison de Solenn, Paris, France

1University

Objectives: The study aimed at identifying the determinants of orphan drug (OD) prices in Italy and the UK.  Methods: All ODs approved between 2000 and May 2015 by the European Medicines Agency (EMA) were identified. The prices were extracted from the Compendio Farmaceutico Telematico database and the British National Formulary. Annual treatment costs were calculated based on OD prices and dosing regimen. The following parameters were used: prevalence, severity, age of target population, availability of alternative treatment, ATC class, treatment line, type of clinical trial, comparator and primary endpoint, approval date, commercialisation

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date (Italy only), delay between the approval and commercialisation (Italy only) , drug class (Italy only), recommendation of the NICE (UK only). Association between annual costs and the parameters was studied in the bivariate analysis. Moreover, a generalized regression model with negative binomial distribution was developed.  Results: The price was available for 78 ODs in Italy and 82 in the UK. The median (range) OD costs in Italy and the UK were € 40,255 (€ 758-€ 823,617) and € 34,043 (€ 1003-€ 753,166). Disease prevalence, alternative treatments, and ATC class were significantly associated with treatment cost for Italy and the UK. When adjusting for other covariates there were no significant association with prevalence and ATC. In the multivariate analysis for Italy, a significant association was observed for age of target population, alternative treatments, treatment line, type of study, commercialisation date and the delay between the approval and commercialisation. For the UK, only age of target population and approval date were significant, alternative treatments (p= 0.071), treatment line (p= 0.059), type of study (p= 0.093) and NICE recommendation (p= 0.051) were nearly significant.  Conclusions: Multiple parameters seem to impact OD prices. Number of drugs remains small that may have resulted in lack of power. Listed prices may differ from real prices if patient access schemes are applied. PSY126 Association Between Disease Prevalence, Drug Price and ASMR for Orphan Drugs in France Korchagina D1, Toumi M2, Pliez A3, Millier A4 of Paris-Sud, Paris, France, 2Aix-Marseille University, Marseille, France, 3Hôpital de la Conception, Marseille, France, 4Creativ-Ceutical, Paris, France 1University

Objectives: Rarity is often considered as the driver of high orphan drug (OD) prices. The objective of this research is to identify the relationship between OD annual treatment cost in France and the rarity, as well as OD cost and acknowledgement of additional benefit (ASMR), and, finally, between ASMR and cost. Methods: We identified all ODs approved by the European Medicine Agency (EMA) between January 2000 and May 2015. OD costs were calculated based on prices collected from the official French database Ameli and dosing regimen. Prevalence was available from the EMA website. We only considered first indications and initial prices. We looked at the correlation between each pair of the three variables and we identified the best fit equation type for cost/prevalence relation.  Results: Cost and prevalence were significantly correlated with R2 coefficient of 0.105 and Pearson correlation coefficient of -0.325 (p= 0.0069). The best function fit was logarithmic, based on the root mean square error criteria. Lower prevalence was associated with higher costs, although, there was significant variation between costs for a similar prevalence. For products granted ASMR I-V median prevalence was 0.9, 0.8, 0.7, 2.0 and 1.3 per 10,000, respectively (p= 0.01). Although no linear association was observed, products granted ASMR I- III (that open for premium price) had lower prevalence, than those with ASMR VI- V. Similarly, products with ASMR I-III had higher median costs: € 33,940, € 62,660, € 49,724, respectively, while those for products with ASMR IV- V were € 9,265 and € 19,757.  Conclusions: Rarity seems to be valued but does not seem to be the only parameter. Products with low and very low prevalence are associated with higher costs. This is consistent with the ASMR, as it appears to be closely correlated with the prevalence. PSY127 Comparison of Orphan Drug Market Access in A Sample of EU Countries, Ausralia, Canada and US Parviainen L1, Belgaied W2, Sediri Y2, Rémuzat C3, Toumi M4 1Creativ-Ceuticals, Rotterdam, The Netherlands, 2Creativ-Ceutical, Tunis, Tunisia, 3CreativCeuticals, Paris, France, 4Aix-Marseille University, Marseille, France

Objectives: Compare market access (MA) considerations for designated orphan drugs (DOD) in selected countries: EU5, Australia, Canada, Netherlands, Sweden, and US (United States).  Methods: Targeted literature review in MEDLINE, grey literature and health authorities’ websites, establishing DOD-specific pricing and reimbursement policies.  Results: DOD-specific policies vary greatly from country to country; regulations target either health technology assessment (HTA) process or pricing rules. In the UK, a specific framework exists for ultra-orphan drugs, applied in the highly specialised technical committee in England, and in Scotland for all ultra-orphan conditions with a substantial medical impact. In Germany, marketing authorisation is considered proof of additional benefit if revenues remain below a € 50 million/year threshold; otherwise DODs are assessed as conventional drugs. Conversely, some countries have no DOD-specific HTA processes or pricing regulations, but particular considerations are often employed. Higher cost-effectiveness thresholds in Sweden and the UK are utilized, while in France, both increased flexibility regarding the strength of evidence and exemption from economic evaluation for low budget impact products are engaged. In Australia, the Life Saving Drugs Program provides subsidised access.Furthermore, many countries have special DOD funds to support reimbursement, whilst manufacturers may provide free-access programs via patient groups. Additionally, ranges of managed entry agreements (e.g. pay-for-performance in Italy, price-volume agreement in France, discounts through patient access schemes in the UK) are used to address uncertainties regarding clinical value and high cost of DODs.  Conclusions: Initiatives to enhance MA for DODs remain ambiguous between countries; where some countries have clearly dedicated DOD pricing and reimbursement frameworks, other countries’ processes are less transparent or inexistent. Future work with relevant stakeholders is expected to establish a consistent MA approach to improve patient access. PSY128 Rare Disease Treatment Recommendations in the UK: What Limitations and Requests are Imposed as Part of Nice HST Guidance? Chotai R, Mistry J