Orphan Drugs In France: Key Market Access Incentives

VA L U E I N H E A LT H

current study aimed at identifying preferences of the French general population regarding a number of determinants in a discrete choice experiment.  Methods: The list of attributes was formed based on a literature search and was refined through expert interviews, a focus group, and a pilot study. The final list included nine attributes: disease disability and mortality, number of patients, availability of alternative treatments, treatment impact on disease disability and survival, treatment safety, uncertainty around therapeutic effect, and annual treatment cost per patient. Participants were presented with 12 questions containing two drugs profiles described according to the attributes and were asked to choose one (or none) treatment. The questionnaire was distributed using a web platform. A conditional logit model was used for statistical analyses and included all attributes and a dummy variable corresponding to a choice of none treatment. An interaction between the number of patients and per patient cost was tested.  Results: A total of 958 persons participated in the study. The highest estimate weight was observed for treatment impact (p< 0.0001) on survival and uncertainty around therapeutic effect (p< 0.0001). Participants were also sensitive to the availability of alternative treatments (p= 0.0014), treatment safety (p< 0.0001) and impact on disability (p= 0.0001), disease mortality (p< 0.0001) . Participant preferred more prevalent diseases (p< 0.0001). Although the interaction between the number of patients and per patient cost was significant (p< 0.0001), the trend in preferences toward lower per patient costs was not observed.  Conclusions: The society does not seem to support drugs for less prevalent diseases and to be aware about drug pricing in general. Should special measures for orphan drugs be introduced, education on their necessity is needed. PSY116 Orphan Drugs In France: Key Market Access Incentives Mennezein L1, Avot D1, Laigle V2 1MSD France, Courbevoie, France, 2MSD Vaccins, Lyon, France

Objectives: In Europe, an orphan disease is defined by a prevalence of less than 5 in 10 000 inhabitants which represent a maximum target population of 30 000 patients in France. Economic incentives are set up by authorities to encourage pharmaceutical development in rare disease treatments. This analysis aims at exploring French stakeholders’ policy toward orphan drugs on both Transparency Committee (TC) assessment and pricing decisions.  Methods: All non-oncologic orphan drugs listed between 2006 and 2016 were identified. TC opinion (study design, comparator, target population) and price evolution were analyzed for each drug. First, results were compared to data for all drugs assessed in 2015, when available. Then, orphan drugs were clustered in two periods of time (2006-2010 and 2011-2016) in order to describe variations on assessment and price lifecycle.  Results: 53 orphan drugs were analyzed on two main items: HTA assessment and price evolution. 40% of orphan drugs received an ASMR I to III (high to moderate improved clinical benefit) from TC from 2006 to 2016 versus 3% among drugs of all types (2015). From 2006 to 2010, the rate of ASMR I to III among orphan drugs reached 57% versus 29% between 2011 and 2016. Application process time for orphan drugs from publication of TC opinion to price release is similar between the two periods. First price reduction for orphan drugs occurred in average 4.7 years after price release regardless of ASMR level. In general, 5 years price stability is known to be granted only for products with ASMR I to III.  Conclusions: In France, orphan drugs seem to benefit from a more favorable market access vis-a-vis drugs of all types regarding price evolution and HTA assessment. However, a strengthening of TC doctrine seems to emerge in the 5 past years despite similar level of demonstration. PSY117 Critical Assessment Of Atmp Market Access Outcomes On A National-Level Across EU5 Countries Jones-Phillips DL, Bradshaw SE Valid Insight, London, UK

Objectives: Advanced therapy medical products (ATMPs) pose specific pricing, reimbursement and market access considerations. The aim of this research is to review ATMP assessments by EU HTA bodies to understand key drivers for securing adoption.  Methods: HTA websites from France (HAS), Germany (IQWiG/G-BA), Italy (AIFA and regions), Spain (MSSSI and regions) and the UK (NICE, SMC) were searched. Targeted reviews of journal publications, policy documents and grey literature were also performed.  Results: Provenge was withdrawn from the EU in May 2015, ChondroCelect in 2016 and Glybera is due to be withdrawn in October 2017. At HTA-level, in Germany, Glybera, Holoclar, Imlygic and Strimvelis all went through the AMNOG process. Glybera gained an ‘unquantifiable benefit’ outcome as submitted clinical data were not supportive of medical benefit. Reimbursement was later gained through insurers following reclassification to a tissue engineered product (TEP), putting Glybera outside of the AMNOG process. Imlygic obtained an ‘unquantifiable’ outcome as the G-BA considered the choice of comparator (GM-CSF) to be wrong. Strimvelis is still being assessed. ChondroCelect, Glybera and Holoclar were assessed by HAS; ChondroCelect was rejected because of a lack of demonstrated efficacy in clinically recognized trial outcomes. Glybera was awarded an ‘insufficient’ ASMR because of uncertainties around short to medium term safety, and the inability to re-administer after initial treatment. Holoclar achieved an ASMR IV for minor added benefit in a condition with high unmet need.  Conclusions: Comments from HAS on the lack of recognizable clinical outcomes, and reclassification of Glybera in Germany to a TEP, demonstrates that national HTA process are not yet adapted to the early clinical datasets and novel outcome measures that ATMPs utilise. These products require new approaches to assessing value, and so strong value stories that educate on ATMPs being the solution for burdensome conditions, will be key to future success. PSY118 The Multicriteria Decision Analysis Of Using Tetrabenazine For Patients With Hungtington’s Disease In Russia Krysanova V1, Krysanov I2, Ermakova V1 University, Moscow, Russia, 2Institute of Medical and Social Technologies, Moscow National University of Food Production, Moscow, Russia

1Sechenov

20 (2017) A399–A811

A565

Objectives: Orphan diseases such as Huntington’s disease (HD), a progressive neurodegenerative disorder, have significant impact on patients and their families, as well as the healthcare systems and societies. The main aim of this study was to perform multicriteria decision analysis (MCDA) to evaluate various aspects of a medicament providing of tetrabenazine (TBZ) for patients with HD.  Methods: Analysis of the published clinical trials was conducted to evaluate efficacy and safety of using TBZ for patients with HD. The initial list of value attributes (5 - impact of rare disease and 5 - impact of the drug) was identified from a literature review and expert’s survey. Further experts assigned relative weights to the attributes in 2 groups (the rating scale ranged from 1(less important) to 5 (most importantly)). Then experts rated TBZ against each attribute (the rating scale ranged from 1 (worst score) to 7 (best score)). In the end weighted score for each attribute was identified.  Results: Experts considered that the most important attributes are the impact of disease (scores 27.3 versus 24.7). In the both groups the most important attribute was evidence of treatment clinical efficacy and patient clinical outcome (scores 6.67 and 6.00). A total weighted score for attributes of the disease was 85.78, and for attributes of the impact of the drug – 78.67.  Conclusions: All experts agreed to give slightly more weight to the attributes of the disease than to the impact of the drug. The present study was the first experience of conducting MCDA for HD. This analysis showed the importance of the different kinds of aspects in deciding on funding drug supply patients with HD. PSY119 Transition From Orphan Disease To Full Assessment In The German Amnog System: Key Learnings From Pioneers Templin C, Erwes KL, Italia N, Kulp W Xcenda GmbH, Hannover, Germany

Objectives: A specific feature of the German HTA process is the relevance of the orphan disease (OD) status. The additional medical benefit of orphan drugs, assessed by the German HTA body (G-BA, Federal Joint Committee) is already acknowledged by approval. Companies are not obliged to present head-to-head data against an appropriate comparator. However, if the revenue per annum exceeds 50 million euros or OD status is lost, reevaluation against an appropriate comparator is mandatory. The aim of this study is to reveal the consequences of reevaluation with regard to acceptance of study data, patient relevant endpoints and extent of additional benefit assigned by G-BA and IQWiG (Institute for Quality and Efficiency in Health Care), respectively.  Methods: A database containing all assessed AMNOG dossiers was screened for dossiers which have been assessed both under orphan and nonorphan conditions. Data on indication, size of target population, the comparator utilized in the company’s dossier, and outcome (added benefit) were collected and analyzed.  Results: Since 2011, five former OD drugs were reassessed: ruxolitinib (hematology), pomalidomid, ibrutinib, ramucirumab (oncology), and macitentan (cardiovascular disorders). In four cases, annual revenues had exceeded 50 million euros, and one drug was deprived of the OD designation (ramucirumab). Time between reevaluation ranged from 14 months (ibrutinib) to 32.5 months (macicentan). At initial assessment all drugs obtained an added benefit. After full evaluation four of the five compounds retained an added benefit at least in parts of the population.  Conclusions: The transition from the assessment under OD to non-OD conditions pose a major challenge for companies as the existence of an added medical benefit is no longer preconditioned. Especially since clinical evidence for orphan diseases is limited, companies launching drugs likely to exceed the revenue limit or with uncertain OD status should be aware of the strict assessment criteria for non-orphan drugs. PSY120 Market Share And Switching Dynamics Between Etanercept And Its Biosimilar Product In Sweden And Germany: A Real-World Preliminary Analysis Alten R1, Neregård P2, Jones HE3, Meng T4, Curiale C5, Singh E6, Lucchese L7, Gossen N8, Bergman GJ9, Miglio C7 1Shlosspark-Klinik Teaching Hospital of the Charité, Berlin, Germany, 2Pfizer, Sollentuna, Sweden, 3Pfizer inc., Collegeville, PA, USA, 4Pfizer Pharma GmbH, Berlin, Germany, 5Pfizer, Rome, Italy, 6Pfizer Inc., Collegeville, PA, USA, 7QuintilesIMS, London, UK, 8QuintilesIMS, Frankfurt, Germany, 9QuintilesIMS, Solna, Sweden

Objectives: To describe the market share and switching dynamics between etanercept innovator (EtnI) and its biosimilar (EtnBS) indicated for rheumatic diseases, in Germany and Sweden.  Methods: Patients receiving rheumatologists’ prescriptions for EtnI and EtnBS in November 2015-March 217 were retrospectively identified using the Swedish Prescription Registry (100% of retail biologic prescriptions) and the QuintilesIMS® German Longitudinal Prescriptions database (LRx, 60% of the German statutory health insurance market). In each country, the monthly proportion of patients on EtnI and EtnBS was recorded. In addition, the monthly proportion of naïve patients and of those switching to EtnBS from prior EtnI or other biologic treatment were evaluated (12-month lookback period), along with the proportion of patients who switched back to EtnI or other biologics after starting EtnBS.  Results: Both in Germany and Sweden, the market share of EtnI constantly decreased and that of EtnBS constantly increased after EtnBS was launched. In the month of launch (Germany: February 2016; Sweden: April 2016), the proportion of patients who switched to EtnBS from any biologic treatment was ~100% in Germany and only 22% in Sweden. In the most recent 6 months, this proportion ranged from 41% to 49% in Germany and from 61% to 72% in Sweden. In both countries there was a similar proportion of patients with prior EtnI who switched back to the original EtnI (10% in Germany and 11% in Sweden) or any biologic agents (14% in both countries) after only 75 (Germany) and 55 (Sweden) days of treatment with EtnBS.  Conclusions: Despite the observed differences in market penetration, we found that both in Germany and Sweden there is a proportion of patients who switch back to the original biologic agent after being moved to EtnBS. Future studies should confirm these results and investigate the reasons for changing back to original biologics.