Access to innovative medicines for metastatic melanoma worldwide: Melanoma World Society and European Association of Dermato-oncology survey in 34 countries

Highlights

• New therapies have dramatically improved the prognosis of metastatic melanoma, but disparities in access to these medicines exist worldwide.

• BRAFi+MEKi combinations are fully reimbursed in 17 of 34 (50%) countries.

• Anti-PD1 immunotherapies are fully reimbursed in 17 of 34 (50%) countries.

• Combination immunotherapy (anti-CTLA4+anti-PD1) is reimbursed in 9 of 34 (26.4%) countries, in 3 countries with restrictions.

• Patient-oriented research, development, market access and reimbursement mechanisms must be urgently developed.

Abstract

According to data from recent studies from Europe, a large percentage of patients have restricted access to innovative medicines for metastatic melanoma. Melanoma World Society and European Association of Dermato-oncology conducted a Web-based survey on access to first-line recommended treatments for metastatic melanoma by current guidelines (National Comprehensive Center Network, European Society for Medical Oncology [ESMO] and European Organization for Research and Treatment of Cancer/European Association of Dermato-oncology/European dermatology Forum) among melanoma experts from 27 European countries, USA, China, Australia, Argentina, Brazil, Chile and Mexico from September 1st, 2017 to July 1st, 2018. Data on licencing and reimbursement of medicines and the number of patient treated were correlated with the data on health expenditure per capita (HEPC), Mackenbach score of health policy performance, health technology assessment (HTA), ASCO and ESMO Magnitude of clinical benefit scale (ESMO MCBS) scores of clinical benefit and market price of medicines. Regression analysis for evaluation of correlation between the parameters was carried out using SPSS software. The estimated number of patients without access in surveyed countries was 13768. The recommended BRAFi + MEKi combination and anti-PD1 immunotherapy were fully reimbursed/covered in 19 of 34 (55.8%) and 17 of 34 (50%) countries, and combination anti-CTLA4+anti-PD1 in was fully covered in 6 of 34 (17.6%) countries. Median delay in reimbursement was 991 days, and it was in significant correlation with ESMO MCBS (p = 0.02), median market price (p = 0.001), HEPC and Mackenbach scores (p < 0.01). Price negotiations or managed entry agreements (MEAs) with national authorities were necessary for reimbursement. In conclusion, great discrepancy exists in metastatic melanoma treatment globally. Access to innovative medicines is in correlation with economic parameters as well as with healthcare system performance parameters. Patient-oriented drug development, market access and reimbursement pathways must be urgently found.

Introduction

Metastatic melanoma is a chemotherapy-resistant cancer with an expected median survival of 6–9 months before 2010. From 2011, major breakthrough was achieved with targeted therapy and immunotherapy, leading for the first time to significantly prolonged survival of this group of patients, with 28–34% of patients (nearly 50% in good prognostic groups) surviving 5 years based on the recent trials [1], [2], [3], [4], [5], [6], [7], [8], [9]. However, despite the high efficacy, their high costs have led to the restricted access to these treatments in parts of Europe [10], [11], [12], [13], [14], [15].

Most innovative medicines are authorised first by the Food and Drug Administration (FDA) in the United States and subsequently in the European Union by the European Medicine Agency (EMA), typically with a delay of 6–12 months. However, the degree and timing of reimbursement in every European country is decided at the national level, and it varies greatly [15], [16], [17], [18], [19]. In the United States and in other countries with existing private insurance, availability of the medicines is also dependent on patients' insurance coverage [20], [21], [22]. Delays in reimbursement and different insurance coverage lead to different and rising out-of-pocket costs for the patient, indicating the challenges for healthcare systems in adapting to the rising costs of cancer care [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22].

In this setting, there is a need for objective measurement of clinical benefit of every treatment and development of value-based pricing [23], [24], [25]. The major oncology organisations, American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO), developed scores of clinical benefit, ASCO Framework net clinical benefit 16 score (NBS 16) and ESMO Magnitude of clinical benefit score (MCBS), with an intention to be used for development of value-based pricing and prioritisation of medicines for reimbursement and/or insurance coverage [24], [25].

The degree of inequality and major determinants of access to innovative treatments for metastatic melanoma are largely unexplored. Thus, the Melanoma World Society (MWS) and the European Association of Dermato-oncology (EADO) conducted a survey on access to first-line recommended treatments per current guidelines (National Comprehensive Center Network [NCCN], ESMO, European Organization for Research and Treatment of Cancer [EORTC]/EADO/European dermatology Forum [EDF]) in 34 countries worldwide and updated the results of European survey conducted in 2016. To further explore the patterns of access to innovative medicines for metastatic melanoma, data on access were correlated with their score of clinical benefit, i.e. ASCO NBS and ESMO MCBS, as well as economic parameters and parameters of health policy performance.