Drug budget and prescription control measures are implemented regionally in Germany, meaning that the uptake of pharmaceuticals, including biosimilars, can vary by region. We examine regional market dynamics of tumor necrosis factor alpha (TNFα) inhibitor originators and biosimilars in Germany and studied the influence of biosimilar policies on these dynamics. This study is based on: (1) a literature review in which German biosimilar policies are identified, (2) the analysis of dispensing data (2010–2018) for the class of TNFα inhibitors, and (3) ten semi-structured interviews investigating prescribers’ and insurers’ views on factors potentially influencing biosimilar uptake. The analysis of biosimilar market shares of infliximab and etanercept revealed wide variations across the 17 German Regional Associations of Statutory Health Insurance Accredited Physicians (PA regions). Quantitative analyses indicated that biosimilar market shares for infliximab and etanercept were significantly lower in former East Germany when compared to former West Germany regions. Through qualitative interview analyses, this study showed that the use of infliximab and etanercept biosimilars across Germany is primarily influenced by (1) the regional-level implementation of biosimilar quotas and the presence of monitoring/sanctioning mechanisms to ensure adherence to these quotas, (2) the different insurer-manufacturer discount contracts, and (3) gainsharing arrangements established at the insurer-prescriber level.

Background To encourage the rational prescribing of biologics, payers across Europe have experimented with the implementation of benefit-sharing programs. Benefit-sharing programs are incentive programs that promote the use of 'best-value' off-patent biologics and biosimilars by driving changes in prescribing practices. The aim of these programs is to generate savings that can be shared among stakeholders involved (e.g. health authorities/payers, health care professionals, hospital managers/administration) and are generally used to improve the quality of health care and to increase patients' access to innovative services and medicines. However, the scarcity of information concerning the design, implementation and outcomes of benefit-sharing programs limits the transfer of knowledge to institutions aiming to adopt these types of incentive schemes in the future. Objective The aim of our study was to map benefit-sharing experiences across Europe, to compare their design and implementation characteristics and to assess the impact of the different benefit-sharing strategies on the use of 'best-value' biologics. Method Our approach was based on a literature review and on semi-structured interviews with payers/insurers, regulators, health care professionals and industry representatives. Results Our analysis revealed variable design characteristics for benefit-sharing programs, depending on the organization of the health care system, the specific timeframe, the care setting and the policy environment. All these aspects can influence the robustness of benefit-sharing initiatives and their potential to stay in effect over time. We also noted a generalized lack of transparency regarding the distribution of savings and how they are reinvested. This lack of transparency has raised questions on how to optimally implement benefit-sharing in the future. Conclusions To realize the full potential of benefit-sharing programs, we identify the importance of (i) setting up and timely monitoring success indicators for these programs; (ii) including quality of care and access to care parameters as success indicators; (iii) establishing clear pathways for the transparent redistribution/reinvestment of savings and (iv) transparently communicating with patients about the outcomes of benefit-sharing programs.

Background: Nusinersen is an orphan drug intended for the treatment of spinal muscular atrophy (SMA), a severe genetic neuromuscular disorder. Considering the very high costs of orphan drugs and the expected market entry of cell and gene therapies, there is increased interest in the use of health technology assessment (HTA) for orphan drugs. This study explores the role of the economic evaluation and budget impact analysis on the reimbursement of nusinersen.Methods: Appraisal reports for nusinersen were retrieved from reimbursement and HTA agencies in Belgium, Canada, France, England and Wales, Germany, Italy, Ireland, Scotland, Sweden, the Netherlands, and the United States. Detailed information was extracted on the economic evaluation, the budget impact, the overall reimbursement decision, and the managed entry agreement (MEA). Costs were adjusted for inflation and currency.Results: Overall, the reports included limited data on budget impact, excluding information on the sources of data for cost and patient estimates. Only three jurisdictions reported on total budget impact, estimated between 30 and 40 million euros per year. For early-onset SMA, the incremental cost-effectiveness threshold (ICER) ranged from €464,891 to €6,399,097 per quality-adjusted life year (QALY) gained for nusinersen versus standard of care. For later-onset SMA, the ICER varied from €493,756 to €10,611,936 per QALY. Although none of the jurisdictions found nusinersen to be cost-effective, reimbursement was granted in each jurisdiction. Remarkably, only four reports included arguments in favor of reimbursement. However, the majority of the jurisdictions set up an MEA, which may have promoted a positive reimbursement decision.Conclusion: There is a need for more transparency on the appraisal process and conditions included in the MEA. Additionally, by considering all relevant criteria explicitly during the appraisal process, decision-makers are in a better position to justify their allocation of funds among the rising number of orphan drugs that are coming to the market in the near future.

Background: Countries are struggling to provide affordable access to medicines while supporting the market entry of innovative, expensive products. This Perspective aims to discuss challenges and avenues for balancing health care system objectives of access, affordability and innovation related to medicines in Belgium (and in other countries).Methods: This Perspective focuses on the R&D, regulatory approval and market access phases, with particular attention to oncology medicines, precision medicines, orphan medicines, advanced therapies, repurposed medicines, generics and biosimilars. The authors conducted a narrative review of the peer-reviewed literature, of the grey literature (such as policy documents and reports of consultancy agencies), and of their own research.Results: Health care stakeholders need to consider various initiatives for balancing innovation with access to medicines, which relate to clinical and non-clinical outcomes (e.g. supporting the conduct of pragmatic clinical trials, treatment optimisation and patient preference studies, optimising the use of real-world evidence in market access decision making), value assessment (e.g. increasing the transparency of the reimbursement system and criteria, tailoring the design of managed entry agreements to specific types of uncertainty), affordability (e.g. harnessing the role of generics and biosimilars in encouraging price competition, maximising opportunities for personalising and repurposing medicines) and access mechanisms (e.g. promoting collaboration and early dialogue between stakeholders including patients). Conclusion:Although there is no silver bullet that can balance valuable innovation with affordable access to medicines, (Belgian) policy and decision makers should continue to explore initiatives that exploit the potential of both the on-patent and off-patent pharmaceutical markets.

Background: The level of competition achieved following biosimilars market availability varies by country, care setting and molecule. Hence, biosimilars contribution to attaining price reductions and extended access to treatments can also vary.Objective: The aim of this study is to capture market dynamics for tumor necrosis factor (TNF)-alpha inhibitors and competing molecules in Southern European markets (2011–2020), and to evaluate the benefits of the competition generated by the availability of biosimilars.Methods: This study is based on a literature review examining market characteristics for TNF-alfa inhibitors and competing immunomodulator molecules, and on the quantitative analysis of market data for these molecules in Italy, Portugal and Spain.Results: Following biosimilars availability in Italian, Portuguese and Spanish markets, there has been an expansion in the overall access to TNF-alfa inhibitor pharmaceuticals. Further, savings have been generated within the TNF-alfa inhibitors class even after the increased use of these molecules. However, the potential of infliximab, etanercept and adalimumab biosimilars to generate price competition outside of their own drug class appeared limited in the studied markets. Considering this limitation and that shifts towards on-patent and higher-cost therapies have occurred after TNF-alfa inhibitor biosimilars availability, the importance of investing in biosimilars development for still on-patent immunology biologics is emphasized.Conclusion: This study highlights the need for policies that do not only seek higher utilization of biosimilars, but that also support a sustainable market for these products. This is expected to foster the future development of biosimilar medicines.