ISSUE: Will the new wave of regenerative medicines require new funding paths, evidence evaluation approaches, and value determination methods? OVERVIEW: In 2014, there was agreement that sofosbuvir delivered a cure because there was consensus around the trial design (RCT), endpoint (sustained virological response), and effect size (96%). Regenerative medicines (RM) are different. Most cannot demonstrate curative efficacy in the typical trial setting, only “absence of disease” / “disease interruption.” Against this backdrop, regulators discuss novel endpoints (e.g., “short-term” performance) and trial designs (e.g., adaptive). In this panel, we ask what trial designs will convince payers of curative efficacy? What endpoints? What effect sizes? What real-world evidence? Moderator will summarize RM evidence and funding challenges. Panelists will debate whether there is a need for new approaches to evidence generation and evaluation, funding, and value quantification. Derek van Amerongen will argue that a “cure” must prove it is just that to justify expected financial impact. Novel designs and endpoints are likely to obscure the real outcomes. Commercial plans will struggle with huge upfront costs for these therapies, especially with membership shifts. Ulf Maywald will question whether huge upfront expenditures are justified by promised effects in the long run, especially if alternatives exist (e.g., gene therapy vs. factor substitution in hemophilia). He will ask whether we should wait for proven long-term effectiveness, and if so, whether we can explain that adequately to the insured population. Oriol Sola-Morales will argue that RM will initially bring more uncertainty, but as an increasing body of evidence develops, some new forms of surrogate evidence will be accepted by both regulators and payers. Payers will demand new regulatory arrangements and impose alternative payment systems. Stakeholders working in drug development, evidence generation, payer strategy, and payer communications will benefit from payer perspectives in three major markets.