Analysis Group, a global leader in health economics and outcomes research (HEOR) and regulatory epidemiology, announced that a study it coauthored helped support Blueprint Medicines’ label expansion of AYVAKYT (avapritinib) to include monotherapy for the treatment of adult patients with advanced systemic mastocytosis (AdvSM), after at least one systemic therapy, in Europe. The real-world evidence (RWE) generated by the study provided an external control arm to help the European Medicines Agency (EMA) interpret single-arm Phase 1 EXPLORER and Phase 2 PATHFINDER trial findings. AdvSM is a rare blood disease characterized by damage across multiple organ systems, reduced overall survival, and poor quality of life.
Also Read: Preparing for Continuing Battle with COVID, MicroGEM Partners with Medline
The EMA’s acceptance of RWE in regulatory decision making has steadily increased since its Operational, Technical, and Methodological (OPTIMAL) framework was published in 2019. However, few studies have demonstrated sufficient evidentiary value of RWE for treatment outcomes. Researchers from Analysis Group and Blueprint Medicines collaborated with several renowned investigators from Europe and the US to design an observational retrospective cohort study that involved chart review of real-world clinical data on best available therapies from six sites – four European and two US – to identify real-world patients whose eligibility criteria were similar to patients enrolled in the EXPLORER and PATHFINDER trials of AYVAKYT.
“RWE as an external control is a valuable tool for both regulators and clinical decision-makers, particularly in instances of rare diseases with high unmet needs like AdvSM. A control that is well-matched to the single-arm trial, coupled with robust statistical adjustment methods, provides useful indirect treatment comparisons,” said study co-investigator Dr. Mei Sheng Duh, a Managing Principal at Analysis Group. “In its European public assessment report [EPAR], the EMA took the rare step of highlighting the study’s results, absent a randomized controlled trial. The report noted that the RWE provided valuable insights into the efficacy of AYVAKYT, supporting the successful label expansion.”
“From the start, the goal was to draw as tight a parallel as possible between the real-world and clinical trial patient populations,” noted Dr. Priyanka Bobbili, a Manager at Analysis Group and a co-investigator. “We chose qualified centers of excellence for treating AdvSM to ensure the highest-quality data were being collected and accurately classified. These exceptional data fed the rigorous statistical analyses of inverse probability of treatment weighting that we employed to indirectly compare real-world and trial outcomes.”