Analysis Group Announces Study Using Real-World Evidence to Support Blueprint Medicines’ AYVAKYT® (avapritinib) Label Expansion for Advanced Systemic Mastocytosis in Europe

Date:August 17, 2022
Location:Boston, MA

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.   

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.”

Analysis Group’s rigorous, retrospective analyses showed that AYVAKYT improved overall survival, extended duration of treatment, and reduced mast cell burden in patients with AdvSM when indirectly compared to real-world data from best available therapies. In these analyses, patients treated with AYVAKYT had a 41% reduction in the risk of death compared to patients treated with midostaurin and a 68% reduction in the risk of death compared to patients treated with cladribine.

AYVAKYT is designed to selectively target the KIT D816V mutation, the primary driver of AdvSM. The EMA’s regulatory approval extends the treatment’s use in the European Union (EU) as a monotherapy for the treatment of adult patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated haematological neoplasm or mast cell leukaemia, after at least one systemic therapy.

Results from the study, “Efficacy of Avapritinib Versus Best Available Therapy in the Treatment of Advanced Systemic Mastocytosis” were published in July by Leukemia. The study’s findings were also presented during June’s European Hematology Association (EHA) 2022 Congress.

In addition to Dr. Duh and Dr. Bobbili, investigators included Dr. Andreas Reiter of University Hospital Mannheim; Dr. Daniel J. DeAngelo of the Dana-Farber Cancer Institute and Harvard Medical School; Dr. Jason R. Gotlib of Stanford Cancer Institute and Stanford University School of Medicine; Dr. Iván Álvarez-Twose of the Institute of Mastocytosis Studies of Castilla La Mancha, Virgen del Valle Hospital; Dr. Peter Valent of the Division of Hematology and Hemostaseology, Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna; Dr. Deepti H. Radia of Guy’s & St Thomas’ NHS Foundation Trust of Guy’s Hospital; Blueprint Medicines’ Chelsea Norregaard, Dr. Saša Dimitrijevic, Dr. Erin Sullivan, and Dr. Melinda Louie-Gao; and Analysis Group Manager Dr. Aolin Wang and Senior Analyst Selvam Sendhil.


Blueprint Medicines, AYVAKYT, and associated logos are trademarks of Blueprint Medicines Corporation.

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About Analysis Group’s HEOR Practice

Founded in 1981, Analysis Group is one of the largest international economics consulting firms, with more than 1,000 professionals across 14 offices. Analysis Group’s health care experts apply analytical expertise to health economics and outcomes research, clinical research, drug safety, epidemiology, market access and commercial strategy, and health care policy. Analysis Group’s internal experts, together with its network of affiliated experts from academia, industry, and government, provide our clients with exceptional breadth and depth of expertise and end-to-end consulting services globally.