Continued progress presented at AHA congress of Ayvakit toward transforming treatment of systemic mastocytosis.

Findings showed Ayvakit improved overall survival (OS), as well as other clinical outcomes, in patients with advanced SM, when indirectly compared to real-world data for prior best available therapies. Based on these analyses, patients treated with Ayvakit had a 41 percent reduction in the risk of death compared to patients treated with midostaurin and a 68 percent reduction in the risk of death compared to patients treated with cladribine. In total, Blueprint Medicines is supporting the presentation of seven abstracts at the EHA 2022 Congress, highlighting the company's leadership in SM.

In addition, Blueprint Medicines plans to update the primary endpoint of the registrational PIONEER trial of Ayvakit in patients with non-advanced SM, based on a written recommendation from the FDA on statistical considerations ahead of the planned database lock. The mean absolute change in total symptom score (TSS), previously a key secondary endpoint, will be the primary endpoint and the proportion of patients with a 30 percent or greater decrease in TSS, previously the primary endpoint, will be a key secondary endpoint. Both analyses were previously defined as key endpoints that the PIONEER trial was powered to assess. In addition, both endpoints are based on the Indolent SM Symptom Assessment Form, a patient-reported outcomes tool that has been developed and validated in collaboration with the SM community and global regulatory authorities.

Blueprint Medicines continues to plan to report top-line data from the PIONEER trial in late summer 2022 and submit a supplemental new drug application to the FDA for Ayvakit for non-advanced SM by the end of 2022.

Highlights from Ayvakit Presentations at the EHA 2022 Congress: Three presentations at the EHA 2022 Congress will highlight results from a study (NCT04695431) indirectly comparing clinical outcomes in advanced SM patients receiving Ayvakit in the registrational EXPLORER and PATHFINDER trials, versus patients treated with best available therapy in real-world clinical practice. Results showed that Ayvakit improved clinical outcomes when retrospectively compared to best available therapies, including the two other most common treatments (midostaurin, cladribine) identified in the real-world study cohort.

For the study, patients treated in real-world clinical practice were identified in a retrospective medical chart review at six centers with similar patient eligibility criteria as EXPLORER and PATHFINDER. Retrospective data were collected and analyzed using methods to balance key baseline variables; however, the study may have limitations due to inherent differences between data collected from prospective trials and real-world experience. No prospective, randomized, controlled head-to-head studies have been conducted comparing Ayvakit to other therapies in patients with advanced SM. EXPLORER and PATHFINDER results were reported as of an April 20, 2021 cutoff date.

Weighted, indirect comparison analyses showed: i Ayvakit (all doses) reduced the risk of death by 58 percent compared to best available therapy (p<0.001) in patients with sm with an associated hematological neoplasm (sm-ahn). ii. ayvakit (200 mg once-daily dose) reduced the risk of treatment discontinuation by 64 percent compared to best available therapy (p><0.001) in advanced sm patients. iii. the maximum percent reduction in serum tryptase levels for ayvakit (200 mg once-daily dose) was 85 percent, compared to 9 percent for best available therapy (p><0.001), in advanced sm patients.

Regulatory approvals in the U.S. and EU were based on results from the EXPLORER and PATHFINDER trials.