NICE Advocates Reimbursement for Avapritinib in Aggressive Systemic Mastocytosis, Other Hematologic Malignancies

Leukemia

The United Kingdom’s National Institute for Health and Care Excellence (NICE) has issued final guidance advocating for reimbursement for the KIT D816V inhibitor avapritinib (Ayvakyt) when used as monotherapy in eligible adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), or mast cell leukemia. The recommendation is consistent with the marketing authorization the agent received from the Medicines and Healthcare products Regulatory Agency (MHRA) in September 2024.¹

Under the guidance, eligible patients in England and Wales may receive avapritinib through the National Health Service (NHS) across all lines of therapy, including in the frontline setting.

“These disease subtypes can lead to challenging, unpredictable symptoms and life-threatening complications, causing a range of physical, emotional and social impacts for those affected. We appreciate working alongside the biopharmaceutical industry, clinical experts and the patient community to improve treatment options for all those living with the disease,” Jessica Hobart, chair and trustee at The UK Mastocytosis Support Group, stated in the news release.

The MHRA and NICE assessments were mainly based on findings from the phase 2 PATHFINDER (NCT03580655) and the phase 1 EXPLORER (NCT02561988) trials. At a median follow-up of 14.3 months, data from a pooled analysis of the 2 studies demonstrated that patients who received avapritinib (n = 72) achieved an overall response rate (ORR) of 68.0% (95% CI, 56.0%-78.6%). The complete response (CR) plus CR with partial recovery of peripheral blood counts rate was 18%.

In the pooled safety population of PATHFINDER and EXPLORER (n = 126), the most common any-grade adverse effects (AEs) included periorbital edema (38%), thrombocytopenia (37%), peripheral edema (33%), and anemia (22%). Serious AEs were reported in 12% of patients and included subdural hematoma (2%), anemia (2%), and hemorrhage (2%). AEs related to cognitive effects, fluid retention, QT interval prolongation, gastrointestinal disorders, abnormal laboratory parameters, and photosensitivity reactions also occurred. AEs leading to treatment discontinuation occurred at a rate of 7.1%, and AEs led to death in less than 1% of patients.

“Traditionally, patients with ASM, SM-AHN, and mast cell leukemia have faced a poor prognosis with limited treatment options to address the life-threatening organ damage associated with the disease,” Deepti Radia, MD, a consultant hematologist at Guy’s and St Thomas’ NHS Foundation Trust, and an investigator on the PATHFINDER and EXPLORER trials, added in a news release. “In clinical studies, the majority of evaluable patients responded to treatment with avapritinib, with a subset achieving CRs with full or partial hematologic recovery. It has been gratifying to serve as an investigator on the avapritinib clinical trials for nearly a decade, and I welcome this new therapeutic option being available for eligible patients starting in the first-line treatment setting.”

PATHFINDER was an open-label, single-arm study that examined avapritinib in adult patients with ASM, SM-AHN, and mast cell leukemia.² Eligible patients needed to have an ECOG performance status of 0 to 3 and a serum tryptase level of at least 20 ng/mL. Patients received oral avapritinib continuously in 28-day cycles.

The primary end point was ORR based on modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis criteria. Secondary end points included time to response, duration of response, progression-free survival, overall survival, and safety.

The open-label, single-arm EXPLORER trial evaluated avapritinib in adult patients with advanced systemic mastocytosis and relapsed/refractory malignancies who had an ECOG performance status of 3 or less.³ Patients received oral avapritinib daily via 28-day cycles.

The coprimary end points were determining the maximum tolerated dose and recommended phase 2 dose of avapritinib, as well as safety determined by the rate of serious AEs. Secondary end points included ORR, morphologic response rate, quality of life, and change in liver and spleen volume by imaging.

“NICE’s recommendation recognizes the clinical value of avapritinib for eligible patients with ASM, SM-AHN, and mast cell leukemia, regardless of prior treatment history, and supports our continued efforts to redefine the global standard of care,” Tim Jones, general manager, UK & Ireland, and vice president, International Commercial, at Blueprint Medicines, said in the news release.¹

References

1. NICE recommends Blueprint Medicines’ Ayvakyt (avapritinib) for the treatment of adult patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated haematological neoplasm or mast cell leukaemia. News release. Blueprint Medicines. November 6, 2024. Accessed November 6, 2024.
2. (PATHFINDER) study to evaluate efficacy and safety of avapritinib (BLU-285), a selective KIT mutation-targeted Tyrosine kinase inhibitor, in patients with advanced systemic mastocytosis. ClinicalTrials.gov. Updated August 7, 2024. Accessed November 6, 2024. https://clinicaltrials.gov/study/NCT03580655
3. (EXPLORER) study of BLU-285 in patients with advanced systemic mastocytosis (AdvSM) and relapsed or refractory myeloid malignancies. Updated March 17, 2023. Accessed November 6, 2024. https://clinicaltrials.gov/study/NCT02561988