Ayvakit data showed high, durable response rates and prolonged overall survival (OS) in patients with advanced systemic mastocytosis

The findings are being reported in two presentations, including an oral presentation featuring updated follow-up from treatment-naïve patients in the PATHFINDER trial, at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition in New Orleans.

Ayvakit is approved by the FDA for the treatment of adults with Advanced SM. SM is a rare hematologic disorder driven by the KIT D816V mutation in approximately 95 percent of cases. In advanced SM, the median OS has ranged from less than six months to approximately 3.5 years, depending on the subtype.1 Ayvakit was designed to potently and selectively inhibit D816V mutant KIT.

"Ayvakit has demonstrated significant clinical benefits in patients with advanced systemic mastocytosis, including complete remissions and durable responses that have translated into a highly meaningful impact on overall survival," said Deepti Radia, M.D., a hematologist and an investigator on the PATHFINDER and EXPLORER trials. "As a physician specializing in SM and other myeloproliferative neoplasms, I am encouraged that treatment-naïve patients with SM-AHN had a 95 percent response rate and an estimated two-year survival rate of 86 percent in the PATHFINDER trial. Before the introduction of KIT D816V-targeted therapy, physicians often focused on treating the AHN component of SM-AHN. Ayvakit represents a practice-changing advancement for this patient population, and updated PATHFINDER data highlight the importance of treating the SM for early therapeutic intervention in SM-AHN patients with measurable 'C' findings, excluding those with aggressive AHNs."

Ayvakit – Updated data from the PATHFINDER and EXPLORER trials in advanced SM: Long-term follow-up of 38 treatment-naïve patients from the PATHFINDER trial and 69 patients from the EXPLORER trial – regardless of line of therapy – further validate the clinical efficacy and safety profile of Ayvakit in advanced SM. Based on modified IWG-MRT-ECNM criteria, the overall response rate (ORR) was defined as complete remission with full or partial recovery of peripheral blood counts (CR/CRh), partial remission or clinical improvement. All responses were confirmed. In the PATHFINDER trial, Ayvakit showed broad clinical activity in treatment-naïve patients evaluable for response (n=25), including those with SM-AHN (n=19), as of a data cutoff date of April 20, 2021.

For treatment-naïve patients across advanced SM subtypes: i. ORR was 84 percent and CR/CRh rate was 32 percent. ii. Median time to response was two months and median time to CR/CRh was six months. iii. Median duration of response (DOR) has not been reached. iv.Estimated 24-month OS rate was 88 percent.

For treatment-naïve patients with SM-AHN: i. ORR was 95 percent and CR/CRh rate was 37 percent. ii. Estimated 24-month OS rate was 86 percent. iii. In addition, improvements were observed across hematologic parameters, such as monocytes and eosinophils in the peripheral blood, suggesting multi-lineage involvement of the KIT D816V mutation.

In the EXPLORER trial, 57 patients across lines of therapy were evaluable for response as of a data cutoff date of April 5, 2022. The ORR was 77 percent, with median DOR and OS not reached in patients followed for up for six years.

Safety data from the PATHFINDER and EXPLORER trials were consistent with previously reported results and the FDA approved labeling for Ayvakit, and reinforce the favorable benefit-risk profile of Ayvakit at the 200 mg once-daily (QD) recommended dose. The most common treatment-related adverse events (AEs) included periorbital edema, thrombocytopenia, peripheral edema, anemia and nausea. Discontinuations due to treatment-related AEs occurred in four treatment-naïve patients (11 percent) since the initiation of the PATHFINDER trial in 2018, and seven patients across lines of therapy (10 percent) since the initiation of the EXPLORER trial in 2016.