December 1, 2023

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First precision treatment for systemic mastocytosis (SM): Ayvakit (Avatinib)

First precision treatment for systemic mastocytosis (SM): Ayvakit (Avatinib)! The U.S. FDA approved the KIT inhibitor Ayvakit (Avatinib)


First precision treatment for systemic mastocytosis (SM): Ayvakit (Avatinib).  Blueprint Medicines recently announced that the US Food and Drug Administration (FDA) has approved a new indication for the targeted anticancer drug Ayvakit (avapritinib) for the treatment of adults with advanced systemic mastocytosis (SM) Patients, including: aggressive SM (ASM), SM with related hematological tumors (SM-AHN) and mast cell leukemia (MCL).

First precision treatment for systemic mastocytosis (SM): Ayvakit (Avatinib)

Systemic mastocytosis-SM (Image source:


This indication was approved through a priority review process. Previously, the FDA has granted Ayvakit Orphan Drug Designation (ODD) and Breakthrough Drug Designation (BTD) for the treatment of advanced SM.

It is worth mentioning that Ayvakit is the first precision therapy aimed at the main driving factors of SM disease. The approval of this drug on the market provides the first targeted therapy for advanced SM patients. Ayvakit can potently and selectively inhibit the D816V mutation KIT, which is the central driving factor of SM disease. In terms of medication, the recommended dose of Ayvakit for patients with advanced SM is 200 mg orally once a day. For patients with advanced SM with a platelet count less than 50 X 10E9/L, Ayvakit is not recommended.

SM is a rare and debilitating blood disease. Almost all cases are caused by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells can lead to life-threatening complications. Among the advanced SM subtypes, the median overall survival (OS) of ASM patients is about 3.5 years, the median OS of SM-AHN patients is about 2 years, and the median OS of MCL patients is less than 6 months. Prior to Ayvakit, there was no approved treatment that could selectively inhibit the KIT D816V mutation. The multi-kinase inhibitor midostaurin has been approved for the treatment of advanced SM. According to the IWG standard, the ORR is 28%.

Ayvakit is a precision therapy for SM, and it is the only highly potent KIT D816V inhibitor that has been clinically proven in SM. The strong efficacy and safety data from two clinical trials EXPLORER (NCT02561988) and PATHFINDER (NCT03580655) support the full approval of Ayvakit for the treatment of advanced SM. Both of these two trials are multi-center, single-arm, open-label trials. A total of 53 patients received Ayvakit once a day treatment, including those who had previously received treatment or had not been treated. The primary endpoints are the overall response rate (ORR) and duration of response (DOR) determined according to the modified IWG-MRT-ECNM criteria (IWG criteria).

The data showed that among all evaluable patients (n=53) in the 2 trials, Ayvakit treatment showed a high response rate, with an ORR of 57% (95%CI: 42-70), a complete response rate (CR) of 28%, and partial The remission rate (PR) was 28%. Ayvakit treatment showed rapid and lasting remission, with a median DOR of 38.3 months (95%CI: 19-NE), and a median time from treatment to response of 2.1 months. The most common adverse reactions (incidence ≥20%) are edema, diarrhea, nausea, fatigue/asthenia.

In June 2018, CStone Pharmaceuticals reached an exclusive cooperation and licensing agreement with Blueprint Medicines, and obtained avapritinib (avapritinib, a potent KIT/PDGFRA kinase inhibitor), pralsetinib (pratinib, a potent RET inhibitor) ), including the development and commercialization rights of three drug candidates in Greater China (Mainland, Hong Kong, Macau, Taiwan).

Avapritinib can selectively and strongly inhibit KIT and PDGFRA mutant kinases. The drug is a type I inhibitor designed to target the active kinase conformation; all oncogenic kinases signal through this conformation. Avapritinib has been shown to have a broad inhibitory effect on GIST-related KIT and PDGFRA mutations, including strong activity against activating loop mutations related to resistance to currently approved therapies. Compared with approved multi-kinase inhibitors, avapritinib is significantly more selective for KIT and PDGFRA than other kinases. In addition, avapritinib is uniquely designed to selectively bind to and inhibit the D816 mutation KIT, which is a common disease driver in approximately 95% of patients with systemic mastocytosis (SM). Preclinical studies have shown that avapritinib can strongly inhibit KIT D816V with sub-nanomolar potency and has minimal off-target activity.

In the United States, the European Union, and China, avapritinib was approved in January 2020, September 2020, and April 2021 (trade names: Ayvakit, Ayvakyt, and Taijihua®) for the treatment of PDGFRA exon 18 Adult patients with unresectable or metastatic gastrointestinal stromal tumor (GIST) with mutations (including PDGFRA D842V mutation). It is worth mentioning that Ayvakit is the first precision therapy approved for GIST and the first drug with high activity against GIST with a mutation in exon 18 of the PDGFRA gene.

In March this year, pralsetinib (Phuket Hua®, generic name: pratinib) was approved by the National Food and Drug Administration for use in locally advanced or metastatic transfection-rearrangement (RET) gene fusions that have previously received platinum-containing chemotherapy Treatment of adult patients with non-small cell lung cancer (NSCLC).


(source:internet, reference only)

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