The National Drug Administration (NMPA) Accepts Applications For Two Indications For The First-in-class Gastrointestinal Stromal Tumor Precise Targeted Drug Avapritinib

- Apr 26, 2020-

On April 23, 2020, Keystone Pharmaceutical (Suzhou) Co., Ltd. (hereinafter referred to as "Keystone Pharmaceutical", Hong Kong Stock Exchange code: 2616) announced that the National Drug Administration (NMPA) has accepted gastrointestinal stromal tumors (GIST) New drug marketing application for the precision-targeted drug avapritinib, covering two indications, for the inoperable resection of exon 18 mutations (including PDGFRA D842V mutation) carrying platelet-derived growth factor receptor alpha (PDGFRA) Or adult patients with metastatic GIST, and adult patients with four-line non-surgical or metastatic GIST. Avapritinib is a potent, highly selective oral inhibitor against KIT and PDGFRA gene mutations under development, developed by company partner Blueprint Medicines. This is also the first new drug listing application accepted by NMPA by CStone Pharmaceuticals, marking an important step in the company's commercial transformation.

About 1-1.5 / 100,000 (14,000-21,000) of newly diagnosed GIST patients in China every year [Zhou Yanbing. Current status of diagnosis and treatment of gastrointestinal stromal tumors [J]. Chinese Journal of General Surgery, 2017, 032 (007) : 549-552.], About 90% of GIST patients are associated with KIT or PDGFRA gene mutations. In January of this year, the FDA approved its use for the treatment of adult patients with PDGFRA exon 18 mutations that are not surgically resectable or metastatic GIST, becoming the first and only marketed in the United States for the precise treatment of PDGFRA exon 18 mutations. Targeting drugs.

Dr. Jiang Ningjun, Chairman and CEO of CStone Pharmaceuticals, said: "Only three months after avapritinib was approved by the US FDA, CStone Pharmaceuticals has submitted avapritinib's new drug marketing applications in Taiwan and Mainland China, and hopes to be able to do so soon Bring this kind of first-in-class precision targeted drugs to advanced GIST patients in Greater China. As the company's pace of commercial transformation continues to accelerate, in the next few months, CStone Pharmaceuticals will also deliver many important products in China New drug application for multiple indications. "

Professor Shen Lin, deputy dean of Peking University Cancer Hospital, director of the Department of Gastroenterology, and principal investigator of avapritinib in China, said: "Avapritinib is in advanced GIST with PDGFRA exon 18 mutation and in GIST patients with fourth-line treatment. Demonstrates very good antitumor activity, and is safe and well tolerated. Due to the very limited benefit of patients with existing therapies, these two types of GIST patients have highly unmet treatment needs. As a clinician, we expect Hope that avapritinib will be approved as soon as possible and become a new treatment option for patients with advanced GIST. "

In November 2019, the CTOS annual meeting announced the results of the NAVIGATOR Phase I clinical trial on avapritinib in PDGFRA exon 18 mutations and patients receiving fourth-line GIST. The data as of November 16, 2018 shows:

1. The 43 patients with PDGFRA exon 18 mutation and 111 patients with fourth-line treatment received an initial dose of avapritinib 300 mg or 400 mg once daily, and the efficacy can be evaluated.

2. Among patients with PDGFRA exon 18 mutation, ORR was 86% (1 patient to be confirmed), median duration of remission (DOR) was not reached

3. Among the fourth-line GIST patients, ORR reached 22% (1 patient to be confirmed), with a median DOR of 10.2 months.

It is gratifying that the preliminary data of the China Phase I / II bridging study carried out by CStone Pharmaceuticals shows that the safety and pharmacokinetic characteristics of patients with advanced GIST in China are consistent with the NAVIGATOR global study data and are well tolerated .

Dr. Yang Jianxin, Chief Medical Officer of CStone Pharmaceuticals, said: "At present, the treatment of advanced GIST in China is mainly the sequential use of tyrosine kinase inhibitors (TKIs). The effect is very small. On the other hand, Chinese fourth-line GIST patients are facing multiple difficulties such as multiple drug resistance mutations and lack of effective approved therapies. I am very happy to see that the current bridging study data of avapritinib in China is consistent with the results of the NAVIGATOR global study And look forward to its early benefit to more advanced GIST patients who are in need of innovative therapies. "

CStone Pharmaceuticals has reached an exclusive cooperation and authorization with Blueprint Medicines, and obtained the exclusive development and commercialization authorization of many drugs including avapritinib in Greater China. Blueprint Medicines reserves the right to develop and commercialize related drugs in other parts of the world.

About Avapritinib

Avapritinib is a KIT and PDGFRA mutant kinase inhibitor that is under investigation, potent and highly selective. It is a type 1 kinase conformational inhibitor used in the treatment of GIST and can directly bind to the active kinase conformation of KIT and PDGFRA mutations leading to downstream signaling activation. Avapritinib has confirmed the inhibitory effect of KIT and PDGFRA mutations in GIST. At present, the main drug resistance mechanism of the approved treatment in Greater China is caused by the activation loop mutation. Avapritinib suppresses mutations at this site, resulting in strong clinical activity.

Blueprint Medicines is advancing the development of wider clinical programs for avapritinib, including GIST for multi-line therapy, and advanced, inert and smoking systemic mastocytosis (SM).

Avapritinib is a kinase inhibitor approved by the US FDA under the product name AYVAKITTM for the treatment of adult patients with non-surgically excised or metastatic GIST carrying PDGFRA exon 18 mutation (including PDGFRA D842V mutation).

Avapritinib has not been approved by the US FDA for the treatment of any other indications, and has not been approved by the TFDA, NMPA or other regional health regulatory authorities for any indications.