The first gist precision therapy ayvakit Phase 3 clinical failure

Blueprint Pharmaceuticals (Blueprint Pharmaceuticals) announced that Ayvakit (avapritinib) failed to reach the primary endpoint of progression-free survival (PFS) in phase 3 clinical trial VOYAGER for patients with local late-stage non-removal or metastasis gastrointestinal mesothelioma (GIST).VOYAGER (NCT03465722) is a global, open-label, randomized Phase 3 clinical trial designed to evaluate the efficacy and safety of Ayvakit in patients with regorafenib (Rigfini) in third- or fourth-line GIST. The main therapeutic endpoint is to evaluate the patient's PFS through a single-blind, independent center radiology examination based on GIST's improved solid tumor response assessment standard 1.1 (mRECIST 1.1).Top-line data showed that the average PFS was 4.2 months for patients in the Ayvakit treatment group, 5.6 months for the Rigfini group, and the difference between the median PFSs in the two groups was not statistically significant. But the Ayvakit group showed a slightly higher response rate than Rigfini (17 percent to 7 percent).Ayvakit generally has good tolerance and most adverse events are reported as Level 1 or 2. The security results are consistent with previously reported data and no new security signals are observed.GIST is a gastrointestinal sarcoma that originates in gastrointestinal wall cells and is most commonly found in the stomach or small intestine. Most patients are diagnosed between the ages of 50 and 80, usually by accident during gastrointestinal bleeding, surgery or imaging, and in rare cases caused by a ruptured tumor or gastrointestinal obstruction. The disease is a rare cancer with an annual incidence rate of 3-7 people per million in the United States. About 6% of newly diagnosed patients carry PDGFA exon 18 mutations. The most common mutation is the D842V mutation, which causes patients to develop resistance to all other approved therapies.Currently, clinically Imatini is a first-line therapy for metastasis relapse/non-resection giST, with Sunitinib (Shonitinib) or Rigfini as second-line therapy after drug resistance. However, treatment options are very limited for patients with KIT-driven GIST who develop disease progression or develop resistance, and approved therapies offer PFS for up to 6 months with a remission rate of only 5% to 7%. For patients with PDGFR alpha D842V-driven GIST, there is currently no effective treatment option, and disease progression usually occurs in as little as three months.Ayvakit is a powerful, highly selective KIT and PDGFR alpha mutation kinase inhibitor that has been shown to have a wide range of inhibitory effects in THET patients with KIT and PDGFR alpha mutations, including the PDGFR alpha gene D842V mutation and other primary or secondary drug-resistant mutations. In 2017, a Phase 1 clinical study showed that the drug had a 100% disease control rate, a 100% tumor reduction rate, and a 12-month PFS rate of 78% in patients with PDGFR alpha exon 18 D842V mutant GIST.In January, Ayvakit received FDA approval to treat adult patients with non-removable or metastasis GIST with PDGFR alpha exon 18 mutations, including PDGFR alpha D842V mutations. Ayvakit is also the first precision therapy approved for the treatment of genomically explicit GIST patients and the only highly effective treatment for patients with PDGFR alpha exon 18 mutant GIST. In June 2018, Blueprint Pharmaceuticals announced an exclusive partnership and licensing agreement with Keystone Pharmaceuticals to develop and commercialize Ayvakit and other drug candidates in Chinese mainland and Hong Kong, Macau and Taiwan.Based on VOYAGER trial data, Blueprint Pharmaceuticals plans to stop further development of Ayvakit in non-PDGFRA exon 18 mutation GIST patients, but will continue to commercialize Ayvakit for the treatment of approved patient groups in the United States and seek approval from other countries to treat that patient group. Meanwhile, Blueprint Pharmaceuticals expects the European Commission to approve the drug's listing application in the third quarter of this year.At the same time, Blueprint Pharmaceuticals is developing Ayvakit worldwide for hypertrophic cell hypertrophicity (SM). The FDA has awarded Ayvakit breakthrough therapy for the treatment of advanced SM, including invasive SM subtypes, as well as SM patients with associated blood tumors and hypertrophy cell leukemia. (Sina Pharmaceutical News)