Blueprint Medicines today announced that its highly selective RET inhibitor pralsetinib (BLU-667) has achieved positive top-line results in ARROW, a Phase 1/2 clinical study of RET fusion-positive non-small cell lung cancer (NSCLC) patients . Blueprint Medicines has begun submitting a rolling NDA for this indication to the US FDA and is expected to complete its submission in the first quarter of this year. In addition, Blueprint Medicines plans to submit another new drug application for pralsetinib in the second quarter of this year to treat patients with myeloid thyroid tumor (MTC) previously treated with too many kinase inhibitors.
Public data shows that lung cancer is the malignant tumor with the highest morbidity and mortality in the world, of which about 80% -85% are NSCLC, and the incidence of RET fusion in non-small cell lung cancer is about 1% ~ 2%. In MTC, almost all hereditary and about 50% of patients with sporadic medullary thyroid cancer are associated with mutations in the RET gene. MTC is a type of thyroid cancer. It is a common endocrine malignant tumor. Its incidence has increased significantly in recent years, and there is currently no effective standard treatment plan approved in China.
In response to this clinical need, the Blueprint Medicines research team designed and developed an oral, potent, highly selective RET inhibitor pralsetinib that targets mutations in the RET gene based on its proprietary compound library. Public information shows that pralsetinib has consistently shown sub-nanomolar levels of efficacy against the most common RET gene fusions, activation mutations, and drug-resistant mutations in preclinical studies. And the drug's selectivity for RET is significantly improved compared to approved multikinase inhibitors. Among them, the activity on RET was increased by more than 80 times compared with VEGFR2. Cornerstone Pharmaceuticals obtained exclusive development and commercialization licenses for pralsetinib in mainland China, Hong Kong, Macau and Taiwan in June 2018.
Currently, pralsetinib has obtained a number of regulatory qualifications. In April 2018, it was granted orphan drug status by the FDA to treat NSCLC patients with RET rearrangement. In February last year, the FDA granted a breakthrough therapy designation for patients with RET mutant MTC who require systemic treatment and no alternative treatment options. Last May, the FDA was granted another breakthrough therapy designation for patients with RET fusion-positive NSCLC who failed platinum-based chemotherapy.
Data from the Phase 1/2 ARROW trial as of November 18, 2019 showed that among 80 subgroups of RET fusion-positive NSCLC patients who had previously received platinum chemotherapy, pralsetinib treatment resulted in an objective response rate (ORR) of 61 %, And reduced tumors in 95% of patients, including 14% of patients with complete regression of the target tumor. In a subgroup of 26 newly treated patients, pralsetinib treatment resulted in an ORR of 73% of patients, of which 12% achieved complete response (CR), and tumors shrank in all patients. Details of the trial will be announced at a future medical conference.
"As the clinical data of pralsetinib matures, we also have data on the antitumor activity of pralsetinib in patients with brain metastases. We believe that pralsetinib has the potential to treat patients with RET fusion-positive NSCLC, including newly diagnosed metastatic patients and unresectable "Advanced patients," said Andy Boral, MD, Chief Medical Officer, Blueprint Medicines. "Now that we have obtained positive top-line data, we look forward to working with the US FDA to bring pralsetinib to patients in need as soon as possible.
今日，Blueprint Medicines公司宣布，其高选择性RET抑制剂pralsetinib（BLU-667），在治疗RET融合阳性非小细胞肺癌（NSCLC）患者的1/2期临床研究ARROW中，获得积极的顶线结果。Blueprint Medicines已开始向美国FDA递交这一适应症的滚动新药申请（rolling NDA），预计将在今年第一季度完成递交。此外，Blueprint Medicines还计划在今年第二季度递交pralsetinib的另一个新药申请，治疗先前接受过多激酶抑制剂治疗的甲状腺髓样瘤（MTC）患者。
“随着pralsetinib的临床数据日趋成熟，我们也得到了pralsetinib对脑转移瘤患者的抗肿瘤活性数据。我们认为，pralsetinib有潜力治疗RET融合阳性NSCLC患者，包括新诊断的转移性患者和不可切除的晚期患者，”Blueprint Medicines首席医学官Andy Boral医学博士说：“现在，我们已获得了积极的顶线数据，我们期待与美国FDA的下一步合作，尽快把pralsetinib带给有需要的患者。“