t-free survival (EFS; event defined as no complete remission within 60 days of the start of induction therapy, relapse or death) was significantly higher for Rydapt plus chemotherapy versus chemotherapy alone(median of 8.2 months compared to 3.0 months, HR = 0.78, 95% CI 0.66, 0.93 and 2 sided p=0.004). RATIFY is the largest worldwide clinical trial in newly diagnosed FLT3-mutated AML to date, as 3,279 AML patients were screened for the FLT3 mutation and 717 patients were enrolled. All FLT3+patients enrolled in the trial were treated regardless of whether or not cytogenetic status was normal or abnormal.
The most frequent adverse reactions (incidence greater than or equal to 20%) in the Rydapt plus chemotherapy arm were febrile neutropenia, nausea, vomiting, mucositis, headache, musculoskeletal pain, petechiae (small red skin spots), device-related infection, epistaxis, hyperglycemia and upper respiratory tract infections. The most frequent Grade 3/4 adverse reactions (incidence greater than or equal to 10%) were febrile neutropenia, device-related infection and mucositis.
In order to identify FLT3+ AML patients who may benefit from Rydapt, Novartis collaborated with Invivoscribe Technologies, Inc. on the development of LeukoStrat® CDx FLT3 Mutation Assay, a companion molecular diagnostic test, which was also approved by the FDA today. LeukoStrat® CDx FLT3 Mutation Assay is the first molecular companion diagnostic in AML and identifies both FLT3 internal tandem duplication(ITD)and tyrosine kinase domain(TKD)mutations and is performed by The Laboratory for Personalized Molecular Medicine, a subsidiary of Invivoscribe Technologies, Inc.
Rydapt provides an innovative treatment option for advanced SM
Advanced SM is a rare blood disorder characterized by uncontrolled growth and accumulation of mast cells-or mediators of allergic responses - in one or more organs. In advanced SM, mast cells accumulate in such high quantities that they begin to cause organ damage. Median overall survival is currently less than six months for mast cell leukemia, two years for SM-AHN and 3.5 years for ASM.
Rydapt is approved in the US for the treatment of adult patients with ASM, SM-AHN, or mast cell leukemia. The approval of Rydapt was based on two single-arm open-label multicenter trials, including the Phase II study (CPKC412D2201), which was the largest and longest-running prospective trial ever conducted in this ultra-rare disorder.
The efficacy of Rydapt was established on the basis of confirmed complete remission (CR) plus incomplete remission (ICR) by six cycles of treatment per the modified Valent criteria(n=89), in which CR and ICR are the two most rigorous subcategories of a major response. This analysis demonstrated an overall response rate of 21% (95% CI). Efficacy was also assessed in a post-hoc analysis using the 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis (IWG-MRT-ECNM) consensus criteria (n=115). This assessment estimated complete remission or partial remission rate of 17% (95% CI)。
The most frequent adverse reactions (incidence greater than or equal to 20%), excluding laboratory terms, were nausea, vomiting, diarrhea, edema, musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, constipation, pyrexia, headache and dyspnea. The most frequent Grade 3 or greater adverse reactions (incidence greater than or equal to 5%), ex |
