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TITLE: Advanced Cholangiocarcinoma for ClarIDHy sNDA Submission
Clinical Trial (NCT02989857) Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy) (ClarIDHy)
WHAT IS THE NEXT CATALYST EVENT?
WHEN WILL THE EVENT (OR DID THE EVENT) OCCUR?
05-19-2020 Agios Announces Publication of TIBSOVO® Phase 3 Data in The Lancet Oncology Demonstrating Significant Improvement in Progression-Free Survival Compared to Placebo in Previously Treated IDH1-Mutant Cholangiocarcinoma Patients
MECHANISM OF ACTION
Cancer cells undergo metabolic reprogramming to gain survival advantages as they progress into malignant tumors. Genetic mutations of isocitrate dehydrogenase (IDH), a metabolic enzyme in the tricarboxylic-acid cycle, is one pathway by which some tissues may become cancerous. IDH1 and IDH2 mutant enzymes are found in a number of tumor types, including acute myelogenous leukemia (AML), glioma, chondrosarcoma and cholangiocarcinoma.
Even though the genetic correlation of mutated IDH enzymes to these tumor subtypes was very strong, exactly how mutant IDH could reprogram cellular metabolism to drive cancer formation was a mystery. This lack of understanding of IDH cancer biology represented a major scientific stumbling block in the effort to develop drugs to treat these diseases.
The breakthrough made by Agios scientists was the discovery that mutant IDH1 (and similarly IDH2) acquires a new activity to produce an oncometabolite called 2-hydroxyglutarate (2HG) at exceedingly high levels inside these tumor cells. Subsequent investigative work in collaboration with several renowned academic researchers revealed that elevated 2HG causes changes in gene function that are independent of intrinsic DNA sequence (epigenetic regulation). This causes a block in the normal process of cellular differentiation from a precursor cell into different mature cell types, and instead leads to cancerous transformation
Updated by MV
IDH1, Advanced Cholangiocarcinoma, ClarIDHy, Agios, AGIO
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