Celgene Corporation and Agios Pharmaceuticals, Inc have announced each company has entered into collaboration agreements with Abbott to develop and commercialize companion diagnostic tests on Abbott’s m2000 RealTime System to identify isocitrate dehydrogenase (IDH) mutations in acute myeloid leukemia (AML) patients. Celgene is currently developing enasidenib (AG-221/CC-90007), an IDH2 mutant inhibitor, for the treatment of patients with relapsed or refractory AML who have an IDH2 mutation. Agios is developing AG-120, an IDH1 mutant inhibitor, for the treatment of patients with relapsed or refractory AML who have an IDH1 mutation.
IDH1 and IDH2 mutations occur in approximately 20% of AML patients. An article published online this week in the journal Leukemia (Medeiros, Leukemia 2016) concluded that advances in the understanding of the genetics underlying myeloid malignancies are driving an era of development for targeted treatments such as IDH mutant inhibitors. The authors recommend that IDH mutational analysis should become part of the routine AML diagnostic workup and repeated at relapse to identify patients who may be eligible for targeted investigational treatments currently under clinical study.
“AML is a complex and heterogeneous disease, making it difficult to treat,” said Han Myint, M.D., Vice President, Global Medical Affairs, Myeloid for Celgene. “IDH mutations lead to aberrant DNA methylation, causing a block in myeloid differentiation that leads to disease progression. Molecular profiling is important to identify genomic mutations which may have prognostic and potential treatment implications for patients with AML.”
Abbott’s m2000rt RealTime System, is a polymerase chain reaction (PCR) instrument designed to enable clinical laboratories to automate PCR and results analysis, simplifying the complex and manual steps often associated with molecular diagnostics. Both Celgene and Agios have incorporated this screening into clinical trial designs, including the recently initiated Phase 3 IDHENTIFY trial comparing enasidenib with conventional therapy in older patients with an IDH2 mutation and relapsed or refractory AML (NCT02577406).
“The field of personalized medicine is advancing at a rapid pace for a broad range of medical conditions, especially within hematology-oncology,” said Chris Bowden, M.D., chief medical officer at Agios. “Our collaboration with Abbott will provide a test to help identify AML patients with IDH mutations who are in need of treatment options.” The m2000 system has not been FDA cleared or approved for use with enasidenib or AG-120. Enasidenib and AG-120 have not been approved for any use in any country.