Enasidenib, a targeted inhibitor of mutant IDH2 proteins for treatment of relapsed or refractory acute myeloid leukemia

Stein, Eytan M.

doi:10.2217/fon-2017-0392

Cited by 50 publications

(45 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Enasidenib PK has been well characterized both in healthy subjects and in subjects with relapsed and refractory AML . The absolute bioavailability of Enasidenib after 100 mg oral dose was approximately 57%.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and safety of Enasidenib following single oral doses in Japanese and Caucasian subjects

Li¹,

Liu

Gomez³

et al. 2018

Pharmacology Res & Perspec

View full text Add to dashboard Cite

The aim of this study was to assess and compare the pharmacokinetics (PK) and safety of Enasidenib in healthy adult male Japanese subjects to healthy adult male Caucasian subjects. This was a phase 1, single dose study to evaluate the PK and safety of Enasidenib in healthy adult male Japanese subjects relative to healthy adult male Caucasian subjects. A total of 62 subjects (31 Japanese and 31 Caucasian) were enrolled into three dose cohorts (single doses of 50 mg, 100 mg, or 300 mg Enasidenib). Blood samples for PK assessment were collected up to 672 hours postdose. Safety was evaluated throughout the study. In the present study, we found that PK exposures of Enasidenib and its metabolite AGI‐16903 for Caucasian and Japanese subjects were comparable at the 50, 100, and 300 mg dose levels, demonstrated by that the 90% confidence intervals (CIs) of geometric mean ratios for AUCs and C max between these two populations generally contained 100% from all three treatment cohorts. In conclusion, PK exposures of Enasidenib and its metabolite AGI‐16903 for Caucasians and Japanese subjects were comparable and Enasidenib was safe and well tolerated with no apparent differences between Japanese and Caucasian subjects when administered as single oral doses of 50 mg, 100 mg, and 300 mg.

show abstract

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and safety of Enasidenib following single oral doses in Japanese and Caucasian subjects

Li¹,

Liu

Gomez³

et al. 2018

Pharmacology Res & Perspec

View full text Add to dashboard Cite

show abstract

“…163,164 Enasidenib was approved in August 2017 for the treatment of IDH2mutated, refractory-relapsed AML. Enasidenib, an IDH2 inhibitor, and ivosidenib, an IDH1 inhibitor, were developed as targeted therapies for these subgroups.…”

Section: Acute Myeloid Leukemia (And High-risk Myelodysplastic Syndrome)mentioning

confidence: 99%

Toward the potential cure of leukemias in the next decade

Kantarjian

Keating

Freireich

2018

Cancer

View full text Add to dashboard Cite

Historically, progress in leukemia research has been slow, but it has accelerated recently as a result of understanding the pathophysiology of leukemias and implementing more effective and targeted therapies. This review summarizes the progress across leukemia subsets and projects the potential cure of most leukemias in the next decade. Cancer 2018;124:4301-4313.APL constitutes 5% to 10% of AML cases. It is characterized by the translocation between chromosomes 15 and 17-t(15,17)(q22; q12)-and the corresponding promyelocytic leukemia/retinoic acid receptor α (PML-RARα) molecular abnormality. The discovery of daunorubicin and other anthracyclines in the 1970s was the first step toward

show abstract

“…DNMT3A mutations, particularly R882, increase the resistance to anthracycline; thus, DNMT3A mutation analyses would also be helpful for the selection of therapeutic agents . The presence of IDH1/2 mutations enable the use of IDH inhibitor as a differentiation‐inducing therapy . AML with NPM1 , FLT3‐ITD , and DNMT3A mutations (“triple‐positive”) is significantly related to poor prognosis .…”

Section: Discussionmentioning

confidence: 99%

Investigation of screening method for DNMT3A mutations by high‐resolution melting analysis in acute myeloid leukemia

Mizuta

Yamane

Komai

et al. 2019

Int J Lab Hematology

View full text Add to dashboard Cite

Introduction Acute myeloid leukemia (AML) is a heterogeneous disease associated with various genetic abnormalities. Somatic mutations in nucleophosmin 1 (NPM1), fms‐related tyrosine kinase 3 (FLT3), and DNA methyltransferase 3 alpha (DNMT3A) are the most frequent mutations associated with AML. However, because DNMT3A mutations are broadly distributed, they are challenging to analyze in routine laboratory tests. Hence, we developed a rapid screening method for DNMT3A mutations by high‐resolution melting (HRM) analysis for clinical use at the point of AML diagnosis. Methods The detection limit for DNMT3A mutations from exons 8‐23 by an HRM analysis was investigated using plasmid mixtures. In 69 patients with AML, somatic mutations in NPM1, FLT3‐internal tandem duplication (ITD), FLT3‐tyrosine kinase domain (TKD), DNMT3A, and isocitrate dehydrogenase 1/2 were screened using HRM analysis, and direct sequencing was performed for positive samples. Results High‐resolution melting analysis enabled complete mutation detection in samples with 20% mutant alleles in all regions. In a clinical laboratory test, DNMT3A mutations were detected in 12 cases (17.3%), and we identified five novel mutations. Simultaneous NPM1, FLT3‐ITD, and DNMT3A mutations constituted the most common pattern (30%) in de novo cytogenetically normal AML. Conclusion High‐resolution melting analysis has sufficient performance for the detection of DNMT3A mutations in AML. This approach can facilitate rapid AML genotyping at diagnosis in clinical settings.

show abstract

Enasidenib, a targeted inhibitor of mutant IDH2 proteins for treatment of relapsed or refractory acute myeloid leukemia

Cited by 50 publications

References 47 publications

Pharmacokinetics and safety of Enasidenib following single oral doses in Japanese and Caucasian subjects

Pharmacokinetics and safety of Enasidenib following single oral doses in Japanese and Caucasian subjects

Toward the potential cure of leukemias in the next decade

Investigation of screening method for DNMT3A mutations by high‐resolution melting analysis in acute myeloid leukemia

Contact Info

Product

Resources

About