Decitabine/Cedazuridine: First Approval
- PDF / 839,078 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 85 Downloads / 130 Views
ADISINSIGHT REPORT
Decitabine/Cedazuridine: First Approval Sohita Dhillon1
© Springer Nature Switzerland AG 2020
Abstract A fixed dose oral combination (FDC) of decitabine and cedazuridine (Inqovi®), is being developed by Astex Pharmaceuticals (a subsidiary of Otsuka Pharmaceuticals) for the treatment of various cancers like myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemia (AML), glioma and solid tumours. Decitabine, a DNA methyltransferase inhibitor approved for the treatment of MDS and CMML, is degraded by cytidine deaminase in the gastrointestinal tract and liver, thereby limiting oral bioavailability. Cedazuridine is a proprietary, patented cytidine deaminase inhibitor that, when added to decitabine, increases oral bioavailability of the drug. In July 2020, decitabine/cedazuridine received its first approval in the USA and Canada for the treatment of MDS and CMML. In the USA, it is indicated for use in adults with MDS and CMML, including previously treated and untreated, de novo and secondary MDS with the following French–American–British subtypes (refractory anaemia, refractory anaemia with ringed sideroblasts, refractory anaemia with excess blasts and CMML) and intermediate-1, intermediate-2 and high-risk International Prognostic Scoring System groups. Clinical studies for AML, glioma and solid tumours are underway in several countries worldwide. This article summarizes the milestones in the development of decitabine/cedazuridine leading to this first approval for the treatment of MDS and CMML.
Decitabine/Cedazuridine (Inqovi®): Key points
1 Introduction
An oral FDC of decitabine and cedazuridine is being developed by Astex Pharmaceuticals for the treatment of cancers, such as MDS, CMML and AML
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of the bone marrow haematopoietic stem cells, characterized by impaired haematopoiesis, peripheral blood cytopenias, increased blast populations in the peripheral blood and/or bone marrow and a higher risk of developing acute myeloid leukaemia (AML) [1, 2]. While allogeneic hematopoietic stem cell transplant is the only potentially curative option for MDS (and other advanced haematological malignancies), many patients are not eligible for the procedure and the hypomethylating agents (HMAs) azacitidine and decitabine are the mainstay of therapy to alleviate cytopenia, control disease and prolong survival in these patients [1, 3–5]. HMAs are cytidine-nucleoside analogues that incorporate into DNA during the S-phase of the cell cycle and covalently bind DNA methyltransferase 1, which is then degraded and depleted within the cell, resulting in reduced methylation of CpG residues in genomic DNA, altered epigenetic pattern and modified gene expression [3, 6]. HMAs are administered parenterally for 5–7 days per 28-day treatment cycle, with multiple treatment cycles necessary to achieve a response [7]. Interruption of therapy in patients that respond to treatment can result in disease
Receiv
Data Loading...
