PLEASANTON, Calif.--(BUSINESS WIRE)--Astex Pharmaceuticals, a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics, announces the publication of key clinical data for the novel hypomethylating agent (HMA) guadecitabine (SGI-110) in the prestigious journal, The Lancet Oncology. The publication, entitled “Pharmacokinetic and Pharmacodynamic-guided Phase 1 study of the novel hypomethylating drug guadecitabine (SGI-110) in myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML)”, was released online on August 18, 2015 at http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00038-8/abstract.
The publication describes the first-in-human clinical trial of 93 heavily pre-treated patients (74 AML and 19 MDS) treated with guadecitabine and reports that the drug is well-tolerated, easily administered, and biologically and clinically active in both MDS and AML patients who relapsed after standard of care. Importantly, potent dose-related DNA demethylation is associated with clinical responses in patients treated with guadecitabine, with responders showing significantly more demethylation than non-responders. The study was conducted at 13 leading cancer centers in the US and Canada.
The results described in this publication were used to inform the design of a large Phase 2 study in both treatment naïve and relapsed / refractory AML and MDS, in which over 300 patients were treated with guadecitabine, and a recently-commenced 800-patient global Phase 3 study (ASTRAL-1), in which guadecitabine is being compared with physician’s choice of decitabine, azacitidine, or low-dose cytarabine in treatment naïve AML patients unfit to receive, or unsuitable for, intensive induction chemotherapy.
Lead Author, Jean-Pierre Issa, MD of Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine said, “This study demonstrates that guadecitabine is safe, and showed that the drug resulted in improved PK exposure and PD demethylation over what has been reported for the first-generation HMAs. It also confirmed the importance of DNA demethylation as a PD marker for clinical response." Dr. Issa added, “Guadecitabine’s improved PK and PD profile may improve clinical outcomes in patients with hematologic malignancies, and may also make the drug useful in the treatment of solid tumors, an area in which first generation HMAs are not currently approved.”
Hagop Kantarjian, MD, of The University of Texas MD Anderson Cancer Center, the senior author of the study said: “In this study we observed induced clinical responses in heavily pre-treated patients including prior treatment with current HMAs. Together with the results of a large Phase 2 study to be published later, these data support further investigation, including the recently commenced global Phase 3 study in treatment-naïve AML patients.”
About guadecitabine (SGI-110):
Guadecitabine is a novel next-generation small molecule, DNA hypomethylating agent designed to be administered as a single, small volume, subcutaneous injection. Guadecitabine demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients. Guadecitabine is wholly owned by Astex Pharmaceuticals.
About the SGI-110 study in MDS and AML patients (Study SGI-110-01):
The SGI-110-01 trial is a large (over 400 patients) randomized Phase 1/2 study in patients with MDS or AML. The trial included a Phase I dose escalation stage (93 patients) and a randomized Phase 2 stage (308 patients) that investigated four patient populations: treatment naïve and relapsed / refractory AML and MDS, and also explored both a dailyx5 and a dailyx10 regimen. Additional information about the study can be found online at http://clinicaltrials.gov/ct2/show/NCT01261312.
About the ASTRAL-1 SGI-110 study (Study SGI-110-04)
ASTRAL-1 is a large, global, randomized 800-patient study of guadecitabine (SGI-110) in treatment naïve AML patients who are unfit to receive, or unsuitable for, intensive induction chemotherapy. The trial commenced in March 2015, and compares guadecitabine with physician’s choice of low-dose cytarabine, decitabine or azacitidine. Additional information about the study can be found online at https://www.clinicaltrials.gov/ct2/show/NCT02348489.
About Astex Pharmaceuticals
Astex Pharmaceuticals is dedicated to the discovery and development of novel small molecule therapeutics with a focus on oncology. Astex is developing a proprietary pipeline of novel therapies and has a number of partnered products being developed under collaborations with leading pharmaceutical companies. In October 2013, Astex was acquired by Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan, and operates as a wholly owned subsidiary. The Otsuka Group employs approximately 43,000 people globally, and its products are available in more than 80 countries worldwide.
For more information about Astex Pharmaceuticals, please visit http://www.astx.com
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