Astex Pharmaceuticals Announces Orphan Drug Designation for Guadecitabine (SGI-110) in the Treatment of Acute Myeloid Leukemia

Astex Pharmaceuticals Announces Orphan Drug Designation for Guadecitabine (SGI-110) in the Treatment of Acute Myeloid Leukemia

  •  FDA has granted an orphan drug designation for Astex Pharmaceuticals’ investigational drug, guadecitabine (SGI-110), in the treatment of acute myeloid leukemia (AML). 
  • Over 20,000 new cases of AML are diagnosed annually in the US, and the prognosis for patients who are unfit to receive standard intensive induction chemotherapy is poor. Currently, there is no drug specifically approved for these patients in the US.
  • Guadecitabine is a novel, next-generation hypomethylating agent (HMA) which reverses aberrant DNA methylation, one of the key mechanisms associated with AML and other malignancies, by inhibiting DNA methyltransferase enzymes.
  • Guadecitabine is currently being evaluated in a large global Phase 3 study (ASTRAL- 1) in treatment naïve AML patients who are unfit to receive, or unsuitable for, intensive induction chemotherapy.

Pleasanton, CA, USA, October 6th, 2015. Astex Pharmaceuticals, a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics, announced today that its novel hypomethylating agent, guadecitabine (SGI-110), has been granted an orphan drug designation by the US FDA.

Guadecitabine has been evaluated in multiple Phase 1 and Phase 2 trials to investigate its potential in the treatment of a range of cancers. The company has recently completed a large (over 400 patients) randomized Phase 1/2 study in patients with myelodysplastic syndromes (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 different patient populations: treatment naïve and relapsed/refractory AML and MDS. The trial demonstrated that guadecitabine was clinically active and well tolerated in all four patient groups. The results from the Phase 1 portion of the trial were recently published in Lancet Oncology (http://www.thelancet.com/journals/lanonc/article/PIIS1470- 2045%2815%2900038-8/abstract). Additional information about the study can be found online at http://clinicaltrials.gov/ct2/show/NCT01261312.

Guadecitabine is now being evaluated in the ASTRAL-1 trial, a large, global, randomized 800- patient study in treatment naïve AML patients who are unfit to receive, or unsuitable for, intensive induction chemotherapy. The trial 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.

Mohammad Azab, Astex’s President and Chief Medical Officer said: “We are delighted that FDA has granted orphan drug status to guadecitabine for the treatment of AML. This designation supports our conviction that new therapies are desperately needed for patients who are diagnosed with AML, particularly those for whom standard intensive induction chemotherapy is unsuitable, and helps underpin the rationale for commencing the ASTRAL-1 trial, the largest clinical study ever conducted in this group of patients.”

About Orphan Drug Designation

Orphan Drug designation is granted to drugs or biologics that treat a rare disease or condition affecting fewer than 200,000 people in the US. Orphan Drug designation by the FDA qualifies the sponsor for incentives provided for in the Orphan Drug Act, which can include protocol assistance for clinical trials, prescription drug user fee waivers, tax incentives and seven years of market exclusivity.

About Acute Myeloid Leukemia (AML)

AML is the most common hematological malignancy in adults. Over 20,000 new cases of AML are diagnosed annually in the US. Although 60%-75% of AML patients <60 years of age will achieve complete response (CR) with standard intensive induction chemotherapy, approximately 30%-40% of patients will die from their disease. The outlook for patients >60 years old is significantly worse with response rates < 50%, cure rates remaining at <10% and a median survival of <1 year. These figures have not significantly improved within the last 3 decades. These patients have few therapeutic options. Effective, less toxic therapies are needed for the treatment of AML, particularly for elderly patients whose comorbidities make them unfit for intensive therapy.

About guadecitabine (SGI-110):

Guadecitabine is a novel next-generation, small molecule DNA hypomethylating agent formulated as a single, small volume, subcutaneous injection. The product was designed to deliver longer exposure to the active moiety, decitabine, compared to iv decitabine and more efficient delivery into key tissues, including the bone marrow. 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 Astex Pharmaceuticals Astex is a leader in innovative drug discovery and development, committed to the fight against cancer and diseases of the central nervous system. 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 became a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan. 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.

For more information about Otsuka Pharmaceutical, please visit http://www.otsuka.com/en/

CONTACT:

Martin Buckland
Chief Corporate Officer
Astex Pharmaceuticals, Inc.
4420 Rosewood Drive, Suite 200
Pleasanton, CA 94588 Tel: +1 (925) 560-0100
Email: email_mb

Astex Pharmaceuticals Announces Publication of Key Clinical Data for Guadecitabine (SGI-110) in The Lancet Oncology

Astex Pharmaceuticals Announces Publication of Key Clinical Data for Guadecitabine (SGI-110) in The Lancet Oncology

  • Guadecitabine (SGI-110) is a novel, next-generation hypomethylating agent (HMA) which reverses aberrant DNA methylation by inhibiting DNA methyltransferase enzymes.
  • This publication describes a first-in-human pharmacokinetic and pharmacodynamic guided dose-escalation study of guadecitabine (SGI-110) in adults with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), refractory to, or relapsed after, standard treatment.

Pleasanton, CA, USA, August 18, 2015. 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 welltolerated, 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 does 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

For more information about Otsuka Pharmaceutical, please visit http://www.otsuka.com/en/

CONTACT:
Martin Buckland
Chief Corporate Officer
Astex Pharmaceuticals, Inc.
4420 Rosewood Drive, Suite 200
Pleasanton, CA 94588
Tel: +1 (925) 560-0100
Email: email_mb