• Real-world evidence on use of oral decitabine and cedazuridine in the treatment of myelodysplastic syndromes to be featured in an oral presentation; results of several additional studies in hematological malignancies were accepted for poster presentations

Princeton, N.J., and Pleasanton, Calif., November 17, 2023 – Taiho Oncology Inc. and Astex Pharmaceuticals, Inc. announced today details of studies to be presented at the 65^th American Society of Hematology (ASH) Annual Meeting, to be held Dec. 9-12, 2023, in San Diego. Among these data are the results of a real-world study of oral decitabine and cedazuridine in patients with myelodysplastic syndromes (MDS), which will be featured in an oral presentation.

“Real-world data in healthcare is invaluable as it provides us with a closer look at actual patient experiences outside the clinical trial setting,” said Tehseen Salimi, MD, MHA, Senior Vice President Medical Affairs, Taiho Oncology. “This study is the first to explore how an oral therapy may help patients with MDS adhere to their treatment regimen, while reducing both personal and disease burden. Oral decitabine and cedazuridine is a potentially important treatment option for people living with this form of cancer.”

Below are viewing details of this oral presentation.

The above study was sponsored by Taiho Oncology.

In addition, investigational compounds from Astex Pharmaceuticals that are currently in various stages of clinical development will be featured in several poster presentations.

 The above studies are being sponsored by Astex Pharmaceuticals, Inc.

About Taiho Oncology, Inc.

The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development and commercialization of orally administered anti-cancer agents for various tumor types. Taiho Oncology has a robust pipeline of small molecule clinical candidates targeting solid tumor and hematological malignancies, with additional candidates in pre-clinical development. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company’s European and Canadian operations, which are located in Zug, Switzerland and Oakville, Ontario, Canada.

For more information, visit https://www.taihooncology.com/, and follow us on LinkedIn and Twitter.

About Astex Pharmaceuticals, Inc.

Astex Pharmaceuticals, Inc. is committed to the fight against cancer. Astex is developing a proprietary pipeline of novel therapies for the treatment of solid tumors and hematological malignancies. Astex is a member of the Otsuka group of companies. The group also includes Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Taiho Oncology, Inc.

Astex, the Astex logo, Taiho Oncology, and the Taiho Oncology logo are registered trademarks of Otsuka Holdings Co., Ltd. or its subsidiaries.

###

Taiho Oncology Contact:
Judy Kay Moore
(574) 526-2369
jumoore@taihooncology.com

Astex Pharmaceuticals:
Martin Buckland
Astex Pharmaceuticals, Inc.
(+1) 925-560-0100
martin.buckland@astx.com

¹Investigational Oral DNA Methyltransferase Inhibitor

² X-Linked Inhibitor of Apoptosis Protein (XIAP)/Cellular Inhibitor of Apoptosis Protein (cIAP) Antagonist – Astex Pharmaceuticals, Inc. investigational agent being developed in collaboration with Taiho Oncology, Inc.

Patients in Phase 3 ASCERTAIN study with biallelic TP53 mutations achieved median overall survival (mOS) of 13 months; mOS in the overall study population was 32 months

 Results indicate potential utility of this oral hypomethylating agent in patients with MDS harboring a TP53 mutation, which is an independent prognostic factor for poor outcomes

PRINCETON, N.J. and PLEASANTON, CA, December 12, 2022 – Taiho Oncology, Inc. and Astex Pharmaceuticals, Inc. today announced preliminary data from the Phase 3 ASCERTAIN trial assessing overall and leukemia-free survival in adults with intermediate and high-risk myelodysplastic syndromes (MDS) including chronic myelomonocytic leukemia (CMML) harboring biallelic TP53 mutations following treatment with oral decitabine and cedazuridine (ASTX727). The data are being presented today as an oral presentation (Abstract #854) at the 64^th American Society of Hematology (ASH) Annual Meeting in New Orleans.

This analysis evaluated the impact mutation profile of patients from the ASCERTAIN trial on overall survival (OS) and leukemia-free survival (LFS); this was based on the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines (NCCN Guidelines®) in Oncology for Myelodysplastic Syndromes (Version 1.2023-September 12, 2022) with a focus on the TP53 mutant population. In the study, the population of patients harboring a TP53 mutation (44 of 125 patients) was characterized by allelic status: 14 patients had biallelic mutations and 30 patients had monoallelic mutations without other chromosomal deletions. The median OS (mOS) in patients treated with ASTX727 with biallelic vs. monoallelic mutations was 13.0 months (95% Confidence Interval [CI]: 5.3, 29.1) vs. 29.2 months (95% CI: 19.8, NE).

“The overall results of this post-hoc analysis from ASCERTAIN studying the patients with mutated TP53 are of interest given the typically poor outcomes in these patients,” said Michael Savona, MD, Director of Hematologic Malignancies Research and Early Therapy Program, and Professor of Internal Medicine and Cancer Biology at Vanderbilt University, and co-principal investigator on the study. “This analysis supports the emerging hypothesis that higher burden of mutant TP53 cells connotes poorer risk, and the fixed-dose combination of oral decitabine and cedazuridine may serve as a reasonable option in these patients.”

More broadly, mOS and median LFS (mLFS) in patients with MDS and CMML harboring a TP53 mutation treated with ASTX727 were 25.5 and 22.1 months, respectively, compared to 33.7 and 31.7 months, respectively, in patients with wild-type TP53 status. The mOS and mLFS in the overall ASCERTAIN population were 32 and 29 months, respectively. Of note, the percentage of patients in the trial harboring a TP53 mutation (35%) was substantially higher than the standard patient population, which is approximately 8-12%.[1]

“There remains a significant unmet need for patients with MDS and CMML, particularly for those with mutations that typically don’t respond well to treatment, which is why we are encouraged by what we see in the ASCERTAIN trial,” said Tim Whitten, President and CEO of Taiho Oncology, Inc. “The results build on the body of evidence supporting the utility of oral decitabine and cedazuridine, and we look forward to additional research to assess this combination as a treatment option for these patients.”

Additional Data Presentations on ASTX727
In a second oral presentation, results of a Phase 1 study (Abstract #461) that explored the optimal dosing schedule of low-dose ASTX727 in patients with lower-risk MDS, were presented. The study found that a dosing schedule of 10 mg decitabine/100 mg cedazuridine daily for five days led to balanced clinical efficacy with an acceptable and manageable safety profile. Based on the results of the study, this dosing schedule was chosen as the recommended dose for an ongoing Phase 2 study that is comparing this regimen to 35 mg decitabine/100 mg cedazuridine for three days in a 28-day cycle. The data were presented by Guillermo Garcia-Manero, MD, on Sunday, December 11 during the “Myelodysplastic Syndromes – Clinical and Epidemiological II” oral session.

In addition, data from the first real-world study on treatment patterns and characteristics for MDS patients initiating ASTX727 (Abstract #1760) were presented by Amer Zeidan, MD, on Saturday, December 10 during the “Myelodysplastic Syndromes – Clinical and Epidemiological: Poster I” session. Parenteral administration of hypomethylating agents has been associated with additional patient burden. Based on the results of this study, characteristics were similar among patients initiating ASTX727 and parenteral hypomethylating agents. Trends in treatment patterns suggest comparable or improved compliance with oral decitabine and cedazuridine treatment regimen at home compared with parenteral treatment in the clinical setting.

About ASCERTAIN
The Phase 3 ASCERTAIN clinical trial was a multicenter, randomized, open-label, crossover pharmacokinetics (PK) study comparing oral decitabine (35mg) and cedazuridine (100mg) fixed-dose combination tablet given once daily for 5 days on a 28-day cycle to IV decitabine (20mg/m²) administered as a daily 1-hour IV infusion for 5 days on a 28-day cycle, in the first 2 cycles in patients with MDS and CMML. Patients continued to receive oral decitabine and cedazuridine from Cycle 3 onwards. The primary endpoint of the study was total 5-day area-under-the-curve (AUC) equivalence of oral decitabine and cedazuridine and IV decitabine.

For more information about ASCERTAIN, please visit: https://www.clinicaltrials.gov/ct2/show/NCT03306264?term=cedazuridine&draw=3&rank=19.

 
INDICATIONS
Decitabine and cedazuridine, marketed under the brand name INQOVI®, is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.^[2] 

INQOVI is the first and only oral hypomethylating agent approved by the FDA and by Health Canada for the treatment of adults with intermediate and high-risk MDS including CMML.²

Commercialization of INQOVI in the U.S. and Canada is conducted by Taiho Oncology, Inc. and Taiho Pharma Canada, Inc., respectively. Astex and Taiho are members of the Otsuka group of companies.

IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS

Myelosuppression
Fatal and serious myelosuppression can occur with INQOVI. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%. Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrile neutropenia) is the most frequent cause of INQOVI dose reduction or interruption, occurring in 36% of patients. Permanent discontinuation due to myelosuppression (febrile neutropenia) occurred in 1% of patients. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.

Fatal and serious infectious complications can occur with INQOVI. Pneumonia occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsis occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1%.

Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors and anti‑infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.

Embryo-Fetal Toxicity
INQOVI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise patients to use effective contraception during treatment and for 6 months (females) or 3 months (males) after last dose.
 
ADVERSE REACTIONS
Serious adverse reactions in > 5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse reactions included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and one case each of cerebral hemorrhage and sudden death.

The most common adverse reactions (≥ 20%) were fatigue (55%), constipation (44%), hemorrhage (43%), myalgia (42%), mucositis (41%), arthralgia (40%), nausea (40%), dyspnea (38%), diarrhea (37%), rash (33%), dizziness (33%), febrile neutropenia (33%), edema (30%), headache (30%), cough (28%), decreased appetite (24%), upper respiratory tract infection (23%), pneumonia (21%), and transaminase increased (21%). The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased (81%), platelet count decreased (76%), neutrophil count decreased (71%), and hemoglobin decreased (55%).

USE IN SPECIFIC POPULATIONS

Lactation
Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with INQOVI and for 2 weeks after the last dose.

Renal Impairment
No dosage modification of INQOVI is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] of 30 to 89 mL/min based on Cockcroft-Gault). Due to the potential for increased adverse reactions, monitor patients with moderate renal impairment (CLcr 30 to 59 mL/min) frequently for adverse reactions. INQOVI has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min) or end-stage renal disease (ESRD: CLcr <15 mL/min).
 
Please see the accompanying Full Prescribing Information.
 
About Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)
Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. U.S. incidence of MDS is estimated to be 10,000 cases per year, although the condition is thought to be under-diagnosed.[3]^,[4] The prevalence has been estimated to be from 60,000 to 170,000 in the U.S.[5] MDS may evolve into acute myeloid leukemia (AML) in one-third of patients.[6] The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML.

CMML is a clonal hematopoietic malignancy characterized by accumulation of abnormal monocytes in the bone marrow and in blood. The incidence of CMML in the U.S. is approximately 1,100 new cases per year,[7] and CMML may transform into AML in 15% to 30% of patients.[8]
 
About Decitabine and Cedazuridine Fixed-Dose Combination (ASTX727)
ASTX727 is an orally administered, fixed dose combination of the approved anti-cancer DNA hypomethylating agent, decitabine, together with cedazuridine,³ an inhibitor of cytidine deaminase.⁴ By inhibiting cytidine deaminase in the gut and the liver, the fixed dose combination is designed to allow for oral delivery of decitabine over five days in a given cycle to achieve comparable systemic exposure to IV decitabine administered over five days.

The oral decitabine and cedazuridine fixed-dose combination has been evaluated in a Phase 1/2 pharmacokinetics-guided dose escalation and dose confirmation study, and a Phase 3 exposure equivalence study in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) – the ASCERTAIN study.
 
About Taiho Oncology, Inc.
The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development of orally administered anti-cancer agents and markets these medicines for a range of tumor types in the U.S. Taiho Oncology’s growing pipeline of antimetabolic and selectively targeted anti-cancer agents is led by a world-class clinical development organization. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company’s European and Canadian operations, which are located in Zug, Switzerland and Oakville, Ontario, Canada.

For more information, visit www.taihooncology.com.
 
About Astex
Astex Pharmaceuticals, Inc. is committed to the fight against cancer. Astex is developing a proprietary pipeline of novel therapies for the treatment of solid tumors and hematological malignancies. Astex is a member of the Otsuka group of companies. The group also includes Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Taiho Oncology, Inc. Subject to regulatory approvals, Astex’s products will be commercialized in the U.S. and Canada by Taiho subsidiaries, and in the rest of the world by Otsuka subsidiaries.
 
Astex, the Astex logo, Taiho Oncology, the Taiho Oncology logo and INQOVI are registered trademarks of Otsuka Holdings Co., Ltd. or its subsidiaries.

NCCN® and the NCCN Guidelines® are registered trademarks of National Comprehensive Cancer Network.

MEDIA CONTACTS
Taiho Oncology:

Judy Kay Moore
(+1) 574-526-2369
jumoore@taihooncology.com

Astex Pharmaceuticals:

Martin Buckland
Astex Pharmaceuticals, Inc.
(+1) 925-560-0100
martin.buckland@astx.com

###

1 NCCN Clinical Practice Guidelines in Oncology. Myelodysplastic Syndromes. Version 1.2023. Last updated September 12, 2022. Accessed November 28, 2022.

2 INQOVI Prescribing Information. www.inqovi.com/pi. Accessed November 15, 2022.

3 Garcia-Manero G. Myelodysplastic syndromes: 2015 update on diagnosis, risk-stratification and management. Am J Hematol. 2015; 90(9): 831-841.

4 Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: Incidence and survival in the United States. Cancer. 2007; 109(8): 1536–1542.

5 Cogle C. Incidence and burden of the myelodysplastic syndromes. Curr Hematol Malig Rep. 2015; 10(3): 272-281.

6 Shukron O, Vainstein V, Kündgen A, Germing U, Agur Z. Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database. Am J Hematol. 2012; 87: 853–860.

7 What are the key statistics about chronic myelomonocytic leukemia? American Cancer Society Web site. https://www.cancer.org/cancer/chronic-myelomonocytic-leukemia/about/key-statistics.html. Accessed November 15, 2022.

8 About chronic myelomonocytic leukemia (CMML). Cancer Research UK Web site. https://www.cancerresearchuk.org/about-cancer/other-conditions/chronic-myelomonocytic-leukaemia-cmml/about. Accessed November 15, 2022.

• The phase 3 ASCERTAIN – AML clinical study of decitabine and cedazuridine, administered orally as a fixed-dose combination (ASTX727), in adult patients with AML not candidates for standard induction chemotherapy demonstrated decitabine exposure equivalence of total 5-day dosing between oral ASTX727 and intravenous (IV) decitabine
• Data from the study will be presented on June 10, 2022, as part of the annual meeting of the European Hematology Association (EHA) in Vienna, Austria
• Astex plans to file a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA)
• ASTX727 is the only oral hypomethylating agent with equivalent exposure to its parenterally administered form

Pleasanton, CA, May 12 – Astex Pharmaceuticals, Inc. announces today top-line results from the ASCERTAIN phase 3 study evaluating oral decitabine and cedazuridine fixed-dose combination (ASTX727 or DEC-C) tablets versus IV decitabine in adults with AML who are not candidates to receive standard induction chemotherapy.

The study met its primary endpoint of decitabine exposure equivalence of 5-day dosing between orally administered ASTX727 and intravenous (IV) decitabine as per the protocol analysis plan with a high degree of confidence.  Safety observations were similar to those observed with IV decitabine.

The full data will be presented on June 10 as part of EHA2022. Astex plans to file a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) and similar applications in other countries where IV decitabine is indicated for the treatment of AML.

“We are delighted with the outcome of the ASCERTAIN – AML trial, and the demonstration that the fixed-dose oral combination of decitabine and cedazuridine provides exposure equivalence to IV decitabine in the AML population,” said Harold Keer, MD, PhD, chief medical officer of Astex Pharmaceuticals, Inc.  “Subject to regulatory review and approvals, ASTX727 could bring a new treatment option to patients with AML who are not candidates to receive standard induction chemotherapy. The ASCERTAIN – AML study was conducted during the height of the COVID-19 pandemic, and this experience helped to highlight the potential advantage of an orally administered therapy. We are extremely grateful to all the patients, caregivers, partner research and manufacturing organizations, as well as the healthcare professionals who contributed to this effort.”

“Parenterally administered hypomethylating agents have been a cornerstone of the treatment of AML patients who are not candidates to receive standard induction chemotherapy for over 10 years,” said Professor Klaus Geissler MD, principal investigator of the ASCERTAIN – AML phase 3 study and head of the Fifth Medical Department, Clinic Hietzing Hospital, Vienna, Austria. “Oral ASTX727 may deliver a treatment alternative for patients with AML which potentially reduces the number of office visits and offers an option for patients to take their medication from the convenience and comfort of their homes.”

Based on the data from the ASCERTAIN clinical program, the oral decitabine and cedazuridine fixed-dose combination is also being investigated in combination with other agents in hematological malignancies. The first of these studies is investigating the all-oral combination of decitabine and cedazuridine with venetoclax for the treatment of AML.

Oral decitabine and cedazuridine fixed-dose combination is approved as INQOVI^® in the U.S. and Canada for the treatment of intermediate and high-risk myelodysplastic syndromes (MDS), including chronic myelomonocytic leukemia (CMML) and is the only approved oral hypomethylating agent that has demonstrated equivalent exposure to its IV form.

Commercialization of INQOVI in the U.S. and Canada for the above indication is conducted by Taiho Oncology, Inc., and by Taiho Pharma Canada, Inc., respectively.  Astex, Otsuka and Taiho are all members of the Otsuka group of companies.

ABOUT THE ASCERTAIN – AML CLINICAL STUDY¹

The ASCERTAIN – AML clinical trial was designed as a randomized crossover study comparing oral decitabine (35mg) and cedazuridine (100mg) fixed-dose combination tablet given once daily for 5 days on a 28-day cycle to IV decitabine (20mg/m²) administered as a daily 1-hour infusion for 5 days on a 28-day cycle, in the first 2 cycles in AML patients who were unfit to receive intensive chemotherapy. Patients continued to receive oral decitabine and cedazuridine from cycle 3 onwards. The primary endpoint for the study was total 5-day decitabine area-under-the-curve (AUC) equivalence of oral decitabine and cedazuridine and IV decitabine.  See: https://www.clinicaltrials.gov/ct2/show/NCT03306264

ABOUT DECITABINE AND CEDAZURIDINE FIXED-DOSE COMBINATION (ASTX727)

ASTX727 is an orally administered, fixed dose combination of the approved anti-cancer DNA hypomethylating agent, decitabine, together with cedazuridine,² an inhibitor of cytidine deaminase.³ By inhibiting cytidine deaminase in the gut and the liver, ASTX727 is designed to allow for oral delivery of decitabine over 5 days in a given cycle to achieve comparable systemic exposure to IV decitabine  administered over 5 days.

ASTX727 has been evaluated in a phase 1/2 pharmacokinetics-guided dose escalation and dose confirmation study, and a phase 3 exposure equivalence study in patients with MDS and CMML. The phase 1 and phase 2 clinical study results have been published in Lancet Haematology⁴ and Blood,⁵ respectively, and the phase 3 results have been presented at the American Society of Hematology Annual Meeting in December 2019⁶ and the International Congress on Myelodysplastic Syndromes in September 2021.⁷

Astex is also expanding the evaluation of decitabine – cedazuridine combinations through a program of investigator-sponsored trials.

ASTX727 is an investigational compound and is not currently approved in any country other than the U.S., Canada, and Australia.

The EHA abstract can be downloaded from the EHA website at:  https://library.ehaweb.org/eha/2022/eha2022-congress/357436.

Learn more about INQOVI at https://www.inqovi.com

INDICATIONS

In the U.S., INQOVI (decitabine and cedazuridine) is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.⁸

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Myelosuppression: Fatal and serious myelosuppression can occur with INQOVI. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%. Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrile neutropenia) is the most frequent cause of INQOVI dose reduction or interruption, occurring in 36% of patients. Permanent discontinuation due to myelosuppression (febrile neutropenia) occurred in 1% of patients. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.

Fatal and serious infectious complications can occur with INQOVI. Pneumonia occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsis occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1%.

Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors, and anti‑infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.

Embryo-Fetal Toxicity: INQOVI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise patients to use effective contraception during treatment with INQOVI and for 6 months (females) or 3 months (males) after last dose.

ADVERSE REACTIONS

Serious adverse reactions in > 5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse reactions included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and one case each of cerebral hemorrhage and sudden death.

The most common adverse reactions (≥ 20%) were fatigue (55%), constipation (44%), hemorrhage (43%), myalgia (42%), mucositis (41%), arthralgia (40%), nausea (40%), dyspnea (38%), diarrhea (37%), rash (33%), dizziness (33%), febrile neutropenia (33%), edema (30%), headache (30%), cough (28%), decreased appetite (24%), upper respiratory tract infection (23%), pneumonia (21%), and transaminase increased (21%). The most common Grade 3 or 4 laboratory abnormalities (>50%) were leukocytes decreased (81%), platelet count decreased (76%), neutrophil count decreased (71%), and hemoglobin decreased (55%).

USE IN SPECIFIC POPULATIONS

Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with INQOVI and for 2 weeks after the last dose.

Renal Impairment: No dosage modification of INQOVI is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] of 30 to 89 mL/min based on Cockcroft-Gault). Due to the potential for increased adverse reactions, monitor patients with moderate renal impairment (CLcr 30 to 59 mL/min) frequently for adverse reactions. INQOVI has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min) or end-stage renal disease (ESRD: CLcr <15 mL/min).

Please see the accompanying Full Prescribing Information.

ABOUT ACUTE MYELOID LEUKEMIA (AML)

AML is the most common form of acute leukemia in adults.⁹ An estimated 20,050 new cases of AML are projected to be diagnosed in the U.S. in 2022¹⁰ and an estimated 11,540 patients are projected to die from AML in the US in 2022.^10. Although 60 to 80 percent of AML patients less than 60 years of age may achieve a complete response (CR) with standard intensive induction chemotherapy,¹¹ the outlook for patients 60 years of age or more is significantly worse, with response rates less than 50 percent, cure rates following transplant remaining at less than 10 percent and a median survival of less than one year.^11-13. These figures have not significantly improved during the last three decades. These patients have few therapeutic options available.^14-15. Effective, less toxic therapies are needed for the treatment of AML, particularly for elderly patients where comorbidities and other consequences of aging may often render them ineligible to receive intensive remission induction chemotherapy, thus denying them a potentially curative transplant.¹³

ABOUT ASTEX PHARMACEUTICALS AND OTSUKA PHARMACEUTICAL

Astex Pharmaceuticals, Inc. is committed to the fight against cancer. Astex is developing a proprietary pipeline of novel therapies for the treatment of solid tumors and hematological malignancies. Astex is a member of the Otsuka group of companies. The group also includes Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Taiho Oncology, Inc. Subject to regulatory approvals, Astex’s products will be commercialized in the U.S. and Canada by Taiho subsidiaries, and in the rest of the world by Otsuka subsidiaries.

Otsuka Pharmaceutical is a global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide. Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.

For more information about Astex Pharmaceuticals, please visit: https://www.astx.com

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

Astex, the Astex logo, Otsuka, and INQOVI are registered trademarks of Otsuka Holdings Co., Ltd. or its subsidiaries.

Contact Details

Martin Buckland

President & Chief Corporate Officer

Astex Pharmaceuticals, Inc.

Pleasanton, CA 94588, USA

Tel: +1-925-560-0100

Email: info@astx.com

References

1. Geissler K, Koristek Z, Castillo T, et al. Pharmacokinetic Exposure Equivalence and Preliminary Efficacy and Safety from a Randomized Cross Over Phase 3 Study of an Oral Hypomethylating Agent DEC-C Compared to IV Decitabine in AML Patients. 2022; HemaSphere 2022; 6:S3. Abstract P573.
2. Oganesian A, Redkar S, Taverna P, Choy G, Joshi-Hangal R, Azab M. Preclinical data in cynomolgus (cyn) monkeys of ASTX727, a novel oral hypomethylating agent (HMA) composed of low-dose oral decitabine combined with a novel cytidine deaminase inhibitor (CDAi) E7727 [ASH abstract 2526]. Blood 2013;122(21):2526.
3. Ferraris D, Duvall B, Delahanty G, et al. Design, synthesis, and pharmacological evaluation of fluorinated tetrahydrouridine derivatives as inhibitors of cytidine deaminase. J Med Chem 2014; 57:2582-2588. doi:10.1021/jm401856k.
4. Savona MR, Odenike O, Amrein PC, Steensma DP, DeZern AE, Michaelis LC, et al. An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Lancet Haematol. 2019;6(4):e194-e203. doi:10.1016/S2352-3026(19)30030-4.
5. Garcia-Manero G, Griffiths EA, Steensma DP, et al. Oral cedazuridine/decitabine: a phase 2, pharmacokinetic/pharmacodynamic, randomized, crossover study in MDS and CMML [published online ahead of print, 2020 Apr 13]. Blood. 2020; blood.2019004143. doi:10.1182/blood.2019004143.
6. Garcia-Manero G, McCloskey J, Griffiths EA, et al. Pharmacokinetic Exposure Equivalence and Preliminary Efficacy and Safety from a Randomized Crossover Phase 3 Study (ASCERTAIN study) of an Oral Hypomethylating Agent ASTX727 (cedazuridine/decitabine) Compared to IV Decitabine. 2019; 134(Supplement_1): 846. doi.org/10.1182/blood-2019-122980.
7. Savona M, McCloskey J, Griffiths E, et al. Current treatment options – hypomethylating agents: prolonged survival observed in 133 MDS patients treated with oral decitabine/cedazuridine. Leukemia Research, Volume 108, Supplement, 2021. org/10.1016/j.leukres.2021.106681.47.
8. INQOVI Prescribing Information. inqovi.com/pi
9. De Kouchkovsky I, Abdul-Hay M. ‘Acute myeloid leukemia: a comprehensive review and 2016 update’. Blood Cancer J. 2016;6(7):e441. Published 2016 Jul 1. doi:10.1038/bcj.2016.50.
10. American Cancer Society. Key Statistics for Acute Myeloid Leukemia 2022 [Available from: https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html.
11. Dohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447. doi:10.1182/blood-2016-08-733196.
12. Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. [published correction appears in J Clin Oncol. 2011 Jun 1;29(16):2293]. J Clin Oncol. 2011;29(5):487-494. doi:10.1200/JCO.2010.30.1820.
13. Dombret H, Gardin C. An update of current treatments for adult acute myeloid leukemia. Blood. 2016;127(1):53-61. doi:10.1182/blood-2015-08-604520.
14. Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94(7):1127-1138. doi:10.1007/s00277-015-2351-x.
15. Wang R, Zeidan AM, Halene S, et al. Health Care Use by Older Adults With Acute Myeloid Leukemia at the End of Life. J Clin Oncol. 2017;35(30):3417-24. doi:10.1200/JCO.2017.72.7149.

• Study achieved median overall survival of 31.7 months
• Updated efficacy data demonstrated an overall response rate of 62%, with 22% of patients achieving a complete response
• INQOVI is the only oral hypomethylating agent with equivalent exposure to its intravenous (IV) form

Pleasanton, CA, September 23, 2021. Astex Pharmaceuticals, Inc., a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan, today announced updated clinical data, including median overall survival (mOS), from the ASCERTAIN phase 3 trial of INQOVI®, the company’s orally administered fixed-dose combination of decitabine and cedazuridine (ASTX727 or DEC-C) in adults with intermediate and high-risk myelodysplastic syndromes (MDS) including chronic myelomonocytic leukemia (CMML). mOS was 31.7 months.

The data were featured in a presentation given today at the 16^th International Congress on Myelodysplastic Syndromes in Toronto, Canada, by Michael Savona, MD, Professor of Medicine and Cancer Biology, Department of Internal Medicine at Vanderbilt University School of Medicine, Tenn., on behalf of the study investigators.

The ASCERTAIN clinical trial was designed as a randomized crossover study comparing oral decitabine (35mg) and cedazuridine (100mg) fixed-dose combination tablet given once daily for 5 days on a 28-day cycle to IV decitabine (20mg/m²) administered as a daily 1-hour IV infusion for 5 days on a 28-day cycle, in the first 2 cycles. Patients continued to receive oral decitabine and cedazuridine from Cycle 3 onwards. The primary endpoint data for the study of total 5-day decitabine area-under-the-curve (AUC) equivalence of oral decitabine and cedazuridine and IV decitabine was previously presented at the American Society of Hematology Annual Meeting in December 2019.¹ The oral/IV decitabine 5-day AUC was 98.9% with a 90% Confidence Interval between 92.7% and 105.6%.

Safety findings from the study were similar to those anticipated with IV decitabine, with incidence of cytopenias slightly higher with INQOVI during Cycle 1 compared to IV decitabine. The most common adverse events (AEs) of thrombocytopenia, neutropenia, and anemia were consistent with expected AEs with parenteral hypomethylating agent treatment.

In the more mature data set used to evaluate overall survival, the complete response (CR) rate for evaluable patients was 22%, with an overall response rate (CR + Partial Response + Marrow CR + Hematological Improvement) of 62%.

“Taken together, the ASCERTAIN phase 3 study data support considerable therapeutic utility of oral decitabine and cedazuridine in the treatment of patients with MDS and CMML,” said Co-Principal Investigator of the ASCERTAIN phase 3 study, Michael Savona, MD. “The fixed-dose combination of decitabine and cedazuridine is the only available oral DNA methyltransferase inhibitor / hypomethylating agent that has demonstrated equivalent exposure to an IV form. The median overall survival data from this study makes oral decitabine and cedazuridine an alternative option to parenteral administration of decitabine for patients with these diseases.”

Added Timothy Whitten, president and CEO of Taiho Oncology, Inc., Astex’s commercialization partner for INQOVI in the United States: “We are encouraged by data from the ASCERTAIN trial that continue to show oral decitabine and cedazuridine is a promising treatment option for patients living with MDS and CMML. Importantly, patients can benefit from the convenience of an at-home hypomethylating agent treatment and potentially reduce the number of office visits and associated travel.”

Based on the data from the ASCERTAIN clinical program, INQOVI is being investigated in combination with other agents in hematological malignancies, according to Harold Keer, MD, PhD, chief medical officer of Astex Pharmaceuticals, Inc. “The first of these studies is investigating the all-oral combination of decitabine and cedazuridine with venetoclax for the treatment of AML. We are extremely grateful to all the patients, caregivers, partner research and manufacturing organizations, as well as the healthcare professionals who have contributed to the clinical development program of oral decitabine and cedazuridine.”

INQOVI is an orally administered, fixed-dose combination of the approved anti-cancer DNA hypomethylating agent, decitabine, together with cedazuridine,² an inhibitor of cytidine deaminase.³ By inhibiting cytidine deaminase in the gut and the liver, INQOVI is designed to allow for oral delivery of decitabine over five days in a given cycle to achieve comparable systemic exposure to IV decitabine. The phase 1 and phase 2 clinical study results have been published in Lancet Haematology⁴ and Blood,⁵ respectively.

INQOVI was approved in July 2020 by the U.S. Food and Drug Administration (FDA) and by Health Canada. INQOVI is the first and only oral hypomethylating agent approved by the FDA and by Health Canada for the treatment of adults with intermediate and high-risk MDS including CMML.⁶

Commercialization of INQOVI in the U.S. and Canada is conducted by Taiho Oncology, Inc. and Taiho Pharma Canada, Inc., respectively. Astex, Otsuka and Taiho are all members of the Otsuka group of companies.

The presentation can be downloaded from the Astex website at: https://stagin.astx.co.uk/ASTX727 – International MDS Symposium September 2021

Learn more about INQOVI at https://www.inqovi.com

INDICATIONS

INQOVI (decitabine and cedazuridine) is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.⁶

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Myelosuppression: Fatal and serious myelosuppression can occur with INQOVI. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%. Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrile neutropenia) is the most frequent cause of INQOVI dose reduction or interruption, occurring in 36% of patients. Permanent discontinuation due to myelosuppression (febrile neutropenia) occurred in 1% of patients. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.

Fatal and serious infectious complications can occur with INQOVI. Pneumonia occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsis occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1%.

Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors, and anti‑infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.

Embryo-Fetal Toxicity: INQOVI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise patients to use effective contraception during treatment with INQOVI and for 6 months (females) or 3 months (males) after last dose.

ADVERSE REACTIONS

Serious adverse reactions in > 5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse reactions included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and one case each of cerebral hemorrhage and sudden death.

The most common adverse reactions (≥ 20%) were fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and transaminase increased. The most common Grade 3 or 4 laboratory abnormalities (>50%) were leukocytes decreased, platelet count decreased, neutrophil count decreased, and hemoglobin decreased.

USE IN SPECIFIC POPULATIONS

Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with INQOVI and for at least 2 weeks after the last dose.

Renal Impairment: No dosage modification of INQOVI is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] of 30 to 89 mL/min based on Cockcroft-Gault). Due to the potential for increased adverse reactions, monitor patients with moderate renal impairment (CLcr 30 to 59 mL/min) frequently for adverse reactions. INQOVI has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min) or end-stage renal disease (ESRD: CLcr <15 mL/min).

Please see the accompanying Full Prescribing Information.

About Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. U.S. incidence of MDS is estimated to be 10,000 cases per year, although the condition is thought to be under-diagnosed.^7,8 The prevalence has been estimated to be from 60,000 to 170,000 in the U.S.⁹ MDS may evolve into acute myeloid leukemia (AML) in one-third of patients.¹⁰ The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML.

CMML is a clonal hematopoietic malignancy characterized by accumulation of abnormal monocytes in the bone marrow and in blood. The incidence of CMML in the U.S. is approximately 1,100 new cases per year,¹¹ and CMML may transform into AML in 15% to 30% of patients.¹²

About Astex, Taiho, and Otsuka

Astex Pharmaceuticals, Inc. (“Astex”) is committed to the fight against cancer. Astex is developing a proprietary pipeline of novel therapies for the treatment of solid tumors and hematological malignancies. Astex is a member of the Otsuka group of pharmaceutical companies. The group also includes Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Taiho Oncology, Inc. Subject to regulatory approvals, Astex’s products will be commercialized in the U.S. and Canada by Taiho subsidiaries, and in the rest of the world by Otsuka subsidiaries.

The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development of orally administered anti-cancer agents and markets these medicines for a range of tumor types in the U.S. Taiho Oncology’s growing pipeline of antimetabolic and selectively targeted anti-cancer agents are led by a world-class clinical development organization. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company’s European and Canadian operations, which are located in Zug, Switzerland and Oakville, Ontario, Canada.

Otsuka Pharmaceutical is a global healthcare company with the corporate philosophy: “Otsuka–people creating new products for better health worldwide.” Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.

For more information about Astex Pharmaceuticals, Inc. please visit: https://www.astx.com

For more information about Otsuka Pharmaceutical, please visit: https://www.otsuka.co.jp/en/

For more information about Taiho Oncology, please visit: https://www.taihooncology.com/

 Contact Details

Martin Buckland
President & Chief Corporate Officer
Astex Pharmaceuticals, Inc.
4420 Rosewood Drive, Suite 200
Pleasanton, CA 94588, USA
Tel: +1-925-560-0100
Email: info@astx.com
 

References

1. Garcia-Manero G, McCloskey J, Griffiths EA, et al. Pharmacokinetic exposure equivalence and preliminary efficacy and safety from a randomized cross over Phase 3 study (ASCERTAIN study) of an oral hypomethylating agent ASTX727 (cedazuridine/decitabine) compared to IV decitabine. 2019; 134(Supplement_1).
2. Oganesian A, Redkar S, Taverna P, Choy G, Joshi-Hangal R, Azab M. Preclinical data in cynomolgus (cyn) monkeys of ASTX727, a novel oral hypomethylating agent (HMA) composed of low-dose oral decitabine combined with a novel cytidine deaminase inhibitor (CDAi) E7727 [ASH Abstract]. 2013; 122(21): Abstract 2526.
3. Ferraris D, Duvall B, Delahanty G, Mistry B, Alt, J, Rojas C, et al. Design, synthesis, and pharmacological evaluation of fluorinated tetrahydrouridine derivatives as inhibitors of cytidine deaminase. J Med Chem. 2014; 57: 2582-2588.
4. Savona MR, Odenike O, Amrein PC, Steensma DP, DeZern AE, Michaelis LC, et al. An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Lancet Haematol [Internet]. 2019; 6(4): e194-e203.
5. Garcia-Manero G, Griffiths EA, Steensma DP, et al. Oral cedazuridine/decitabine: a phase 2, pharmacokinetic/pharmacodynamic, randomized, crossover study in MDS and CMML [published online ahead of print, 2020 Apr 13]. Blood. 2020; blood.2019004143. doi:10.1182/blood.2019004143.
6. INQOVI Prescribing Information. inqovi.com/pi
7. Garcia-Manero G. Myelodysplastic syndromes: 2015 update on diagnosis, risk-stratification and management. Am J Hematol. 2015; 90(9): 831-841.
8. Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: Incidence and survival in the United States. 2007; 109(8): 1536–1542.
9. Cogle C. Incidence and burden of the myelodysplastic syndromes. Curr Hematol Malig Rep. 2015; 10(3): 272-281.
10. Shukron O, Vainstein V, Kündgen A, Germing U, Agur Z. Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database. Am J Hematol. 2012; 87: 853–860.
11. What are the key statistics about chronic myelomonocytic leukemia? American Cancer Society Web site. https://www.cancer.org/cancer/chronic-myelomonocytic-leukemia/about/key-statistics.html. Accessed 03 August 2021.
12. About chronic myelomonocytic leukemia (CMML). Cancer Research UK Web site. https://www.cancerresearchuk.org/about-cancer/other-conditions/chronic-myelomonocytic-leukaemia-cmml/about. Accessed 03 August 2021.

INQ-PM-US-0362  09/21

• NCI has announced availability to investigators of oral decitabine and cedazuridine tablets for clinical and nonclinical study proposals under the CRADA
• The collaboration is intended to study oral decitabine and cedazuridine tablets in a range of tumor types

Pleasanton, CA, – October 28th, 2020. ­­– Astex Pharmaceuticals, Inc., a wholly owned subsidiary of Otsuka Pharmaceutical Co., Ltd., based in Tokyo, Japan, today announces it has entered into a Cooperative Research and Development Agreement with the U.S. National Cancer Institute, part of National Institutes of Health. The agreement calls for a range of new clinical and translational studies of oral decitabine and cedazuridine tablets as an anticancer agent to be conducted in collaboration with Astex.  The NCI’s Cancer Therapy Evaluation Program (CTEP) has announced they are accepting Letters of Intent for evaluation of oral decitabine and cedazuridine tablets in hematological malignancies and solid tumors, including in combination with other investigational agents. Study proposals will be reviewed by CTEP and by Astex.

On July 7th, 2020, Astex’s hypomethylating agent INQOVI® (decitabine and cedazuridine) 35mg/100mg tablets, for oral use, was approved simultaneously by the U.S. FDA and by Health Canada for the treatment of intermediate- and high-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) patients in the U.S. and Canada, respectively.

“Oral decitabine and cedazuridine tablets offer a new treatment option for patients with MDS and CMML,” said Mohammad Azab, president and chief medical officer of Astex. “We are delighted to be entering into this collaboration with NCI to investigate and broaden the evaluation of the clinical potential of oral decitabine and cedazuridine. We look forward to working with investigators to study how oral targeted therapies might work in combination to treat patients with leukemia and solid tumors.”

The initial study being conducted under the CRADA will investigate the combination of oral decitabine and cedazuridine tablets with venetoclax in the treatment of acute myeloid leukemia. The CRADA will also include oral decitabine and cedazuridine tablets in the NCI myeloMATCH master trial aimed at evaluating therapies for the treatment of myeloid malignancies. Astex will provide funding, study drug, and personnel to support the proposed studies.

About INQOVI (decitabine and cedazuridine) 35mg/100mg tablets
Indications and Important Safety Information

INDICATIONS

In the U.S. and Canada, INQOVI is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Myelosuppression
Fatal and serious myelosuppression can occur with INQOVI. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%. Myelosuppression (thrombocytopenia, neutropenia, anemia, and febrile neutropenia) is the most frequent cause of INQOVI dose reduction or interruption, occurring in 36% of patients. Permanent discontinuation due to myelosuppression (febrile neutropenia) occurred in 1% of patients. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.

Fatal and serious infectious complications can occur with INQOVI. Pneumonia occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsis occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1%.

Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors and anti‑infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.

Embryo-Fetal Toxicity
INQOVI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise patients to use effective contraception during treatment and for 6 months (females) or 3 months (males) after last dose.

ADVERSE REACTIONS
Serious adverse reactions in > 5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse reactions included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and one case each of cerebral hemorrhage and sudden death.

The most common adverse reactions (≥ 20%) were fatigue (55%), constipation (44%), hemorrhage (43%), myalgia (42%), mucositis (41%), arthralgia (40%), nausea (40%), dyspnea (38%), diarrhea (37%), rash (33%), dizziness (33%), febrile neutropenia (33%), edema (30%), headache (30%), cough (28%), decreased appetite (24%), upper respiratory tract infection (23%), pneumonia (21%), and transaminase increased (21%). The most common Grade 3 or 4 laboratory abnormalities (≥ 50%) were leukocytes decreased (81%), platelet count decreased (76%), neutrophil count decreased (71%), and hemoglobin decreased (55%).

USE IN SPECIFIC POPULATIONS
Lactation

Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with INQOVI and for at least 2 weeks after the last dose.

Renal Impairment
No dosage modification of INQOVI is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] of 30 to 89 mL/min based on Cockcroft-Gault). Due to the potential for increased adverse reactions, monitor patients with moderate renal impairment (CLcr 30 to 59 mL/min) frequently for adverse reactions. INQOVI has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min) or end-stage renal disease (ESRD: CLcr <15 mL/min).

Please see full Prescribing Information.

INQOVI is being commercialized by Taiho Oncology, Inc. and Taiho Pharma Canada, Inc. in the U.S. and Canada, respectively. INQOVI is not approved in any other market worldwide. Taiho and Astex are members of the Otsuka group of companies. INQOVI® is a registered trademark of Otsuka Pharmaceutical Co., Ltd.

About Astex Pharmaceuticals, Otsuka Pharmaceutical and Taiho Oncology

Astex Pharmaceuticals, Inc. is a leader in innovative drug discovery and development, committed to the fight against cancer.  Astex is developing a proprietary pipeline of novel therapies and has multiple partnered products in development under collaborations with leading pharmaceutical companies.  Astex is a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan.

Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: “Otsuka–people creating new products for better health worldwide.” Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.

Taiho Oncology, Inc., is a subsidiary of Taiho Pharmaceutical Co., Ltd. and an indirect subsidiary of Otsuka Holdings Co., Ltd. Taiho has established a world-class clinical development organization that works urgently to develop innovative cancer treatments and has built a commercial business in the U.S. Taiho has an oral oncology pipeline consisting of both novel antimetabolic agents and selectively targeted agents.

For more information about Astex Pharmaceuticals, Inc. please visit: https://stagin.astx.co.uk

For more information about Otsuka Pharmaceutical, please visit: https://www.otsuka.co.jp/en/

For more information about Taiho Pharmaceutical, please visit: https://www.taihooncology.com/

Contact Details

Martin Buckland
Chief Corporate Officer
Astex Pharmaceuticals, Inc.
4420 Rosewood Drive, Suite 200
Pleasanton 94588, CA, USA
Tel: +1-925-560-2857
Email: info@astx.com

INQ-PM-US-0128