Otsuka and Astex announce that the European Commission has approved INAQOVI® (oral decitabine and cedazuridine) for the treatment of adults with newly diagnosed acute myeloid leukaemia

LONDON, UK, and PLEASANTON, CA, USA, 19th September 2023 – Otsuka Pharmaceutical Europe Ltd. (Otsuka) and Astex Pharmaceuticals, Inc. (Astex) today announce that the European Commission (EC) has approved INAQOVI® (oral decitabine and cedazuridine) as monotherapy for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for standard induction chemotherapy. The EC decision applies to the European Economic Area (EEA), which includes the EU member states, Iceland, Liechtenstein and Norway. INAQOVI® is the first and only oral hypomethylating agent licensed in the EEA in this patient population.

The EC approval is based on the results from the Phase 3 ASCERTAIN clinical trial investigating the pharmacokinetic exposure equivalence of the novel oral fixed-dose combination versus intravenous (IV) decitabine in AML patients1. The ASCERTAIN study met its primary endpoint, with the orally administered decitabine and cedazuridine fixed-dose combination showing pharmacokinetic exposure equivalence to a standard 5-day regimen of IV decitabine using a two-cycle, cross-over study design. Safety findings for the fixed-dose combination of decitabine and cedazuridine were generally consistent with those anticipated for IV decitabine1.

The current treatment options for adults with AML range from hospital-administered IV chemotherapy infusions or, for those patients not eligible for chemotherapy, regimens based on parenterally administered hypomethylating agents, with treatment cycles typically extending for 5-7 days2. Fatigue can significantly restrict daily activities and impact a patient’s quality of life3. INAQOVI® may provide both patients and physicians with an oral treatment option in this patient population.

On 10th June 2022, the European Medicines Agency (EMA) agreed to a Paediatric Investigation Plan for the oral decitabine and cedazuridine fixed-dose combination, representing an important milestone for the prospect of furthering clinical studies in children with AML.

About decitabine and cedazuridine fixed-dose combination (INAQOVI®)

INAQOVI® is an orally administered, fixed-dose combination of the approved hypomethylating agent (HMA), decitabine (35 mg), together with cedazuridine (100 mg), an inhibitor of cytidine deaminase4-6. By inhibiting cytidine deaminase in the gut and liver, the fixed-dose combination is designed to allow for oral daily administration of decitabine over 5 days in a given cycle to achieve comparable systemic exposure to IV decitabine administered with the same dosing regimen7.

In the Phase 3 ASCERTAIN study, a total of 89 AML patients were randomised 1:1 to receive INAQOVI® (35 mg decitabine and 100 mg cedazuridine) orally in Cycle 1 and decitabine (20 mg/m2) intravenously in Cycle 2 (n=44) or the reverse sequence (n=45). Both INAQOVI® and IV decitabine were administered once daily on Days 1 through 5 of the 28-day cycle. Starting with Cycle 3, all patients received INAQOVI® orally once daily on Days 1 through 5 of each 28-day cycle until disease progression, death, or unacceptable toxicity6.

Primary endpoint results showed that patients receiving INAQOVI® achieved pharmacokinetic exposure equivalence of 99.64% (90% CI: 91.23, 108.8) to IV decitabine given at 20 mg/m2 for 5-days with a similar pharmacodynamic activity. Secondary findings showed a Median Overall Survival of 7.9 months (95% CI: 5.9, 13.0) and a Complete Response rate of 21.8% at 7.95 months median follow up1.

The most common adverse drug reaction (≥ 20%) was thrombocytopenia. The most common serious adverse reactions (≥ 20%) were febrile neutropenia and pneumonia. Permanent discontinuation occurred in 14% of patients while on treatment. The most frequent adverse reaction resulting in permanent discontinuation was pneumonia (5%)6.

 About acute myeloid leukaemia (AML)

AML is the most common form of acute leukaemia in adults8. The median age at diagnosis is approximately 70 years2. Within Europe, the incidence of AML is increasing, this may be attributed to the ageing population; AML incidence in Europe has risen from 3.48 in 1976 to 5.06 patients per 100,000 population in 20132. Across Europe and all age groups, AML is notably more common in males than in females2. The outlook for patients diagnosed with AML has improved over time due to improved care and treatment, however between the years of 2000 and 2007, 5-year survival for patients was just 17%2.

About Otsuka

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 products, focusing on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health. In pharmaceuticals, Otsuka is a leader in the challenging area of mental health and has research programmes in several under-addressed diseases including tuberculosis, a significant global public health issue.

Otsuka Europe employs around 550 people and focuses on psychiatric and neurologic disorders, infectious disease, nephrology, oncology, and digital medicines.

Otsuka Pharmaceutical Europe Ltd. is a part of Otsuka Pharmaceutical Company, Ltd., a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan.

The Otsuka group of companies employed 47,000 people worldwide with consolidated sales of approximately €12.4 billion and a spend of €1.67 billion on research and development in 2022. For further information on Otsuka, please visit www.otsuka-europe.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 tumours and haematological 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 commercialised in the U.S. and Canada by Taiho subsidiaries, and in the rest of the world by Otsuka subsidiaries.

MEDIA CONTACTS

 OTSUKA PHARMACEUTICAL EUROPE LTD.

Alison Ross
Otsuka Pharmaceutical Europe Ltd.
+44 (0)7768 337 128
ARoss@Otsuka-Europe.com

 

ASTEX PHARMACEUTICALS, INC.

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

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

 References

  1. Geissler K, Koristek Z, Bernal del Castillo T, et al. Pharmacokinetic exposure equivalence and preliminary efficacy and safety from a randomized crossover Phase 3 study of an oral hypomethylating agent, ASTX727 (DEC-C), compared to IV decitabine in AML patients. Poster presented at the European Hematology Association Congress; 9–12 June 2022; Vienna, Austria. Abstract P573.
  2. Heuser M, Ofran Y, Boissel N, et al. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(6):697–712.
  3. No authors listed. Benefits of AML Maintenance Therapy Extend to Quality of Life and Hospitalization. Oncologist. 2021;26 (Suppl 1):S11–S12.
  4. Oganesian A, Redkar S, Taverna P, et al. Preclinical Data in Cynomolgus Monkeys of ASTX727, a novel oral hypomethylating agent (HMA) composed of low-dose oral decitabine combined with a novel Cytidine Deaminase Inhibitor (CDAi) E7727. Poster presented at the American Society of Hematology Annual Meeting; 7–10 December 2013; New Orleans, LA. Abstract 2526.
  5. 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(6):2582–2588.
  6. INAQOVI Summary of Product Characteristics (Europe), September 2023.
  7. INQOVI Product Monograph (Canada), March 2022.
  8. De Kouchkovsky I, Abdul-Hay M. ‘Acute myeloid leukemia: a comprehensive review and 2016 update’. Blood Cancer J. 2016;6(7):e441.

 

Astex Expands Drug Discovery Collaboration With MSD

Cambridge, UK, 8 August 2023, Astex Pharmaceuticals (UK) (“Astex”), a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system, today announced an exclusive worldwide research collaboration and license agreement with MSD (Merck & Co., Inc., Rahway, N.J., USA).  The goal of the collaboration is to identify small molecule candidates with activity towards a tumour suppressor protein for the treatment of cancer.

“Astex is applying its fragment-based drug discovery capability to design and generate small molecule modulators tailored to a wide range of potentially important therapeutic targets,” said Harren Jhoti, president and CEO of Astex.  “This new alliance builds on our existing productive collaboration and allows us to combine our expertise and assets with MSD’s wide-ranging oncology capabilities.”

Under the terms of the agreement, Astex will apply its fragment-based drug discovery platform to develop compounds targeting multiple forms of the p53 tumour suppressor protein and provide MSD with lead compounds for further optimization and preclinical development.  MSD is granted an exclusive global license to research, develop, and commercialise candidates arising under the collaboration.  Astex will receive an upfront payment of $35 million and is eligible for milestone payments associated with the achievement of preclinical, clinical, regulatory and sales milestones, totalling approximately $500 million per program, as well as tiered royalties on sales of any products arising from the collaboration.  MSD will assume responsibility for funding all future research and development of lead candidates as well as commercialisation of products globally.

“At MSD we are committed to driving innovation with the goal of improving outcomes for patients with cancer,” said George Addona, senior vice president discovery and translational medicine, MSD. “We look forward to building on our collaboration with the Astex team to advance this potentially impactful area of oncology research.”

-ENDS-

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. Astex is a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan.

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

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

CONTACTS

At Astex Pharmaceuticals (UK)

Jeremy Carmichael
SVP Corporate Development
Head of Business Development
Astex Pharmaceuticals
436 Cambridge Science Park
Milton Road, Cambridge
CB4 0QA, UK

Tel: +44 1223 226289
Email: jeremy.carmichael@astx.com

Media Enquiries

Sue Charles
Charles Consultants

Tel: +44 7968 726585
Email: sue@charles-consultants.com

Astex and Cardiff University Medicines Discovery Institute Announce New Drug Discovery Collaboration on Neurodegenerative Diseases

Cambridge and Cardiff, UK, 13 February 2023, Astex Pharmaceuticals (UK) (“Astex”), a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system and The Medicines Discovery Institute, Cardiff University (“MDI”) announced today that they have entered into a multi-year, multimillion pound drug discovery research collaboration, aimed to identify new drugs to treat neurodegenerative diseases.

The collaboration brings together the world-leading research expertise of Dr Emyr Lloyd-Evans & Dr Helen Waller-Evans in lysosomal biology, the drug discovery capabilities of the MDI and the fragment-based drug discovery platform at Astex. The combined teams will focus on identifying compounds which modulate lysosomal activity as a way to develop potential new treatments for neurodegenerative diseases with high unmet medical need.  Lysosomes are a subset of organelles that are crucial for cellular function and mutations in the genes encoding lysosomal and associated proteins are linked to a number of neurodegenerative and lysosomal storage diseases for which there are currently no effective treatments.

Under the terms of the agreement, scientists at the MDI and Astex will collaborate to carry out drug discovery research against a chosen lysosomal target with the aim to identify and optimise compounds that modulate its activity.  Cardiff University will receive committed R&D funding and is eligible to receive development and regulatory payments if drug compounds progress and a royalty payment on the sales of any approved products.  Further financial details are not disclosed.

Prof Simon Ward, Director, Medicines Discovery Institute commented “We are excited to be working with Astex in a way that allows each partner to play to its individual strengths and build a combined team which is greater than the sum of its parts. This is a validation of the scientific and translational capabilities we have been building at Cardiff University over the last few years and we look forward to delivering outputs that may ultimately benefit patients for whom current treatment options are so limited. This is an excellent demonstration of the power of academic and industrial teams working together to try to solve currently intractable medical problems.”

Dr David Rees, FMedSci, FRSC, Chief Scientific Officer of Astex commented, “We are very excited about this opportunity to work with Cardiff University, Medicines Discovery Institute. Astex has a long tradition of effective collaborations between academia and industry which we believe is critical for the successful translation of basic science. This partnership aims to support and advance ground-breaking research with the potential to transform the lives of patients with neurodegenerative diseases.”

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. Astex is a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan.

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

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

About Cardiff University

Cardiff University is recognised in independent government assessments as one of Britain’s leading teaching and research universities and is a member of the Russell Group of the UK’s most research-intensive universities. The 2014 Research Excellence Framework ranked the University 5th in the UK for research excellence. Among its academic staff are two Nobel Laureates, including the winner of the 2007 Nobel Prize for Medicine, Professor Sir Martin Evans. Founded by Royal Charter in 1883, today the University combines impressive modern facilities and a dynamic approach to teaching and research. The University’s breadth of expertise encompasses: the College of Arts, Humanities and Social Sciences; the College of Biomedical and Life Sciences; and the College of Physical Sciences and Engineering, along with a longstanding commitment to lifelong learning. Cardiff’s flagship Research Institutes are offering radical new approaches to pressing global problems.

For more information about Cardiff University, please visit:  www.cardiff.ac.uk

About MDI

The Medicines Discovery Institute is the leading, university-based, CNS drug discovery group in Europe, delivering modern drug discoveries to improve treatments for neurological illnesses. Grounded in the academic & clinical excellence of Cardiff University, the team combines profound insight with industry-standard drug discovery. A robust pipeline of novel drug projects stretches from early drug screening through to human clinical trials, run at Cardiff. The Institute is led by Professors Simon Ward & John Atack.

For more information about Medicines Discovery Institute, please visit:  https://www.cardiff.ac.uk/medicines-discovery 

CONTACTS

At Medicines Discovery Institute

Richard Angell
Commercialisation Lead
Medicines Discovery Institute
Cardiff University
Main Building
Park Place
Cardiff
CF10 3AT
Email: angellr@cardiff.ac.uk

Media Enquiries

Heath Jeffries
Head of Innovation Communication
Cardiff University

Tel: +44 29 2087 70917
Email: jeffrieshv1@cardiff.ac.uk

At Astex Pharmaceuticals (UK)

Jeremy Carmichael
SVP Corporate Development
Head of Business Development
Astex Pharmaceuticals
436 Cambridge Science Park
Milton Road, Cambridge
CB4 0QA, UK

Tel: +44 1223 226289
Email: jeremy.carmichael@astx.com

Media Enquiries

Sue Charles
Charles Consultants

Tel: +44 7968 726585
Email: sue@charles-consultants.com