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PBSS – INQOVI by Astex – Otsuka for the treatment of myelodysplastic syndromes (MDS)

December 15, 2022 @ 11:30 am - 2:00 pm

Decitabine is a hypomethylating agent (HMA) and was approved by FDA for treatment of intermediate/high-risk MDS for IV infusion in 2006. Oral administration of decitabine, or other HMAs as single agent, has proven challenging as high first-pass due to metabolic degradation by cytidine deaminase (CDA) results in low bioavailability. Cedazuridine, a synthetic analog of tetradrouridine, is a potent inhibitor of CDA and oral combination with decitabine enhances its bioavailability. Astex developed INQOVI, oral decitabine+cedazuridine, and achieved approval of the label with the same indication as IV decitabine, using clinical pharmacology data as primary endpoint in the registrational phase-3, targeting pharmacokinetic (AUC) equivalence against reference IV decitabine to demonstrate biological comparability. Additional supportive pharmacodynamic data (LINE-1 demethylation) were also submitted. Clinical efficacy and safety were secondary endpoints in phase-3. Details of clinical development (including nonclinical background); regulatory considerations; clinical pharmacology endpoints comparing oral vs IV; CMC challenges and evolution and development of formulation for the combination, including the final fixed-dose combination single tablets will be presented.


Seminar Outline:

General presentation (~45 min):

  • Introduction on INQOVI (oral decitabine + cedazuridine)
  • Program progress through development (nonclinical to clinical to registration) and registration strategy
  • Topline data used for submission
    • PK, PD (primary)
    • Clinical safety + efficacy (secondary)


CMC presentation (~45 min)

  • Development of DP
  • Challenges with early formulation(s) and  Capsules to tablet switch
  • Development of the FDC form and commercial form


Additional Clinical Pharmacology considerations (~20 min)

  • PopPK and Exposure-response
  • Oral vs IV comparisons

About the Speakers

  • Aram Oganesian, PhD, DABT, Vice President, Clinical Pharmacology & NonClinical Development, Astex Pharmaceuticals
  • Nipun Davar, PhD, MBAChief Corporate Officer & head of CMCAstex Pharmaceuticals



December 15, 2022
11:30 am - 2:00 pm
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