Speakers: Aram Oganesian, PhD, DABT, and Nipun Davar, PhD, MBA (Astex Pharmaceuticals)
Organizers: Shichang Miao (Amgen), Cyrus Khojasteh (Genentech)
Date: 2022-12-15
Time: 11:30-13:00 Pacific Time
Registration fee: 0
Location: Online via Zoom
Major Sponsor:
Vendor show vendors registered to date:
Registration: http://www.PBSS.org
Registration deadline:2022-12-13  (it will close sooner if the seating cap is reached)

About the Topic

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

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

[Note: this event is part of the "Success Stories and Lessons Learned from Recent FDA Approvals", a joint series by PBSS and California Life Sciences (CLS). The Zoom link will be provided to the registrants 1+ days before the event]