Pharmacokinetic/Phamacodynamic (PK/PD) Modeling Providing Guidance for Selecting Avatrombopag (AVA) Dose When Switching from Eltrombopag in Chronic Immune Thrombocytopenia (ITP)

Vredenburg, Michael

Oral and Poster Abstracts
311. Disorders of Platelet Number or Function: Poster I

Bleeding Disorders, Diseases, Bleeding and Clotting, ITP, Platelet Disorders, Thrombocytopenias

Nashat Y. Gabrail, MD¹^*, Kavita Aggarwal, PharmD²^*, Michael Vredenburg, PhD²^*, Ruemu Birhiray, MD³ and Brian Jamieson, MD, BA²

¹Gabrail Cancer Center, Canton, OH
²Dova Pharmaceuticals, Durham, NC
³Hematology Oncology of Indiana, PC/American Oncology Network, PA, Indianapolis, IN

Introduction: Clinical management of ITP patients can be complex. Changing therapy is based on a variety of factors including efficacy, safety and compliance. AVA is approved for chronic ITP patients with insufficient response to previous treatments. AVA, taken with food, may be viewed as a viable switch option for patients who respond to eltrombopag (ELT) yet struggle with the requisite food restrictions. However, no dose switching guidance exists.
Aim: PK/PD simulations were conducted to inform clinicians on how to initiate a switch from ELT to AVA.
Methods: Population PK and PK/PD models were developed for AVA from 12 studies in healthy subjects and 4 studies in ITP patients. Similar models were previously conducted to simulate ELT concentration-time and platelet-time profiles (Gibiansky 2011, Hayes 2011).
The simulations used fixed daily dosing and included only responders to ELT. Switch simulations included daily dosing with ELT of 25 mg, 50 mg, or 75 mg with a switch to various AVA doses including 20 mg dosing once daily (QD) and three times a week (TIW); AVA dosing started 24 hours after the last ELT dose. These simulations identified regimens for AVA after switching from ELT to maximize platelet counts in the target range (50 to 200×109/L) and minimize those with decreases below 30×109/L.
Results: For the ELT to AVA switch, the simulations included 92 non-Asian ITP patients, which were replicated 100 times. Platelet-time profiles suggested AVA was more potent than ELT for a given dose amount per day. The data support initiating AVA 24h post the last ELT dose. Modeled platelet response data will be presented at the meeting. Based on the model, Table 1 shows the recommended switching dose.
Conclusions: This modeling data provides useful dosing guidelines for AVA to maintain platelet counts in the target range for ITP patients when switching from ELT to AVA.

Disclosures: Gabrail: Dova Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Aggarwal: Dova Pharmaceuticals: Ended employment in the past 24 months. Vredenburg: Dova Pharmaceuticals: Current Employment. Birhiray: Novartis: Consultancy, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lilly: Speakers Bureau; Genomic Health: Speakers Bureau; Jansen Bioncology: Consultancy, Speakers Bureau; Puma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Speakers Bureau; Incyte: Speakers Bureau; Rigel Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Speakers Bureau; Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi Oncology: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Speakers Bureau; Exelexis: Speakers Bureau; Pharmacyclics: Speakers Bureau; Glaxo: Speakers Bureau; Morphosys: Speakers Bureau; BMS: Speakers Bureau; Pfizer: Speakers Bureau; Daiichi Sankyo: Speakers Bureau. Jamieson: Dova Pharmaceuticals: Current Employment.

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^*signifies non-member of ASH

848 Pharmacokinetic/Phamacodynamic (PK/PD) Modeling Providing Guidance for Selecting Avatrombopag (AVA) Dose When Switching from Eltrombopag in Chronic Immune Thrombocytopenia (ITP)