Indication-Specific Dosing and Dose-Evaluation Strategies in New Indications for Non-Oncology Monoclonal Antibodies.

Compared to traditional small molecule drugs, monoclonal antibodies (mAbs) often display more complex pharmacokinetic (PK) and pharmacodynamic (PD) properties that may be impacted by disease-specific factors. For mAbs in non-oncology indications, where the same drug might be used for conditions involving different organ systems and/or having different degrees of severity, the need for indication-specific dosing and/or tailored dose evaluation strategies is more evident. However, a comprehensive analysis on this topic has not been conducted for approved non-oncology therapies. In this work, we extracted literature information for non-oncology mAbs approved in the past 20 years to provide a comprehensive exploration of indication-specific dosing and dose evaluation strategies in the new indications. Our analysis included 21 mAbs with 50 supplemental approvals for new indications. Indication-specific dosing was prevalent, with 15 out of 21 mAbs having different recommended dosing regimens across two or more indications. The majority of the new indications were supported by Phase 2 dose-ranging studies and/or Phase 3 studies that evaluated more than one dosing regimen. Importantly, our analysis uncovered a relationship between indication-specific dosing, dose evaluation strategies, and organ system classification of the original versus the new indication. We delved into dose justification supporting the new indications, including the types of data and modeling approaches used or considered. Through case studies, we highlighted factors that may influence dose selection in new indications, such as target expression levels, disease severity, and benefit-risk profile. Lastly, we made practical recommendations regarding dose optimization approaches in clinical drug development across multiple indications.