Antibody-drug conjugates: from efficacy testing to bioassay evaluation in modern drug development

Area of Science:

• Oncology
• Biotechnology
• Drug Development

Background:

• Antibody-drug conjugates (ADCs) represent a rapidly expanding therapeutic class in oncology, with numerous drugs approved and in development.
• The multicomponent nature of ADCs necessitates specific considerations for their development and evaluation.

Purpose of the Study:

• To highlight the importance of a multicomponent approach in designing preclinical programs for ADCs.
• To emphasize the need for early identification of predictive biomarkers for ADC efficacy, specificity, and safety.
• To stress the requirement for developing mechanism-of-action-reflective bioassays for GMP lot release testing of ADCs.

Main Methods:

• Review of current ADC development and regulatory landscape.
• Analysis of challenges in preclinical ADC program design.
• Discussion of biomarker strategies for ADC assessment.
• Consideration of bioassay development for ADC manufacturing.

Main Results:

• 15 ADCs are FDA-approved, with over 250 in development, indicating significant growth.
• Preclinical programs and biomarker identification are crucial for assessing ADC efficacy, specificity, and safety.
• Bioassays must account for the multicomponent nature of ADCs for effective lot release testing.

Conclusions:

• Effective ADC development requires a holistic strategy addressing preclinical design, biomarker discovery, and manufacturing controls.
• The unique characteristics of ADCs demand specialized approaches to ensure therapeutic success and patient safety.
• Robust bioassays are essential for quality control in the GMP manufacturing of ADCs.