FDA Provides Recommendations for Antibody Drug Conjugate Development

The US Food and Drug Administration (FDA) has issued draft guidance on clinical pharmacology considerations for potential manufacturers of antibody drug conjugates (ADCs). According to the agency, there is no existing guidance addressing these drugs, which are regulated as biologic drug combination products.

This new guidance addresses bioanalytical methods, dosing strategies, dose and exposure response analyses, QTc assessments, immunogenicity, and drug-drug interactions.

“[ADCs] combine the selectivity of antibody for a specific target with the potency of a small-molecule drug,” FDA officials explained. “Therefore, development of ADCs requires careful consideration of the differences between the clinical pharmacology of the antibody or antibody fragment and the small molecule.”

To date, the FDA has approved 12 ADCs, including:

• ado-trastuzumab emtansine for metastatic breast cancer
• polatuzumab vedotin for relapsed or refractory diffuse large B-cell lymphoma
• brentuximab vedotin for relapsed or refractory Hodgkin lymphoma
• tisotumumab vedotin-tftv for metastatic cervical cancer

Source: RAPS.org, Feb. 8, 2022; FDA draft guidance.