Sequential PK Study Designs May Further Accelerate IV-to-Subcutaneous Biologic Development

Dr. Charles Theuer spoke with BioPharm International during AAPS NPC 2026, highlighting emerging regulatory changes that may significantly simplify the transition from prefilled syringes to auto-injector presentations for biologic therapies. During his presentation —“Development Pathways and Considerations for Subcutaneous Biologic Formulations,”— he discussed increasingly streamlined approaches for converting intravenous (IV) biologics into subcutaneous formulations.

According to Theuer, developers typically begin the transition process with a Phase I study designed to identify a subcutaneous dose capable of achieving exposure levels comparable to the approved IV product. He explained that companies rely heavily on prior exposure-response analyses conducted during IV drug development, particularly pharmacokinetic (PK) parameters associated with efficacy such as C trough concentrations.

Could Sequential Treatment Designs Reduce Clinical Trial Burden for Subcutaneous Biologics?

Theuer highlighted growing interest in sequential treatment study designs, which use each patient as their own control rather than comparing separate IV and subcutaneous treatment cohorts. In these studies, patients first receive the approved IV therapy until steady-state exposure is achieved. After transitioning to the subcutaneous formulation and reestablishing steady state, investigators reassess PK parameters and compare the two exposure profiles directly within the same patient. “The pathway to convert from IV to sub q is actually very streamlined,” Theuer said.

The approach may substantially reduce variability commonly observed between independent patient cohorts, allowing sponsors to decrease sample sizes while still demonstrating non-inferiority across key PK endpoints. According to Theuer, some sequential treatment studies may require fewer than 100 patients.

He also emphasized that regulatory pathways for IV-to-subcutaneous conversions continue to evolve. Alongside streamlined PK-focused non-inferiority studies, initiatives such as the European Union’s Model Molecule Independent Device Bridging Approach (MIDBA) may further reduce development burdens associated with auto-injector approvals.

The trend reflects broader industry efforts to accelerate patient-centric biologic delivery strategies and simplify development pathways for subcutaneous biologics, drug-device combination products, and alternative biologic dosage forms.

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About the speaker

Charles Theuer, MD, PhD

Dr. Charles Theuer has served as Chief Medical Officer at Halozyme since October 2024, leading subcutaneous drug development initiatives involving ENHANZE® technology and auto-injectors. Previously, he was CEO, CMO, and Director of TRACON Pharmaceuticals and held senior leadership roles at TargeGen, Pfizer, and IDEC Pharmaceuticals, contributing to the development of therapies including Inrebic®, Sutent®, Rituxan®, and Zevalin®. A board-certified general surgeon for more than a decade, Theuer earned degrees from MIT, UCSF, and UC Irvine, and completed training at Harbor-UCLA Medical Center and the National Cancer Institute.