#USA #FDA #Providence #EpiVax #Teraparatide

New Findings on Generic Teriparatide from EpiVax and FDA

EpiVax, Inc., in partnership with the U.S. Food and Drug Administration (FDA) and CUBRC, Inc., has published compelling research shedding light on the immunogenicity risks associated with peptide-related impurities in generic teriparatide. The study, titled "Assessment of Immunogenicity Risk of Peptide-Related Impurities in Generic Teriparatide Products," explores how these impurities could potentially influence adverse immune responses to generic teriparatide (TPT), which is crucial for ensuring the safety and comparability of peptide-based generics.

Teriparatide, a recombinant peptide used to treat osteoporosis, is highlighted in a recent FDA guideline that recommends applicants systematically evaluate the immunogenicity risks of synthetic generics presented through an Abbreviated New Drug Application (ANDA). Establishing uniformity in the active pharmaceutical ingredient is crucial; however, impurities from manufacturing processes can alter sequences, leading to the potential creation of new T cell epitopes.

Using a multifaceted approach, the study systematically evaluates teriparatide alongside various theoretical or observed impurities. The methods utilized include EpiVax's PANDA in silico assessment (leveraging epitope prediction and characterization tools like EpiMatrix® and JanusMatrix®), in vitro HLA binding assays, and human T-cell assays. This robust methodology proved effective in identifying multiple impurities with an anticipated immunogenic potential exceeding that of the reference teriparatide sequence.

Experimental analyses supported these computational predictions, revealing enhanced HLA binding and T-cell responses for several impurities compared to teriparatide itself. Most notably, the research pinpointed a potentially tolerogenic region within the teriparatide sequence that could mitigate drug responses but be susceptible to alterations from impurity sequence changes.

Dr. Vibha Jawa, Chief Scientific Officer at EpiVax, stated, "This collaboration with FDA scientists emphasizes the power of combining rigorous computational methods and laboratory techniques to better understand and mitigate immunogenicity risks in generic peptide development. Our findings offer a practical framework for developers to adapt to the FDA's guidelines on impurity evaluations, highlighting opportunities to enhance peptide safety."

The insights from this study could greatly assist manufacturers of generic peptides in identifying concerning impurities that may compound immunogenicity, warranting stringent control measures in the generic medication.

FDA Funding Statement

The research described was conducted by EpiVax in collaboration with CUBRC, Inc. and FDA collaborators, supported by FDA contract HHSF223018186C. The content of this publication is solely the responsibility of its authors and does not necessarily represent the official views or endorsements by FDA/HHS or the United States Government.