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EpiVax and FDA's Significant Study on Teriparatide Impurities

EpiVax, Inc., in collaboration with the U.S. Food and Drug Administration (FDA) and scientists from CUBRC, Inc. based in Buffalo, NY, has published a groundbreaking study that dives into the immunogenicity risks associated with peptide-related impurities found in generic teriparatide products. The research focuses on the critical assessment of how these impurities could possibly trigger unwanted immune responses, raising notable concerns regarding the safety and efficacy of generic peptide drugs.

Teriparatide, a recombinant peptide designated for osteoporosis treatment, has been underscored in recent FDA guidance that suggests assessing immunogenicity risks for synthetic generics submitted via Abbreviated New Drug Applications (ANDAs). While maintaining active pharmaceutical ingredient sameness is a crucial requirement for regulatory approvals, the investigation acknowledges that impurities from the manufacturing process may cause sequence alterations that could introduce novel T-cell epitopes, possibly compromising the drug’s safety.

To systematically evaluate these risks, the study utilized EpiVax's renowned PANDA approach, which incorporates various assessment tools. This included in silico assessments that leverage T-cell epitope prediction and characterization through the company's innovative software, EpiMatrix® and JanusMatrix®, alongside in vitro human leukocyte antigen (HLA) binding assays and human T-cell assays.

Through advanced computational evaluations, the study identified multiple impurities exhibiting a higher predicted immunogenic potential when compared to the original teriparatide sequence. Experimental findings backed these predictions, as several impurities demonstrated enhanced HLA binding and a stronger T-cell response in laboratory analyses. Intriguingly, the researchers discovered a potentially tolerogenic region within the teriparatide sequence that might mitigate responses to the drug; however, this could be disrupted by impurities introducing sequence changes.

Dr. Vibha Jawa, Chief Scientific Officer of EpiVax, emphasized the significance of this collaboration with the FDA, illustrating the synergy between robust computational methods and wet-lab techniques. “This partnership showcases the power of our combined efforts in thoroughly understanding and alleviating immunogenicity risks present in generic peptide development,” Dr. Jawa explained. “Our research offers a practical framework to aid developers in navigating FDA guidance on impurity assessment while presenting opportunities to enhance peptide drug safety.”

The implications of this study are considerable for manufacturers producing generic peptides. By identifying specific impurities that could escalate immunogenic responses, the research guides these companies in controlling potentially harmful impurities within their drugs, a necessary step towards ensuring patient safety.

This research was executed with support from the FDA under contract number HHSF223018186C. While the findings are rooted in robust scientific inquiry, the authors noted that the content reflects their own views and does not necessarily represent the official positions of the FDA or the U.S. Government. The collaboration between the scientific community and regulatory agencies demonstrates a crucial step forward in addressing safety concerns related to generic peptides, paving the way for improved therapeutic outcomes for patients reliant on these essential medications.