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Nonclinical Studies for Enzyme Replacement Therapies: FDA Finalizes Guidance

Posted 02 October 2019 | By Zachary Brennan 

Nonclinical Studies for Enzyme Replacement Therapies: FDA Finalizes Guidance

The US Food and Drug Administration (FDA) on Wednesday finalized guidance to help sponsors design and conduct nonclinical studies for developing investigational enzyme replacement therapy (ERT) products.

ERT products, which generally involve exogenously supplying the missing or defective protein, can treat an array of disorders resulting from inherited defective genes (e.g., Gaucher disease, Fabry disease, Pompe disease and mucopolysaccharidoses), FDA explains.

The nine-page guidance, which finalizes a draft released in May 2015, discusses various recommendations for designing the nonclinical program, including selecting animal species, animal models of disease, toxicology studies, good laboratory practice, and product development for later-phase clinical trials and marketing applications.

FDA also noted in Wednesday’s Federal Register notice that the final version includes revisions based on comments submitted in 2015 by Eisai, Merck, Shire and industry group BIO.

“Changes from the draft to the final include the following: ‘Changes in disease-specific biomarkers’ has been added as a pharmacodynamic endpoint; a statement on the preference for animal disease models in assessing pharmacodynamic activity has been added; safety pharmacology parameters to proof-of-concept studies were added; a statement was added to clarify the exposure margins; a clarification on the rapidly progressing disease phenotype was provided by adding ‘approximately’ 1 year; a statement on the 3-month toxicology study in one species to support marketing approval was added; and a statement on recovery animals was added,” FDA said.

The agency also noted that this is the only final guidance that provides recommendations about the substance and scope of nonclinical information needed to support initiation of clinical trials, ongoing clinical development and marketing approval of ERT products.

“This guidance provides consistent recommendations for nonclinical studies to expedite developments of ERT products used to treat these rare, life-threatening conditions, especially in pediatric patients,” FDA added.

Investigational Enzyme Replacement Therapy Products: Nonclinical Assessment


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