Regenxbio plans to provide updates on its gene therapy candidates RGX-181 and RGX-381 for late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), one of the most common forms of Batten disease, in the second half of this year.
The company is currently reviewing requests for information from the U.S. Food and Drug Administration (FDA), regarding a clinical hold the agency placed on a proposed trial of RGX-181, after the company submitted a request investigational new drug (IND).
In an open letter to the Batten disease community, Regenxbio said the FDA has requested more information regarding “initial dose selection and certain study drug administration procedures.”
The delay involved in responding to the FDA’s request also pushed updates to the RGX-381 program into the second half. Regenxbio intended to submit an IND application for RGX-381 to the FDA or foreign drug regulatory authorities this year.
RGX-181 is a single-use investigational gene therapy designed to provide a functional copy of the TPP1 gene to cells of the central nervous system (CNS, brain and spinal cord).
Mutations in TPP1 causes CLN2. The enzyme produced by this gene is essential for breaking down fat and protein molecules called lipofuscins, which then accumulate in toxic amounts, eventually killing the cells in which they are found. Nerve cells are particularly susceptible to damage from lipofuscins, resulting in the neurological symptoms seen in CLN2.
Preclinical data from studies involving animal models of CLN2 showed that a single injection of RGX-181 significantly improved neurological symptoms and survival times in animals by increasing the amount of TPP1 enzyme throughout the CNS.
The FDA has granted the experimental therapy rare pediatric disease and orphan disease designations, both intended to help bring a potential drug to market.
RGX-381 is intended to provide the TPP1 directly on the retina – the layer of the eye containing light-sensitive cells – to correct symptoms of CLN2 in the eyes (eye manifestations). The ocular manifestations generally appear around the age of 4 years. They involve rapid vision loss, progressing to blindness over several years. No treatment currently exists for CLN2-related vision loss.
Both therapies use an adeno-associated virus to deliver their copies of TPP1. These non-replicating viruses are a common gene therapy tool, used because they cannot cause disease and rarely trigger immune responses.