Gene Therapy for LCA10: The Brilliance Phase 1/2 Clinical Trial Of AGN-151587 (EDIT-101) Update

The Brilliance Phase 1/2 Clinical Trial Of AGN-151587 (EDIT-101) For The Treatment Of LCA10

This is an open-label, single ascending dose study of AGN-151587 (EDIT-101) in adult and pediatric (ie, ages 3 to 17) participants with LCA10-IVS26. Approximately 18 participants will be enrolled in up to 5 cohorts to evaluate up to 3 dose levels of AGN-151587 in this study. AGN-151587 is a novel gene editing product designed to eliminate the mutation on the CEP290 gene that results in the retinal degeneration that defines LCA10-IVS26.

Single-dose of AGN-151587 administered by subretinal injection surgery
Participants will receive a single dose of AGN-151587 administered via subretinal injection in the study eye. Up to 5 cohorts across 3 doses will be enrolled in this study.

Primary Outcome Measure
  • Frequency of Adverse Events related to AGN-151587 
  • Number of participants experiencing procedural related adverse events 
  • Incidence of dose limiting toxicities
Secondary Outcome Measures
  • Maximum tolerated dose as determined by the occurrence of dose-limiting toxicities
  • Change from baseline in Mobility course score 
  • Testing the subjects visual function by having the subject walk through obstacle courses. 
  • Change from baseline in LogMAR measurement of BCVA
  • Change from baseline in pupillary response
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Update March 2020

Dosing Of First Patient In Landmark Phase 1/2 Clinical Trial Of CRISPR Medicine AGN-151587 (EDIT-101) For The Treatment Of LCA10

Allergan plc (NYSE: AGN), a leading global pharmaceutical company, and Editas Medicine, Inc. (Nasdaq: EDIT), a leading genome editing company, today announced the treatment of the first patient in the BRILLIANCE clinical trial of AGN-151587 (EDIT-101) at Oregon Health & Science University (OHSU) Casey Eye Institute, a world-recognized academic eye center.

Therapeutic Approach: 

EDIT-101 (also known as AGN-151587) is tested for its ability to remove a point mutation in the CEP290 gene, which causes type 10 of the retinal degenerative disease Leber congenital amaurosis (LCA). The schematics are given below

Non-Clinical Evidence of Correction of CEP290 Mutation by CRISPR/Cas9 system

"Key to this therapeutic, we identified a pair of Staphylococcus aureus Cas9 guide RNAs that were highly active and specific to the human CEP290 target sequence. In vitro experiments in human cells and retinal explants demonstrated the molecular mechanism of action and nuclease specificity. Subretinal delivery of EDIT-101 in humanized CEP290 mice showed rapid and sustained CEP290 gene editing. A comparable surrogate non-human primate (NHP) vector also achieved productive editing of the NHP CEP290 gene at levels that met the target therapeutic threshold, and demonstrated the ability of CRISPR/Cas9 to edit somatic primate cells in vivo. "
Publication: Nature Medicine:25, pages229–233(2019)

Editas Medicine
Allergan plc