World Ophthalmology Congress

Cape Town, SA

June 26-29, 2020

Safety and Efficacy of Zuretinol Acetate in IRD
Caused by Mutations in RPE65 or  LRAT Mutations

Barrett Katz, MD, MBA, Glenn Noronha, PhD

BridgeBio Pharmaceuticals and Retinagenix Therapeutics, Inc.

Palo Alto, CA, USA


To evaluate the safety and efficacy, and pharmacokinetics of Zuretinol Acetate (ZA) in subjects with biallelic recessive RPE65 or LRAT gene mutations diagnosed as Leber’s Congenital Amaurosis (LCA) or Retinitis Pigmentosa (RP).

RG201 is a world-wide Phase 2 clinical trial conducted at approximately 20 centers in the United States, Europe, Canada, India and Mexico. It is a three-armed study with a single low dose, a single high dose and a placebo control arm of ZA administered orally. Primary efficacy endpoint is FUNCTIONAL VISION as ascertained on a visual navigation course tested using multiple luminance levels. Secondary endpoints include area and volume of visual field, SD-OCT, and patient reported outcomes. Results will be summarized for each cohort arm using descriptive statistics with comparisons of each active arm to the control arm.


Experience gained in selecting appropriate sites, implementing cross-border genetic testing, finding patients with an ultra-orphan disease and recruiting and retaining them, and the complexity of international efforts in coordinating and orchestrating a complex ophthalmologic study such as this will be shared.

Advances in molecular biology have raised awareness of identifying those ophthalmic diseases that are genetically driven. Avenues of drug development for such entities are now available to physicians and patients, and active discovery aggressively pursued. While gene therapy for RPE65 via viral vector sub-retinal injection has been demonstrated, such intervention is not widely available and its long-term success conjectural because it is only the area of retina immediately above the induced bleb that is treated. No therapies whatsoever are available for patients with LRAT mutations.  Pressing medical need persists for a more accessible and acceptable route of administration for these genotypes. ZA offers the potential for more practical administration, the ability to treat both eyes concurrently, and treat the entirety of each retina. The success of such efforts requires a global effort of committed cooperation as is illustrated by RG201.