Safety and Proof-of-Concept Study of Oral QLT091001 in Retinitis Pigmentosa Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT)

PLoS One. 2015 Dec 10;10(12):e0143846. doi: 10.1371/journal.pone.0143846. eCollection 2015.


Restoring vision in inherited retinal degenerations remains an unmet medical need. In mice exhibiting a genetically engineered block of the visual cycle, vision was recently successfully restored by oral administration of 9-cis-retinyl acetate (QLT091001). Safety and visual outcomes of a once-daily oral dose of 40 mg/m2/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18 patients with RPE65- or LRAT-related retinitis pigmentosa. Eight of 18 patients (44%) showed a ≥20% increase and 4 of 18 (22%) showed a ≥40% increase in functional retinal area determined from Goldmann visual fields; 12 (67%) and 5 (28%) of 18 patients showed a ≥5 and ≥10 ETDRS letter score increase of visual acuity, respectively, in one or both eyes at two or more visits within 2 months of treatment. In two patients who underwent fMRI, a significant positive response was measured to stimuli of medium contrast, moving, pattern targets in both left and right hemispheres of the occipital cortex. There were no serious adverse events. Treatment-related adverse events were transient and the most common included headache, photophobia, nausea, vomiting, and minor biochemical abnormalities. Measuring the outer segment length of the photoreceptor layer with high-definition optical coherence tomography was highly predictive of treatment responses with responders having a significantly larger baseline outer segment thickness (11.7 ± 4.8 μm, mean ± 95% CI) than non-responders (3.5 ± 1.2 μm). This structure-function relationship suggests that treatment with QLT091001 is more likely to be efficacious if there is sufficient photoreceptor integrity.

Trial registration: NCT01014052.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics*
  • Acyltransferases / metabolism
  • Administration, Oral
  • Adult
  • Anticarcinogenic Agents / adverse effects
  • Anticarcinogenic Agents / pharmacology
  • Anticarcinogenic Agents / therapeutic use*
  • Cerebral Cortex / diagnostic imaging
  • Child
  • Diterpenes
  • Drug Dosage Calculations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Radiography
  • Retinal Ganglion Cells / pathology
  • Retinal Neurons / pathology
  • Retinitis Pigmentosa / drug therapy*
  • Retinyl Esters
  • Treatment Outcome
  • Visual Acuity / drug effects
  • Visual Fields / drug effects
  • Vitamin A / adverse effects
  • Vitamin A / analogs & derivatives*
  • Vitamin A / pharmacology
  • Vitamin A / therapeutic use
  • Young Adult
  • cis-trans-Isomerases / genetics*
  • cis-trans-Isomerases / metabolism


  • Anticarcinogenic Agents
  • Diterpenes
  • Retinyl Esters
  • Vitamin A
  • retinol acetate
  • Acyltransferases
  • lecithin-retinol acyltransferase
  • retinoid isomerohydrolase
  • cis-trans-Isomerases

Associated data