Retinitis Pigmentosa Research Advances

FDA Approves Spark’s Vision-Restoring Gene Therapy

Spark Therapeutics’ vision-restoring RPE65 gene therapy has received marketing approval from the U.S. Food and Drug Administration, becoming the first gene therapy to gain regulatory approval in the U.S. for the eye or any inherited condition. Known as LUXTURNA™ (voretigene neparvovec), the gene therapy restored vision in a clinical trial for people between the ages of 4 and 44 with Leber congenital amaurosis (LCA) caused by mutations in the gene RPE65. Study participants with severe vision loss reported putting away their navigational canes, seeing stars, being able to read, and recognizing faces of loved ones. Vision restoration has persisted for at least three years. The treatment is also designed to work for people with retinitis pigmentosa (RP) caused by RPE65 mutations. FFB invested about $10 million in more than a decade of lab research that made possible the RPE65 gene therapy clinical trial at the Children’s Hospital of Philadelphia (CHOP).

Three Companies Are Conducting Clinical Trials for Their Optogenetic Therapies for Advanced RP

GenSight, Bionic Sight, and Nanoscope have each launched clinical trials for their optogenetic therapies for RP and potentially other retinal diseases. The treatments are designed to provide vision to people who are completely blind from conditions such as retinitis pigmentosa and Usher syndrome. GenSight and Bionic Sight are designed to work by bestowing light sensitivity to ganglion cells in patients who have lost all of their photoreceptors. Nanoscope is targeting bipolar cells. All three companies have reported some modest restored vision in their early stage trials.

AGTC, Janssen/MeiraGTx, and 4DMT Conducting XLRP Gene Therapy Clinical Trials

Three companies are each conducting XLRP (RPGR) gene therapy clinical trials. MeiraGTx is in Phase 3 and AGTC is planning its Phase 3 trial. Both companies have reported vision improvements (retinal sensitivity and/or visual acuity) for patients in their Phase 1/2 trials. 4DMT is conducting a Phase 1/2 XLRP gene therapy clinical trial.

Coave Conducting Gene Therapy Clinical Trial for RP (PDE6B Mutations)

The French biotech Coave is conducting a Phase 1/2 gene therapy clinical trial for people with retinitis pigmentosa (RP) caused by PDE6B mutations. The three-year trials taking place at University Hospital of Nantes in France will enroll a total of 12 patients.

Nacuity Conducting Clinical Trial for Oral Antioxidant Therapy

Dallas-based Nacuity is conducting a Phase 1/2 clinical trial in Australia for its oral antioxidant therapy. The trial is for people with Usher syndrome (retinitis pigmentosa with hearing loss). The Foundation Fighting Blindness is investing up to $7.5 million to advance the promising, emerging drug for retinitis pigmentosa, Usher syndrome, and related conditions. Known as N-acetylcysteine-amide (NACA), the molecule is designed to slow vision loss by protecting retinal cells from oxidative stress. In previous Foundation-funded lab studies at Johns Hopkins University, NACA slowed retinal degeneration in rodent models of RP.

SparingVision Plans Clinical Trial to Evaluate Sight-Saving Protein for RP

A spin-off of the Institut de la Vision, SparingVision was established to clinically develop and commercialize a protein known as rod-derived cone-viability factor (RdCVF). The emerging therapy performed well in several previous lab studies funded by the Foundation Fighting Blindness. Scientists demonstrated that RdCVF prevented or slowed the degeneration of cones, the cells in the retina that provide central and color vision and enable people to read, drive, and recognize faces. RdCVF is naturally secreted by rods, the retinal cells that provide night and peripheral vision. The company has received FDA authorization to launch a Phase 1/2 clinical trial for the emerging therapy at the University of Pittsburgh Medical Center.

Ocugen Launches Phase 1/2 Clinical Trial for NR2E3 Gene Therapy

Ocugen, a developer of gene therapies targeting eye diseases as well as a vaccine for COVID-19, has received authorization from the US Food & Drug Administration to launch an 18-participant, Phase 1/2, NR2E3 gene therapy clinical trial for the following conditions:

• Retinitis pigmentosa caused by autosomal dominant mutations in NR2E3
• Retinitis pigmentosa caused by autosomal dominant mutations in rhodopsin (RHO)
• Retinitis pigmentosa, enhanced S-cone syndrome, and Goldmann-Favre syndrome caused by autosomal recessive mutations in NR2E3

Known as OCU400, the emerging gene therapy uses a human-engineered adeno-associated virus (AAV) to deliver copies of the NR2E3 gene to retinal cells. OCU400 is designed to potentially slow disease progress for many inherited retinal diseases, independent of the mutated gene causing the patients’ retinal condition. Additional information on trial sites and participant enrollment is forthcoming on clinicaltrials.gov.

JANUARY 2023