ARVO 2019: Gene Therapy Clinical Trial for RP Caused by RLBP1 Mutations Ongoing in Sweden

Novartis, a global developer of pharmaceuticals and biologic medicines, is conducting a Phase 1/2 gene therapy clinical trial in Sweden for people with retinitis pigmentosa (RP) caused by mutations in the gene RLBP1. The study will evaluate as many as 21 participants. Five dose levels will be evaluated.

The RLBP1 gene encodes a protein that plays a critical role in making the retina light sensitive. RP caused by mutations in RLBP1 leads to slow dark adaptation for young people and severe vision loss for those who are middle-aged or older.

In a Novartis lab study, mice with RLBP1 mutations had improved dark adaptation after receiving the gene therapy. The treatment remained effective after one year.

The treatment involves the subretinal injection of healthy copies of the RLBP1 gene to augment the patient’s mutated copies. The RLBP1 gene copies are contained in a human-engineered adeno-associated virus (AAV), which is designed to penetrate retinal cells to deliver the therapeutic copies.

“We are pleased to move a gene therapy for people with retinitis pigmentosa caused by RLBP1 mutations into a human study. The condition leads to significant vision loss, and we are encouraged by the potential for gene therapy to save, or possibly restore, their vision ,” said Kali Stasi, MD, PhD, a translational medicine expert in ophthalmology at Novartis who leads the program and helped design the study. She spoke about the trial at the 2019 meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Vancouver, British Columbia, in Canada, April 28 – May 2.

A five-year natural history study for 45 people with RLBP1 mutations is about to be completed in Sweden and Newfoundland, Canada. The goal of the study is to better understand disease progression and identify additional clinical trial outcome measures to determine objectively if the gene therapy is working to save or restore vision.