J&J gene therapy is used for rare, progressive visual disorder failure 3-stage test
Johnson & Johnson’s gene therapy is developing hereditary visual disorders, a Phase 3 study, the latest clinical research setback in rare eye diseases, which so far has no FDA-approved therapy.
Gene therapy, botaretrigene sparoparvovec (bota-vec for short), is being evaluated as a treatment for X-linked retinal pigment (XLRP). The results were “statistically not significant but supportive in orientation,” J&J reported Friday, based on the primary goal of vision changes in the year assessed by the patient’s ability to visually browse the maze.”
XLRP causes the photoreceptors of the photoreceptors of the photoreceptors of the retina. It is caused by mutations in the RPGR gene, which encodes vision protein bonds. Without this protein, gradually worsening vision loss often leads to legal blindness by the age of 40.
BOTA-VEC uses engineered viruses to pass stable gene sequences to rods and con photoreceptors in the eye. This one-time treatment is designed to enable these cells to express functional RPGR proteins to maintain vision. The third phase of the test recruited 95 patients who were randomly assigned to groups receiving low or high doses of experimental therapy, or to controls with delayed treatment (the intervention was not done until subsequent studies of gene therapy were performed on the cohort).
Although major clinical trial goals were not met, J&J reported improvements in secondary endpoints, including functional vision, retinal function and visual function. On the safety side, J&J said all participants in the pooled treatment group encountered at least one treatment-related adverse event, most of which were classified as mild or moderate. About 70% of participants developed eye inflammation. In the pooled treatment group, 29 participants developed cataract-related problems. In the deferred treatment group, six encountered such problems. No deaths were found in the study.
BOTA-VEC comes from a study of Meiragtx, a gene therapy biotechnology. In 2019, the biotech began working with J&J subsidiary Janssen's gene therapy for hereditary retinal diseases. J&J paid Meiragtx $100 million to start the league, which included the Bota-Vec program. The pharmaceutical giant paid $30 million in milestone payments, according to Meiragtx regulatory filings.
In 2023, J&J agreed to advance $130 million in upfront and near-term milestone payments to obtain the remaining rights of Bota-Vec. Meiragtx's earned milestone payments are associated with potential commercialization of gene therapy.
XLRP hinders other gene therapy research efforts. Biogen's nuclear leaf gene Toliparvovec did not meet the main goal of phase 2/3 testing in this ophthalmic disease in 2021. Based on the failure of the trial, Biogen subsequently stopped further developments of the program, which came from its 2019 acquisition of Nightstar Therapeutics.
Other research is still underway for XLRP. Beacon Therapeutics is currently undergoing phase 2/3 testing of the disease with Laru-Zova. The biotechnology says its gene therapy is unique by expressing the full length of the RPGR protein. In December last year, Beacon reported results for the temporary phase 2, showing that LARU-Zova leads to increased vision expected in low-light conditions. At this temporary reading, the therapy was reported to be safe and well tolerated. The Beacon Phase 2/3 study continued to recruit participants.
Photo: Mario Tama, Getty Images
