Frank Vinluan , 2025-05-05 21:01:00
A Johnson & Johnson gene therapy in development for an inherited vision-loss disorder has failed a Phase 3 study, the latest clinical research setback for a rare eye disease that so far has no FDA-approved therapies.
The gene therapy, botaretigene sparoparvovec (bota-vec for short), was being evaluated as a treatment for X-linked retinal pigmentosa (XLRP). On the main goal of showing change in vision at one year as assessed by a patient’s ability to visually navigate through a maze, the result was “not statistically significant but was directionally supportive,” J&J reported Friday.
XLRP leads to deterioration of photoreceptors, the light-sensing cells of the retina. It’s caused by mutations to the RPGR gene, which codes for a protein key to vision. Without that protein, progressively worsening vision loss typically results in patients becoming legally blind by the age of 40.
Bota-vec uses an engineered virus to deliver a stable gene sequence to the rod and con photoreceptors of the eye. This one-time treatment was intended to enable those cells to express functional RPGR protein to preserve vision. The Phase 3 test enrolled 95 patients randomly assigned to a group that received a low dose or high dose of the experimental therapy, or a control arm that deferred treatment (no intervention until the follow-up study, when this cohort was administered the gene therapy).
Despite falling short on the main clinical trial goal, J&J reported improvement on secondary endpoints, including functional vision, retinal function, and visual function. On safety, J&J said all participants in the pooled treatment group experienced at least one treatment-related adverse event, with the majority of those being classified as mild or moderate. Eye inflammation occurred in about 70% of participants. In the pooled treatment group, 29 participants developed problems related to cataracts; in the deferred treatment group, six experienced such problems. There were no deaths in the study.
Bota-vec came from the research of gene therapy biotech MeiraGtx. In 2019, that biotech began an inherited retinal disorders gene therapy collaboration with Janssen, a J&J subsidiary. J&J paid MeiraGtx $100 million up front to begin the alliance, which included the bota-vec program. In 2021, the pharma giant paid out a $30 million milestone payment, according to MeiraGtx regulatory filings.
In 2023, J&J agreed to pay $130 million in upfront and near-term milestone payments to acquire the remaining rights to bota-vec. MeiraGtx stood to earn up to $285 million more in milestone payments tied to potential commercialization of the gene therapy.
XLRP has stymied other gene therapy research efforts. Biogen’s cotoretigene toliparvovec did not meet the main goal of a Phase 2/3 test in this eye disease in 2021. Based on that trial failure, Biogen subsequently discontinued further development of the program, which came from its 2019 acquisition of Nightstar Therapeutics.
There’s still additional research underway in XLRP. Beacon Therapeutics is currently in Phase 2/3 testing in this disease with laru-zova. The biotech says its gene therapy stands apart from others by expressing the full length of RPGR protein. Last December, Beacon reported interim Phase 2 results showing laru-zova led to promising early improvements in visual acuity in low-light conditions. At the point of that interim readout, the therapy was reported to be safe and well tolerated. Beacon’s Phase2/3 study continues to enroll participants.
Photo: Mario Tama, Getty Images
