Phase 2/3 Gene Therapy Study for XLRP Does Not Meet Primary Endpoint, Shows Positive Trends in Secondary Endpoints

Topline results from the phase 2/3 XIRIUS study of cotoretigene toliparvovec (BIIB112), a gene therapy being investigated as a one-time therapy for patients with X-linked retinitis pigmentosa (XLRP), found that the study did not meet its primary endpoint of demonstrating a statistically significant improvement in the proportion of treated study eyes. However, positive trends in several prespecified secondary endpoints, such as a clinically relevant measure of visual acuity, were indicated by the data, according to the study authors.

XLRP is a rare, inherited retinal disease that is associated with progressive vision loss as the light-sensing cells of the retina gradually deteriorate. Initial symptoms are difficulty seeing at night, followed by restriction of the field of vision and eventually blindness in most people by 40 years of age. There are currently no approved treatments for XLRP.

“Although the phase 2/3 XIRIUS study of cotoretigene toliparvovec did not meet its primary endpoint, we are encouraged by positive trends in other pre-specified clinically relevant endpoints, such as a measure of visual acuity under low light conditions,” said Katherine Dawson, MD, in a press release. “XLRP is a serious, early-onset form of retinitis pigmentosa, and people living with it face almost certain blindness by the end of the fourth decade, commonly leading to loss of independence, depression and unemployment. We are working to further evaluate the data from the XIRIUS study before communicating potential next steps for the cotoretigene toliparvovec clinical development program.”

XIRIUS was a first-in-human, multicenter, randomized, three-arm dose-escalation and dose-expansion study of a single subretinal injection of cotoretigene toliparvovec in males with a genetically confirmed diagnosis of X-linked retinitis pigmentosa. An assessment at 12 months found that compared to the study eye of patients randomized to the untreated control group, there was a ≥7 dB improvement from baseline at ≥5 of the 16 central loci of the 10-2 grid assessed by Macular Integrity Assessment (MAIA) microperimetry. Complete analysis of the XIRIUS study is ongoing.

Most adverse events experienced by study participants were mild to moderate in severity, ocular in nature, and resolved. Biogen will communicate next steps for the program after analyzing the complete data set.


Biogen Announces Topline Results From Phase 2/3 Gene Therapy Study for XLRP [news release]. Biogen; May 14, 2021. Accessed May 19, 2021.