Biogen’s inherited eye disease gene therapy misses primary endpoint

A gene therapy developed by Biogen for the rare inherited eye disease X-linked retinitis pigmentosa (XLRP) has failed to meet the primary endpoint in a Phase II/III study.

The XIRIUS study was conducted in two parts – a Phase I portion enrolling 18 patients which aimed to establish the dosing regimen, and a Phase II/III portion that enrolled an additional 23 participants aged over ten years old.

The Phase II/III portion separated patients into three groups, in a bid to compare the low dose and high dose of cotoretigene toliparvovec to an untreated group to enable a controlled comparison of efficacy and safety.

The study aimed to measure changes in retinal sensitivity at one year using a macular integrity test, with the goal of evaluating if the gene therapy could induce improvements from baseline across different locations on the retina.

However, Biogen’s therapy ultimately showed no significant improvement over the control group on this measure – the primary endpoint – although the company added that ‘positive trends’ were seen across a number of prespecified secondary endpoints.

“Although the Phase II/III 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,  head of the therapeutics development unit at Biogen.

XLRP is associated with progressive vision loss, as the condition causes the light-sensing cells of the retina to gradually deteriorate. Currently, there are no approved treatments for people living with XLRP.

“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 programme,” added Dawson.