Biogen reports second gene therapy flop in rare retinal disease trial

Biogen reported Monday that its experimental gene therapy timrepigene emparvovec, acquired through its $800-million takeover of Nightstar Therapeutics in 2019, did not meet the primary or key secondary endpoints in the Phase III STAR trial of patients with choroideraemia. The news follows the recent study failure of cotoretigene toliparvovec, another gene therapy acquired via the Nightstar purchase, in X-linked retinitis pigmentosa (for related analysis, see ViewPoints: Biogen's gene therapy head start starts heading south).

The STAR trial enrolled 169 adult males with a genetically confirmed diagnosis of choroideraemia who were randomised to one of two doses of timrepigene emparvovec or an untreated control group. The study assessed how effective a single subretinal injection of the gene therapy would be at producing a ≥15-letter improvement from baseline in best-corrected visual acuity (BCVA), as measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart, at one year.

Weighing next steps

Besides missing the main goal, the STAR study also did not demonstrate efficacy on key secondary endpoints. Some secondary outcome measures being evaluated in the trial were the percentage of patients achieving a ≥10-letter improvement in BCVA at 12 months, and those with no decrease from baseline in BCVA. Biogen noted that safety results from the STAR trial were "consistent" with previous studies.

Detailed findings will be made available at a future scientific forum. Meanwhile, the company said it would analyse the complete dataset before deciding what its next steps are for the timrepigene emparvovec development programme. Biogen noted that the recombinant AAV2 vector, also known as BIIB111 or NSR-REP1, is designed to deliver a functional version of the human choroideraemia gene into the retinal pigment epithelium and photoreceptor cells so as to address the underlying genetic cause of this rare inherited retinal disease.

Earlier this year, Biogen signed an agreement to develop gene therapy products for inherited eye diseases using ViGeneron's novel vgAAV capsids to transduce retinal cells via intravitreal injections. It also recently announced a partnership with Capsigen to engineer optimised AAV capsids.

To read more Top Story articles, click here.