Gyroscope posts early win with gene therapy for AMD, giving hope for its immune complement system target
Gene therapies for blindness are nothing new after Roche’s Spark unit hooked an FDA approval for Luxturna back in 2017. But a UK biotech hoping to turn its gene therapy against an overactive immune complement system tied to vision loss is now sporting data that could help change the game in AMD.
In a Phase I/II dose escalation trial, patients who responded to Gyroscope’s gene therapy GT005 saw a 146% increase in their vitreous Complement Factor I levels as well as a decrease in downstream biomarkers tied to geographic atrophy for patients with dry AMD, according to data unveiled Friday at the virtual Angiogenesis, Exudation, and Degeneration meeting.
At an interim check-in, nine out of 10 patients across four cohort groups saw increased CFI levels after receiving the therapy, and eight of those nine maintained elevated levels of CFI after six months. The earliest patient dosed in the open-label study was still showing elevated levels at 84 weeks, Gyroscope said.
Gyroscope believes raising CFI levels can dampen an overactive immune complement system, which has been connected to worsening atrophy in AMD patients, according to a release.
GT005 also spurred lower levels of proteins associated with an overactive complement system. Patients saw an average decrease of 41% in Ba protein levels compared to baseline between weeks 24 and 56, and an average decrease of 42% C3 breakdown protein levels compared to baseline during the same period.
According to Nadia Waheed, Gyroscope’s CMO, seeing big cuts in biomarkers tied to the complement system could help support the mechanism of action behind GT005 and add weight to a pivotal trial down the road.
“Consistently we’re hitting the targets we want to hit in the downstream amplification loop,” she said. “Everything so far looks like it’s pointing in the right direction.”
The therapy’s safety profile was mostly clean, although Gyroscope did report one potentially treatment-related side effect — a case of choroidal neovascularization, a major cause of vision loss. Waheed said an early investigation indicated the event was probably not related to the therapy and was more likely a result of the patient’s worsening condition. Choroidal neovascularizations are common in patients treated with anti-VEGF therapies, Waheed said, due in part to the structure of the molecule used in treatment.
“We don’t think we should see an increase (in those events over time), but of course we follow it very closely,” she said.
In terms of next steps, Waheed said the Phase I/II FOCUS trial would finish enrollment by the end of 2021. Meanwhile, the company is also enrolling two Phase II efficacy trials for GT005 and Waheed said her team is “on track” to get those filled out.