BS01 Restores Light, Motion Detection in Retinitis Pigmentosa

Sheila Nirenberg, PhD

The AAV-mediate gene therapy BS01 showed promising vision improvements for 4 patients with retinitis pigmentosa (RP) who had complete or near-complete blindness, according to preliminary results from a phase 1/2 study shared by Bionic Sight, the developer of the therapy.

The first patient was treated in the study in March 2020, with 6-month results available for all 4 patients treated with low-dose (n = 2) and medium-dose BS01 (n = 2). All patients reported the ability to perceive light and motion, which was not possible prior to injection of the therapy. These changes were noted at 2 to 3 months following BS01 injection and confirmed at 3 and 6 months using unbiased visual stimuli testing. In 2 of the 4 cases (50%), patients could also detect the direction of motion.

The study is sequentially enrolling participants across doses, with an additional high-dose group now recruiting patients. Overall, the trial includes 3 dose escalation cohorts, with a fourth exploring a maximum tolerated dose in greater detail. The primary end point of the study is focused on adverse events.

“While the number of patients is still small, the consistency is very promising, with no safety concerns so far,” Sheila Nirenberg, PhD, founder of Bionic Sight and a professor at the Weill Medical College of Cornell University, said in a statement. “We’re looking forward to moving to the higher doses and plan to report additional results later this year.”

BS01 is a recombinant AAV-based gene therapy expressing an enhanced light-sensitive channelrhodopsin gene that is targeted to the optic nerve. The channelrhodopsin gene encodes light-sensitive, photoreceptor proteins which function to activate the optic nerve directly, bypassing the retina. The goal of the therapy is ultimately to restore vision through optogenetics.

Findings from the first 4 patients in the study provide proof of concept. "These results provide substantial evidence that BS01 is reaching the targeted cells and expressing the optogenetic protein at levels sufficient to produce visual responses, even at the lowest doses," the company said.

The phase 1/2 study plans to enroll 20 adult patients with RP, exclusively at OCLI Vision. Those having received prior AAV-based gene therapy are excluded from the trial, as are those with large amplitude nystagmus. Patients were required to have bare light perception in at least 1 eye. The secondary end points are focused on changes in light, shape, and motion detection by Diagnosys visual function testing.

Overall, those receiving low-dose BS01 experienced a 20-fold increase in light sensitivity compared with baseline levels. In the medium-dose arm, which delivered a treatment that contained 3 times more vector than the low-dose group, there was a 100-fold increase in light sensitivity, according to the company. The high-dose cohort began enrolling in early March. Additional findings from the study will be announced later this year.

“These early observations reported by Bionic Sight are very encouraging,” Todd Durham, PhD, vice president of Clinical and Outcomes Research at the Foundation Fighting Blindness, said in a statement. “Bionic Sight’s innovative approach has the potential to make a substantial difference to the lives of patients with RP and other retinal degenerative diseases.”