Optogenetic Gene Therapy Restores Vision in 11 Retinitis Pigmentosa Patients

Nanoscope Therapeutics Inc. today announced that vision improvements for all evaluated advanced retinitis pigmentosa (RP) patients persisted through one year following a single intravitreal injection in a Phase 1/2a clinical study with multi-characteristic opsin (MCO).

"We expect to begin the first randomized, placebo-controlled, double-masked Phase 2b multi-center optogenetic trial in the US this summer to further validate our gene therapy's ability to improve clinically meaningful vision in RP patients,” Nanoscope CEO Sulagna Bhattacharya said in a statement. “If successful, it will be the first-ever restorative drug for millions of RP patients worldwide.”

Three patients received low dose (1.75 × 1011 VG per eye) and eight received a high dose of 3.5 × 1011 VG per eye. Florescence imaging of retina revealed successful gene transduction. At completion, 6 out of 7 (86%) high dose MCO-therapy subjects gained >0.3 logMAR (15 letters). Due to COVID-19, one of the high dose subjects was not evaluated after 31 weeks of treatment.

According to Nanoscope CMO and ophthalmologist Sai Chavala, MD, the safety and efficacy results from the clinical study have demonstrated that the benefit-risk balance is strongly in favor of MCO for the treatment of vision loss due to RP.

“The patients have improved irrespective of underlying gene mutation(s) that caused the disease," Chavala said in a statement.

All subjects had objective and subjective improvement in functional vision. The shape discrimination accuracy improved to > 90% in all subjects compared to baseline. Further, the performance in two different mobility tests improved by 50% reduction in time to touch lighted panel. These test outcomes were highly correlated with improved patient reported outcomes.

Santosh Mahapatra, MD, an ophthalmologist, eye surgeon and principal investigator, noted that after MCO-treatment, the patients reported long-lasting improvements in outdoor light sensitivity and daily activities.

“We were pleasantly surprised that after eight weeks of treatment, some subjects could attend their follow-up visits during the study without the assistance of a chaperone,” Mahapatra said in a statement. “Some of the patients even gained the ability to read letters on a wall or even the large text in a newspaper, use a cell phone, watch television, and could even thread a needle."

Nanoscope's RP gene therapy, which has received orphan drug designation from the US Food and Drug Administration, uses a proprietary AAV2 vector to deliver the MCO genes into the retina. This mutation-independent gene therapy involves a single injection through the eye administered in a doctor's office.

Samarendra Mohanty, PhD, Nanoscope's president, chief scientific officer and inventor of the technology, said in a statement that "optogenetics is a powerful research tool, but had limited scope of clinical benefit because the opsins had a narrow band of activation, unlike natural light environment. MCO is sensitive to broadband light and activatable by ambient light, thus eliminating the risk of photo-toxicity from long-term continuous use of external intense light stimulation devices."