Phase 2 INSIGHT study: Improved near vision with 2 drop formulations

LENZ Therapeutics has unveiled positive topline data from its INSIGHT study achieved by 2 formulations to treat presbyopia.

LENZ Therapeutics today reported positive topline results from its Phase 2 INSIGHT clinical trial of two investigational formulations of aceclidine to treat presbyopia.

According to the company, LNZ100 (aceclidine) and LNZ101 (aceclidine + brimonidine), achieved the primary and secondary endpoints.

The topline data results included the following:

• A 3-line or greater improvement was seen in the near visual acuity (VA), without a loss of 1 line (5 letters) of distance VA at 1 hour after instillation, in 71% and 56% of treated patients, respectively (p<0.0001, for both comparison).

• Both the LNZ100 and LNZ101 formulations maintained the 3-line (15 letters) or greater improvement significance compared to the vehicle for all timepoints including the last measurement performed at 10 hours after instillation in 37% and 48% of treated patients, respectively (p<0.0012 and p<0.0002, respectively).

The key secondary endpoint of a 2-line (10 letters) or greater improvement in near VA without loss of 1 line (5 letters) or more of distance vision showed responder rates of 86% and 78%, respectively, 1 hour after treatment, and 55% and 58% at 10 hours after treatment.

• Both formulations maintained an average pupil size of 1.5 to 2 mm for 10 hours, the company reported today.

The 2 investigational formulations of aceclidine evaluated to treat presbyopia, LNZ100 (aceclidine) and LNZ101 (aceclidine + brimonidine), achieved the primary study endpoint without a loss of distance VA 1 hour after instillation in 71% and 56% of treated subjects respectively, compared to 6% of subjects treated with the vehicle, the company reported in a press release.

The maintenance of the average pupil size of 1.5 to 2 mm for 10 hours is a biomarker of the formulations’ efficacy. Both formulations demonstrated rapid onset of action with 73% and 62% of treated patients achieving a 3-line or greater improvement within 30 minutes for LNZ100 and LNZ101 respectively, compared to 8% for vehicle.

Feedback from the patients treated with the active formulations indicated that both were well-tolerated and there were no serious drug-related adverse events.

Based on these positive outcomes, the company plans to start phase 3 pivotal trials shortly.

“We know that the majority of presbyopia patients are looking for a product that is highly effective in improving near vision for their full workday. Our best-in-class results clearly reflect this ideal profile, with 10-hour efficacy, and further extends our potential for category leadership,” according to Eef Schimmelpennink, President and CEO of LENZ. “I look forward to our upcoming pivotal trials.”

INSIGHT Phase 2 Trial

The INSIGHT trial (NCT05294328) was a multicenter, double-masked, randomized, crossover, active and vehicle-controlled, safety and efficacy study with a study population that ranged in age from 46 to 73 years and a range of refractive errors from -3.25 diopters (D) of spherical equivalent (SE) to +1.5 D SE.

The trial enrolled 67 subjects, including some who had undergone a previous vision correction or who were pseudophakic.