Just days following the FDA’s acceptance of its new drug application (NDA), LENZ Therapeutics, Inc.—in collaboration with Corxel Pharmaceuticals—announced positive topline data from the China-based phase 3 clinical trial investigating LNZ100 (1.75% aceclidine HCl) for the treatment of presbyopia.
First, a rundown on these companies.
LENZ is a San Diego, California-based late-stage biopharmaceutical company working to develop and potentially commercialize therapeutics for vision improvement—with a focus on presbyopia.
- As a refresh: LENZ merged with Graphite in March 2024 under one name (LENZ) to advance two key presbyopic therapies, formulated as eye drops:
- LNZ100 (1.75% aceclidine; our topic of interest )
- LNZ101 (1.75% aceclidine and brimonidine)
Next: CORXEL
Previously known as Ji Xing Pharmaceuticals and launched in 2019, CORXEL is a U.S.- and China-headquartered biotech company targeting the development and commercialization of therapeutics for serious and life-threatening cardiometabolic diseases.
Its pipeline: Consists of global assets for hypertension and acute ischemic stroke (AIS), while its Greater China assets include:
- LNZ100 (parasympathomimetic miotic agent) for presbyopia
- Rights acquired from LENZ in April 2022
- Tyrvaya (varenicline solution nasal spray) for dr eye disease (DED)
- Rights acquired from Oyster Point Pharma, Inc., a Viatris company, in February 2021
Zero in on LNZ100.
LNZ100 is formulated with aceclidine and is a preservative-free, single-use, once-daily eye drop intended to treat presbyopia.
In case you forgot: Aceclidine is a small-molecule muscarinic acetylcholine receptor agonist that can cause miosis, which might result in a “pinhole” effect to improve near vision and prevent a myopic shift.
- Note: While not currently approved for presbyopia in any country, aceclidine is indicated for the treatment of open-angle glaucoma (OAG) in Europe.
And its U.S. status?
As we mentioned, the FDA quite literally just accepted LENZ’s NDA and assigned a Prescription Drug User Fee Act (PDUFA) target action date of Aug. 8, 2025.
If all goes well and the formulation is approved, LENZ anticipates launching LNZ100 as early as H2 2025.
Gotcha. Now to this phase 3 study.
The multicenter, randomized, double-blind, vehicle-controlled study consisted of two additional trials:
- A 4-week efficacy study, followed by
- A 5-month extension safety study
The participants: 300 patients (aged 45 to 75) with a refractive range of -4.0D SE to +1.0D SE
- This included those patients who previously underwent laser-assisted cornea refractive surgery/monofocal intraocular (IOL) implantation
The objective: To evaluate the potential of LNZ100 in improving near vision as well as identify the efficacy and safety profiles.
And the findings?
Overall, the study met its primary and key secondary endpoints.
The data: A “statistically significant 3-lines or greater improvement in best-corrected distance visual acuity (BCDVA) at near” was observed, while the optimal distance VA (in other words: not losing 5+ letters) was also observed.
What else?
LNZ100 also demonstrated rapid onset and long duration, as noted in the following (all p < 0.0001):
- At 30 minutes post-treatment: 84% and 69% of patients achieved 2-lines and 3-lines or greater improvement, respectively
- At 3 hours post-treatment: 88% and 74% of patients achieved 2-lines and 3-lines or greater improvement, respectively
- At 10 hours post-treatment: 61% and 30% of patients achieved 2-lines and 3-lines or greater improvement, respectively
How was LNZ100 tolerated?
The candidate was “well-tolerated,” with investigators observing no serious treatment-related adverse events (TRAEs).
How does this compare to prior U.S. clinical trial findings?
Back in April 2024, LENZ reported similar promising data from the phase 3 CLARITY program (consisting of two 6-week efficacy trials).
See here for those details, observed at 30 minutes, 3 hours, and 10 hours post-administration of LNZ100.
And the investigators’ feedback on this latest data?
Based on the “statistically significant data and clinically meaningful outcomes” noted in the trial, Fan Lyu, principal investigator and co-principal investigator, stated that LNZ100 is expected to be a “practical treatment option for a wide spectrum of patients.”
And what’s next?
CORXEL CEO and Board Executive Director Sandy Mou stated that the company intends to communicate and cooperate with drug regulatory authorities to support an expedited submission and approval of LNZ100.
“With this data, we believe LNZ100 has further enhanced its potential as a global therapy and is further on its path towards providing access to the estimated 400 million people with presbyopia in China,” Mou concluded.