Lenz Therapeutics, Inc. reported that the FDA has accepted its new drug application (NDA) for LNZ100 (1.75% aceclidine), an investigational ophthalmic solution intended to treat presbyopia.
Exciting news! Let’s just dive right in with LNZ100.
The candidate is a preservative-free, single-use, once-daily eye drop formulated with a key ingredient: Aceclidine.
What this is: A small-molecule muscarinic acetylcholine receptor agonist that can cause miosis, potentially resulting in a “pinhole” effect to improve near vision and prevent a myopic shift.
What data supports this key ingredient?
Its long-standing efficacy can be traced back to 1975, when its accommodative effects were studied for the treatment of open-angle glaucoma (OAG) and published in the American Journal of Ophthalmology.
As a bonus: Aceclidine has been marketed for use in Europe for 50+ years—but never clinically used in the United States.
- And take note: The chemical entity is not approved for presbyopia treatment in any country.
Interesting … speaking of clinical findings, talk about LNZ100’s data.
Key in supporting this NDA submission was Lenz’s phase 3 CLARITY program (conducted in collaboration with ORA, Inc.)
The program encompassed two 6-week efficacy trials evaluating LNZ100 as well as LNZ101 (1.75% aceclidine, Lenz’s second investigational candidate for presbyopia):
- CLARITY 1 (NCT05656027)
- CLARITY 2 safety study (NCT05753189)
What was measured during these trials?
The studies’ primary outcome measures included:
- CLARITY 1: Participants who achieved a 3-line or greater improvement from baseline in the study eye with no loss in best-corrected distance visual acuity (BCDVA) at 5 letters or more of distance vision (at 4 months)
- Measured at 3 hours post-treatment
- CLARITY 2: Participants who experienced adverse events (AEs) and monocular BCDVA changes at 4 months
- Measured at seven clinic visits or a total duration of 28 weeks (approximately)
And the findings?
Reported just this past March, LNZ100 achieved its primary and secondary near-vision improvement endpoints in both studies.
Broken down by trial:
- CLARITY 1: 64% and 83% of participants achieved three- and two-lines or greater improvement, respectively
- CLARITY 2: 71% and 91% of participants achieved three- and two-lines or greater improvement, respectively
In regards to tolerance: The eye drop was well tolerated and had no serious treatment-related AEs observed following “over 30,000 treatment days.”
So … what happens next?
The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date for Aug. 8, 2025, according to the company.
Lenz also noted that the FDA has no plans for an advisory committee meeting—which typically reviews and provides independent advice relating to the quality of its regulatory decision-making on NDAs—to discuss this particular NDA.
- Important to note: While often required for a drug indication first in its class, these meetings are not mandatory for all NDAs.
If approved next August, Lenz President and CEO Eef Schimmelpennink noted an anticipated (potential) launch of LNZ100 as early as H2 2025.
Lastly, what’s the big picture of this?
With the company looking to “establish LNZ100 as the standard of care eye drop for the treatment of presbyopia,” according to COO Shawn Olson, Schimmelpennink has previously called out the formulation’s potential as a “pupil-selective and long-lasting therapeutic option” for treating presbyopia.
And on that note: See what’s new in the clinical developments of presbyopia treatment.