In October of 2021, Vuity (pilocarpine hydrochloride ophthalmic solution 1.25%; Allergan, AbbVie) became the first FDA-approved eye drop to treat presbyopia in adults. Several other pharmaceutical manufacturers have been developing their own topical formulations over the ensuing years, with Qlosi (pilocarpine hydrochloride ophthalmic solution 0.4%; Orasis Pharmaceuticals) receiving approval in 2023. As of press time, only Vuity has been brought to market, but the pipeline is flowing. Here is an update on this expanding category.1-3
FDA-Approved Drops
Vuity (pilocarpine hydrochloride ophthalmic solution 1.25%; AbbVie) is a cholinergic muscarinic agonist that stimulates the iris sphincter and ciliary to contract, constricting the pupil and improving near and intermediate visual acuity while maintaining some pupillary responsiveness to light. In 2 pivotal phase 3 trials, GEMINI 1 and 2, patients gained at least 3 three lines of improvement in their mesopic, high-contrast, binocular distance-corrected near visual acuity (DCNVA) without losing more than 1 line of corrected distance visual acuity (CDVA) at day 30. The drug is most effective for individuals with early presbyopia and minimal refractive errors. It typically takes effect within 15 minutes of administration and lasts about 6 to 8 hours.1-2
In 2023, the FDA approved twice- daily application of Vuity after the VIRGO phase 3 trial demonstrated a statistically significant increase in patients achieving the primary and secondary endpoints with the twice-daily dosage vs once-daily dosage. The safety profile was consistent with that of Vuity once daily, with minimal systemic accumulation.3
Side effects of Vuity can include headaches and blurred vision from accommodative spasm, as well as eye irritation. In rare cases, the drug was associated with retinal detachment and retinal tear. It may not be suitable for patients with advanced presbyopia or cataracts, and it is not recommended for patients over age 55.1-3
Qlosi (pilocarpine hydrochloride ophthalmic solution 0.4%; Orasis Pharmaceuticals) is a cholinergic agonist indicated for the treatment of presbyopia in adults. It received FDA approval in 2023 but did not secure funding for a commercial launch until late 2024.4-5 At press time, it was not yet on the market.
Qlosi contains a lower dose of pilocarpine hydrochloride than Vuity but has the same mechanism of action, with similar benefits and side effects. It is packaged in disposable, single-use vials, eliminating the need for antimicrobial preservatives that can damage the ocular surface. Like Vuity, in pivotal clinical trials (NEAR 1 and 2), Qlosi met its primary endpoints of a 3-line gain in DCNVA without the loss of 1 line in CDVA; demonstrated efficacy within 15 to 20 minutes of administration; and lasted up to 8 hours.4-5
Side effects of Qlosi can include headaches and blurred vision, as well as eye irritation and eye pain. Some users may experience decreased night vision. Qlosi is not suitable for individuals with iritis or a history of retinal detachment.4-5
Drops Pending NDA & PDUFA
As of press time, 2 presbyopia drugs have met their primary endpoints in phase 3 clinical trials and moved into the FDA’s new drug application (NDA) phase.
LNZ100 (aceclidine 1.75%; LENZ Therapeutics) is a preservative-free ophthalmic solution that works as a pupil-selective miotic to improve near vision without inducing a myopic shift.6-8 Specifically, it can activate the iris sphincter muscle to cause miosis of the pupil to a diameter below 2 mm, without overstimulating the ciliary muscles and impairing distance vision—making it possible for older presbyopes to benefit from the drug. Side effects of LNZ100 may include eye irritation, visual impairment, and headache.6-8
In April 2024, LENZ Therapeutics announced that its phase 3 CLARITY clinical trial of LNZ100 had met its primary endpoint, with 71% of patients who received the drug achieving 3 lines or greater improvement at 30 minutes, and 40% maintaining that acuity at 10 hours. In October 2024, the FDA accepted the company’s new drug application (NDA) for LNZ100 and assigned it a Prescription Drug User Fee Act (PDUFA) target action date of August 8, 2025.6-8
Brimochol PF (carbachol 2.75% and brimonidine tartrate 0.1%; Tenpoint Therapeutics) is a preservative- free ophthalmic solution that combines carbachol (a miotic agent for pupil constriction) and brimonidine tartrate (a sympatholytic alpha-2 agonist that prevents pupil dilation) to improve near visual acuity while minimizing side effects.9-10
Two phase 3 clinical trials, BRIO-I and BRIO-II, have achieved their primary endpoints of demonstrating statistically significant improvements in near vision vs vehicle at all timepoints out to 8 hours (P<.008), paving the way for Tenpoint Therapeutics to file its NDA. The company hopes to launch Brimochol PF in the first half 2026.9-10
Knowing that brimonidine tartrate inhibits iris dilator muscle contraction, investigators hypothesized that it might also inhibit contraction of the ciliary muscle by activating alpha-2 receptors—potentially mitigating the side effects commonly associated with miotics, such as headache. Furthermore, brimonidine tartrate may increase the bioavailability of carbachol by altering aqueous dynamics, prolonging pupil constriction and the duration of improved near vision. 9-10
These mechanisms could make Brimochol PF a key solution for patients over 55 with emmetropic phakic or pseudophakic presbyopia.
Phase 3 Trial Under Way
Ryzumvi (phentolamine ophthalmic solution 0.75%; Opus Genetics) is a preservative-free, nonselective alpha-1 and alpha-2 adrenergic antagonist designed to reduce pupil size. Formerly known as Nyxol, it was originally approved by the FDA in 2023 for the reversal of pharmacologically induced mydriasis.11-12 Ryzumvi, which blocks alpha-1 receptors on the radial iris dilator muscles without affecting the ciliary muscle, is now being investigated as a treatment for presbyopia. As of press time, phase 3 of the drug’s VEGA-3 trial was under way.11-12 OM
References
1. U.S. Food and Drug Administration approves Vuity (pilocarpine HCI ophthalmic solution) 1.25%, the first and only eye drop to treat presbyopia (age-related blurry near vision). News release. Abbvie. October 21, 2021. Accessed February 17, 2025. https://news.abbvie.com/2021-10-29-U-S-Food-and-Drug-Administration-Approves-VUITY-TM-pilocarpine-HCI-ophthalmic-solution-1-25-,-the-First-and-Only-Eye-Drop-to-Treat-Presbyopia-Age-Related-Blurry-Near-Vision.
2. Lievens CW, Hom MM, McLaurin EB, Yuan J, Safyan E, Liu H. Pilocarpine HCl 1.25% for treatment of presbyopia after laser vision correction: pooled analysis of two phase 3 randomized trials (GEMINI 1 and 2). J Cataract Refract Surg. 2024;50(1):57-63. doi:10.1097/j.jcrs.0000000000001313
3. Kannarr S, El-Harazi SM, Moshirfar M, et al. Safety and efficacy of twice-daily pilocarpine HCl in presbyopia: the VIRGO phase 3, randomized, double-masked, controlled study. Am J Ophthalmol. 2023;253:189-200. doi:10.1016/j.ajo.2023.05.008
4. Orasis Pharmaceuticals completes $78 million financing to support commercial launch of Qlosi (pilocarpine hydrochloride ophthalmic solution) 0.4%. News release. Orasis Pharmaceuticals. October 8, 2024. Accessed February 14, 2025. www.prnewswire.com/news-releases/orasis-pharmaceuticals-completes-78-million-financing-to-support-commercial-launch-of-qlosi-pilocarpine-hydrochloride-ophthalmic-solution-0-4-302269236.html
5. Holland E, Karpecki P, Fingeret M, et al. Efficacy and safety of CSF-1 (0.4% pilocarpine hydrochloride) in presbyopia: Pooled results of the NEAR phase 3 randomized, clinical trials. Clin Ther. 2024;46(2):104-113. doi:10.1016/j.clinthera.2023.12.005
6. CORXEL and LENZ Therapeutics announce positive topline data from China phase 3 presbyopia trial of LNZ100. News release. LENZ Therapeutics. October 27, 2024. Accessed February 13, 2025. https://ir.lenz-tx.com/news-events/press-releases/detail/23/corxel-and-lenz-therapeutics-announce-positive-topline-data-from-china-phase-3-presbyopia-trial-of-lnz100.
7. LENZ Therapeutics announces positive topline data from phase 3 CLARITY presbyopia trials. News release. LENZ Therapeutics. April 3, 2024. Accessed February 13, 2025. https://ir.lenz-tx.com/news-events/press-releases/detail/11/lenz-therapeutics-announces-positive-topline-data-from-phase-3-clarity-presbyopia-trials.
8. LENZ Therapeutics announces FDA acceptance of new drug application for LNZ100 for the treatment of presbyopia. News release. LENZ Therapeutics. October 21, 2024. Accessed February 13, 2025. https://ir.lenz-tx.com/news-events/press-releases/detail/22/lenz-therapeutics-announces-fda-acceptance-of-new-drug-application-for-lnz100-for-the-treatment-of-presbyopia.
9. Abdelkader A, Kaufman HE. Clinical outcomes of combined versus separate carbachol and brimonidine drops in correcting presbyopia. Eye Vis (Lond). 2016;3:31. Published 2016 Dec 5. doi:10.1186/s40662-016-0065-3
10. Tenpoint Therapeutics announces positive topline data from phase 3 pivotal study, BRIO-II, of Brimochol PF for the treatment of presbyopia. News release. Tenpoint Therapeutics. January 8, 2025. Accessed February 12, 2025. https://www.businesswire.com/news/home/20250109824922/en/Tenpoint-Therapeutics-Announces-Positive-Topline-Data-from-Phase-3-Pivotal-Study-BRIO-II-of-BRIMOCHOL-PF-for-the-Treatment-of-Presbyopia
11. Pepose JS, Hartman PJ, DuBiner HB, et al. Phentolamine mesylate ophthalmic solution provides lasting pupil modulation and improves near visual acuity in presbyopic glaucoma patients in a randomized phase 2b clinical trial. Clin Ophthalmol. 2021;15:79-91. Published 2021 Jan 8. doi:10.2147/OPTH.S278169
12. Patel R, Brigell MG, Pepose JS, et al. VEGA-1 phase 2 trial: phentolamine ophthalmic solution maintains pupillary light reflex with improved distance-corrected near vision in presbyopes. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2507.