WOW! WHAT A YEAR IN THE PRESBYOPIA PIPELINE.
The prospects of topical presbyopia options are growing, the marketing dynamics are shifting, and the landscape of treatment options is evolving.
Serving 120,000 patients with 190,000 prescriptions filled, and counting, Vuity (pilocarpine hydrochloride ophthalmic solution 1.25%) made a splash in 2022 as the first available topical eye drop treatment for presbyopia.1,2 As primary eye care providers responsible for managing the majority of refractive errors with spectacle and contact lens correction, it is no surprise that nearly 75% of Vuity prescriptions have been written by optometrists.1,2
By increasing the depth of focus via pupil constriction, Vuity demonstrates improvement with near and intermediate vision in as little as 15 minutes, lasting up to 6 hours with once-daily dosing.2 FDA approval of Vuity was based on two phase 3 studies (GEMINI-1 and GEMINI-2), in which the primary endpoints included a statistically significant proportion of participants gaining 3 lines of improvement at near, without losing more than 1 line of corrected distance visual acuity (CDVA) at day 30, hour 3, versus placebo.2
Allergan has announced positive topline results of an additional P3 trial (VIRGO) evaluating the efficacy and safety of twice-daily administration of Vuity, improving near vision without compromising distance vision at hour 9 (3 hours after the second drop) on day 14.2 The final results have not yet been published.
Orasis is on track to be next to market, with recent FDA acceptance of its NDA. CSF-1 (0.4% pilocarpine ophthalmic solution) is a preservative-free topical presbyopia treatment that will be available with a dosing schedule that provides the patient flexibility to add a second dose after 3 or 4 hours to extend the effect out to 8 hours, if desired.3 Two P3 studies (NEAR-1 and NEAR-2) have wrapped up with results showing CSF-1 to be well tolerated among patients, with a safety profile that does not compromise distance or night vision.3
The P3 trials confirmed the primary and key secondary endpoint goals of a 3-line or more improvement in distance-corrected near vision acuity (DCNVA) without loss of best-corrected distance visual acuity (BCDVA).3 Participants were dosed twice daily on both eyes at an interval of 2 hours between doses on days 1-8 and an interval of 3 hours on days 8-15.3 On day 15, participants achieved statistically significant 3-line improvement in as early as 20 minutes and lasting up to 8 hours after the first dose.3
Notably, these results were achieved with a minimal effective dose of pilocarpine, which is less than one-third the concentration of the only commercially available treatment.3 More new data on CSF-1 will be presented at SECO. Orasis anticipates an approval in quarter 4 of 2023 and plans to launch in early 2024.
Eyenovia offers a unique presbyopia treatment option that includes a proprietary spray dispenser (Optejet) with Microdose Array Print (MAP) technology. Allowing for less waste, decreased exposure to preservatives, and a convenient spray (no need to tilt the head back), this option provides an alternative administration of pilocarpine.4,5
The third P3 study (VISION-1) evaluated the safety and efficacy of the 2 formulations, pilocarpine 1% and 2%.4 In October 2022, Eyenovia announced positive results of the fourth P3 trial (VISION-2) confirming the safety and efficacy of MAP with a primary endpoint of improved high-contrast binocular distance corrected visual acuity (DCVA) in low light conditions 2 hours after treatment using MicroLine 2%.5
Notably, proprietary market research by Eyenovia has also revealed that nearly 80% of patients 40-55 year old who otherwise would not have worn glasses would prefer the Optejet device over traditional drops.5
Brimochol (Visus Therapeutics)
Utilizing a synergistic effect, Brimochol brings together a combination of carbachol (a cholinergic agent) and brimonidine tartrate (an alpha-2 agonist).6,7 The 2 active ingredients constrict the iris sphincter and inhibit iris dilator contraction, helping to create a pinhole effect.6,7
After positive results of the P2 studies (VIVID), Visus announced P3 trials (BRIO-I and BRIO-II) to evaluate the safety and efficacy of Brimochol PF.6,7 Measuring data in emmetropic phakic and pseudophakic presbyopia patients, the primary efficacy endpoint is the percentage of patients who gain 3 lines of improvement in binocular near visual acuity without losing 1 line of distance vision.6,7
P3 studies are still ongoing. Visus is hopeful for a launch in 2025.
|FDA approved (QD dosing). Trials for investigational BID dosing ongoing.|
|P3 complete, NDA accepted by the FDA.|
|P3 complete, awaiting NDA submission.|
|Nyxol, and Nyxol + low-dose pilocarpine||Ocuphire Pharma||
|P3 planned, accepting enrollment.
1-year safety study planned.
|P2 complete, P3 planned.|
Nyxol, and Nyxol + Low-dose Pilocarpine (Ocuphire Pharma)
Ocuphire has studied combinations of Nyxol 0.75% phentolamine (or 1% phentolamine mesylate) and 0.4% low-dose pilocarpine (LDP), in addition to Nyxol alone. Nyxol ophthalmic solution is a nonselective alpha adrenergic antagonist offered in a preservative-free formulation that acts on the iris dilator muscle, decreasing pupil diameter and inhibiting the contraction of the smooth muscle of the iris.8,9 Creating a “pinhole effect,” the smaller pupil leads to increased depth of focus with rapid onset of action and sustained duration of effect.8
In the VEGA-1 P2 trial, Ocuphire validated the effects of Nyxol dosed before bedtime and LDP (which activates the iris sphincter muscle) dosed during the daytime.8,9 With 61% of subjects gaining 3 lines of near vision at 1 hour, Ocuphire achieved primary endpoints of P2 and showed a favorable safety profile.8,9 Positive results were also reported with Nyxol alone and more studies have been planned.8,9
As of January 2023, Ocuphire had reported enrollment of the first patients for the VEGA-2 P3 trials.9 Following VEGA-2, Ocuphire plans to initiate a second P3 trial (VEGA-3) and a 1-year safety study (LYRA-1).8,9
LNZ100 and LNZ101 (Lenz Therapeutics)
Headquartered in California, Lenz Therapeutics is undertaking testing for 2 investigational preservative-free formulations of aceclidine: LNZ100 (1.75% aceclidine) and LNZ101 (1.75% aceclidine + brimonidine).10
Aceclidine (a muscarinic acetylcholine receptor agonist) is a parasympathomimetic miotic that alters pupil size by targeting the iris sphincter.10 The formulation by Lenz Therapeutics demonstrates the ability to influence the pupil size with minimal effect on the ciliary muscle (compared to pilocarpine and carbachol).10
The topline results of the P2 trials (INSIGHT) included participants ranging in ages from 46 to 73, consisting of some patients with prior vision correction and pseudophakia.10 Both LNZ100 and LNZ101 achieved the primary endpoint of 3-line or greater improvement in near visual acuity, without losing 1 line or more in distance visual acuity at 1 hour.10 The primary endpoint was met in 71% and 56% of treated subjects, respectively, compared to 6% of vehicle-treated subjects.10 ■
- Waring GO 4th, Price FW Jr, Wirta D, et al. Safety and Efficacy of AGN-190584 in Individuals With Presbyopia: The GEMINI 1 Phase 3 Randomized Clinical Trial. JAMA Ophthalmol. 2022;140(4):363-371. doi:10.1001/jamaophthalmol.2022.0059
- Allergan, an AbbVie company, announces positive topline phase 3 results evaluating investigational twice-daily administration of VUITY™ (pilocarpine HCl ophthalmic solution) 1.25% in adults with age-related blurry near vision (presbyopia). AbbVie News Center. April 5, 2022. Accessed February 5, 2023. https://news.abbvie.com/news/press-releases/allergan-an-abbvie-company-announces-positive-topline-phase-3-results-evaluating-investigational-twice-daily-administration-vuity-pilocarpine-hci-ophthalmic-solution-125-in-adults-with-age-related-blurry-near-vision-presbyopia.htm
- Orasis Pharmaceuticals. Accessed February 5, 2023. https://www.orasis-pharma.com/
- Eyenovia announces positive topline results from VISION-1 phase 3 clinical study of MicroLine for the treatment of presbyopia. Eyenovia. May 25, 2021. Accessed February 5, 2023. https://eyenovia.com/eyenovia-announces-positive-topline-results-from-vision-1-phase-3-clinical-study-of-microline-for-the-treatment-of-presbyopia/
- Eyenovia announces positive results from VISION-2 Phase 3 Study of MicroLine as a potential on-demand treatment for presbyopia. Eyenovia. October 20, 2022. Accessed February 5, 2023. https://eyenovia.com/eyenovia-announces-positive-results-from-vision-2-phase-3-study-of-microline-as-a-potential-on-demand-treatment-for-presbyopia/
- Visus Therapeutics initiates phase 2 clinical trial of Brimochol for the treatment of presbyopia. Visus Therapeutics. March 25, 2021. Accessed February 5, 2023. https://uploads-ssl.webflow.com/5eea6cf86d23885e6fe09eb2/605be3ce5d20506c04b99ca9_Visus%20Therapeutics_PRESS%20RELEASE_FirstPatientPh2_FINAL%20FOR%20BW%20UPLOAD%203.24.2021.pdf
- Visus Therapeutics reports positive phase 2 results for three presbyopia formulations. Ocular Surgery News. December 1, 2021. Accessed February 5, 2023. https://www.healio.com/news/ophthalmology/20211201/visus-therapeutics-reports-positive-phase-2-results-for-three-presbyopia-formulations
- Ocuphire’s VEGA-1 phase 2 trial in presbyopia meets primary and secondary endpoints. Ocuphire Pharma. June 30, 2021. Accessed February 5, 2023. https://www.ocuphire.com/news-media/press-releases/detail/344/ocuphires-vega-1-phase-2-trial-in-presbyopia-meets
- Nyxol Eye Drops. Ocuphire website product pipeline page. https://www.ocuphire.com/product-pipeline/nyxol
- Lenz Therapeutics announces positive topline data from phase 2 INSIGHT trial of LNZ100 and LNZ101 to treat presbyopia. Lenz Therapeutics. October 18, 2022. Accessed February 5, 2023. https://lenz-tx.com/2022/10/lenz-therapeutics-announces-positive-topline-data-from-phase-2-insight-trial-of-lnz100-and-lnz101-to-treat-presbyopia/