Ocuphire’s VEGA-1 Phase 2 Trial in Presbyopia Meets Primary and Secondary Endpoints

Ocuphire Pharma announced that the VEGA-1 phase 2 clinical trial evaluating the efficacy and safety of Nyxol in combination with low-dose pilocarpine (LDP) in presbyopic subjects successfully met its primary and many secondary endpoints. On the strength of these results, Ocuphire plans to move into phase 3.

Given the rapid onset and sustained duration of efficacy, the favorable safety profile, and the potential tunability of treatment, Nyxol + LDP has the potential for differentiation and to be a best-in-class product for the treatment of presbyopia, according to Ocuphire.

Highlights from the VEGA-1 Phase 2 Trial in Presbyopia:

Nyxol + LDP Met the Primary Endpoint

• 61% of subjects treated with Nyxol + LDP improved 15 letters or greater (≥ 3 lines) in photopic binocular near vision at 1 hour compared with 28% of subjects on placebo with statistical significance (p = 0.003 with placebo adjusted difference of 33%)

Nyxol + LDP Met Many Additional Efficacy Endpoints

• Met the phase 3 co-primary endpoint vs. placebo gaining 15 letters (3 lines) near vision with less than 5 letters of distance vision loss
• Rapid onset of efficacy at 30 mins
• Durable near vision improvement through at least 6 hours
• Sustained significant reduction in pupil diameter over at least 18 hours due to the durable effects of Nyxol
• Near vision efficacy seen both monocularly and binocularly
• Efficacy in both light and dark iris colors

Nyxol + LDP Showed a Favorable Safety Profile

• No serious AEs, almost all AEs were mild
• No headaches, no brow aches, and no blurry vision AEs were reported
• Mild, transient conjunctival hyperemia (eye redness) observed in <5% of subjects

Jay S. Pepose, MD, PhD, Director of the Pepose Vision Institute, Professor of Clinical Ophthalmology at the Washington University School of Medicine, and Ocuphire Medical Advisory Board and Corporate Board member, commented, “The results from this phase 2 VEGA-1 trial validate Nyxol’s mechanism of action on iris dilator muscle and the beneficial effects of smaller pupil size in treating presbyopia. These latest data support a clinical profile for Nyxol plus LDP combination that includes rapid onset of action and sustained duration of effect, while maintaining distance visual acuity in day and night conditions. All treatments were well tolerated and demonstrated a favorable safety profile. Taken together, we believe these attributes position Nyxol + LDP as a potential ‘best in class’ presbyopia treatment option.”

Susan Benton of Ocuphire’s Board of Directors remarked, “The need for an eyedrop treatment is highlighted by industry leader Allergan and several other companies developing pharmacological treatment options for presbyopia. Ocuphire’s novel target product profile of a combination kit of Nyxol and LDP may offer rapid onset and long-lasting effects with ‘tunability’ as an option in that all patients are not the same (one size does not fit all). A combination kit option may provide a “range” of pupillary modulation that the doctor can customize to the patient to optimize their near vision. This ability to customize therapy will be more difficult for fixed-dose combinations and single-agent products.”

“We are thrilled with the positive outcome in VEGA-1, which showed that a combination of Nyxol and low-dose pilocarpine produced a statistically significant improvement in near visual acuity in subjects with presbyopia,” said Mina Sooch, MBA, President and CEO of Ocuphire Pharma. “We would like to thank all of the subjects and investigational sites that participated in our first presbyopia clinical trial for Nyxol. Presbyopia represents an area of considerable unmet need due to its rising prevalence worldwide and the limitations of currently available corrective methods. Based on the data generated thus far, we believe that Nyxol and LDP is novel in its mechanism of action and could become a leading pharmacological treatment option for presbyopia and potentially allow those afflicted to reduce their dependence on reading glasses. We plan to initiate our phase 3 trials for presbyopia in 2022, building on our recent success of Nyxol for Reversal of Mydriasis with the initiation of the second phase 3 registration trial later this year.”

VEGA-1 Phase 2 Trial Design 

The VEGA-1 phase 2 clinical trial was designed to evaluate the efficacy and safety of Nyxol in combination with low-dose pilocarpine compared to placebo in presbyopic subjects. A total of 150 subjects (planned target was 140 to 152) were enrolled at 17 investigational sites in the US from mid-February to mid-May of this year. The phase 2 trial was a randomized, double-masked, placebo-controlled study with 4 treatment arms. At the first visit, subjects were randomized to receive either Nyxol or placebo drops that were instilled at home near bedtime for 3 to 4 days prior to Visit 2; at Visit 2 subjects then received either low-dose pilocarpine or no treatment, with efficacy and safety measurements collected at multiple time points through 6 hours. The primary endpoint was the percentage of subjects with ≥ 15 letters of improvement in photopic binocular near vision (i.e. distance-corrected near visually acuity, DCNVA) at 1 hour on Visit 2 for Nyxol + LDP arm compared to placebo alone arm. The study was powered for comparison to placebo whereas comparison to component arms were designed to inform the phase 3 sample size for a combination product approval. Secondary endpoints at multiple timepoints included Nyxol + LDP improvements of 3 lines of DCNVA without any loss of distance vision, pupil diameter, and improvements of DCNVA of 1 and 2 lines compared to placebo as well as to Nyxol and low-dose pilocarpine alone. For more information, refer to ClinicalTrials.gov Identifier: NCT04675151.

Ocuphire collaborated closely with Oculos Development Services, a Rush, NY-based clinical research organization and a subsidiary of iuvo BioScience, on the launch and execution of the VEGA-1 trial.

Detailed results of the VEGA-1 study will be presented by Dr. Pepose at the upcoming American Society of Cataract and Refractive Surgery (ASCRS) medical meeting: VEGA-1 Presbyopia Presentation on Sunday, July 25, 2021, at 8:45 am (ASCRS Paper ID 76645).