Opus Genetics Announces LYNX-2 Phase 3 Trial Met its Primary Endpoint for Phentolamine Ophthalmic Solution 0.75% in Keratorefractive Patients with Visual Disturbances Under Mesopic, Low-Contrast Conditions

Rhea-AI Summary

Opus Genetics (NASDAQ: IRD) announced positive Phase 3 trial results for Phentolamine Ophthalmic Solution 0.75%, designed to treat night driving impairment in keratorefractive surgery patients. The LYNX-2 trial met its primary endpoint, with 17.3% of treated patients achieving ≥15-letter improvement in mesopic low contrast distance visual acuity compared to 9.2% in the placebo group (p<0.05). The drug, which reduces pupil diameter through a sympatholytic mechanism, demonstrated significant benefits for patients experiencing vision disturbances like glare and halos under low-light conditions. The study, conducted under FDA Special Protocol Assessment and Fast-Track Designation, showed consistent safety profile with previous trials and no tachyphylaxis over 6 weeks. Opus has a global licensing agreement with Viatris for commercialization rights in the U.S.

Positive

• Met primary endpoint with statistically significant improvement in mesopic low contrast distance visual acuity
• First potential FDA-approved therapy for keratorefractive patients with night vision disturbances
• Demonstrated patient-reported functional benefits in night driving vision
• FDA Fast-Track Designation and Special Protocol Assessment agreement in place
• No evidence of tachyphylaxis observed over 6-week period
• Consistent safety profile with no new safety signals identified

Negative

• Only 17.3% of treated patients achieved the target vision improvement
• Long-term safety data beyond 6 weeks still pending

Insights

Ophthalmology Clinical Research Expert

Opus's Phentolamine eye drops show significant efficacy for night vision problems after LASIK, meeting Phase 3 endpoints for a currently untreatable condition.

The LYNX-2 Phase 3 results represent a significant clinical advancement for post-keratorefractive surgery patients suffering from nighttime visual disturbances. The primary endpoint achievement is particularly noteworthy—17.3% of treated patients achieved a ≥15-letter improvement in mesopic low contrast distance visual acuity compared to 9.2% for placebo (p<0.05).

What's clinically important here is the mechanism of action. Phentolamine's sympatholytic approach reduces pupil size without engaging the ciliary muscle, avoiding the retinal tear/detachment risks associated with older parasympathomimetic agents. This creates a more favorable safety profile for long-term use in this chronic condition.

The patient-reported outcomes on night driving function are particularly compelling. Patients reported statistically significant improvements in ability to see despite oncoming headlights and reduced glare sensitivity at dawn/dusk—functional benefits that translate to meaningful quality-of-life improvements.

The absence of tachyphylaxis through 6 weeks suggests sustained efficacy without tolerance development, addressing a common concern with chronic ophthalmic medications. The FDA's grant of both Special Protocol Assessment and Fast-Track designation further validates the unmet need this therapy addresses—currently, no FDA-approved treatment exists for this common post-surgical complication that affects quality of life for millions who've undergone LASIK, PRK, SMILE, or RK procedures.

• Study met primary endpoint of ≥15-letter (≥3-line) gain in mesopic low contrast distance visual acuity in comparison to placebo
  
  
• Phase 3 study showed patient-reported functional benefit in treating significant, chronic night driving impairment in keratorefractive patients with reduced mesopic vision, a condition with no current FDA-approved therapies
  
  
• Safety profile consistent with previous studies, with no new safety signals identified
  
  
• No evidence of tachyphylaxis was observed in this study over the 6-week period
  
  
• Study was conducted under FDA Special Protocol Assessment and Fast-Track Designation
  
  

RESEARCH TRIANGLE PARK, N.C., June 02, 2025 (GLOBE NEWSWIRE) -- Opus Genetics, Inc. (Nasdaq: IRD), a clinical-stage biopharmaceutical company developing gene therapies for the treatment of inherited retinal diseases (IRDs) and small molecule therapies for other ophthalmic disorders, today announced positive topline results from LYNX-2, a pivotal Phase 3 clinical trial evaluating Phentolamine Ophthalmic Solution 0.75% for the treatment of significant, chronic night driving impairment in keratorefractive patients with reduced mesopic vision.

Patients who undergo keratorefractive procedures such as Laser-Assisted In Situ Keratomileusis (LASIK), Photorefractive Keratectomy (PRK), Small-Incision Lenticule Extraction (SMILE) and Radial Keratotomy (RK), often experience vision disturbances including glare, halos and starbursts, due to increased optical aberrations and light scatter under low-light (mesopic), low-contrast conditions. These disturbances can significantly impair night driving and daily functioning in dim environments. Phentolamine Ophthalmic Solution 0.75% is designed to reduce pupil diameter through a sympatholytic mechanism of action that avoids engaging the ciliary muscle, potentially reducing risks such as retinal tears or detachment associated with older parasympathomimetic agents.

The LYNX-2 study met its primary endpoint of a gain of three lines (or 15 letters) or more of distance vision improvement on a low contrast chart in low light conditions after 15 days of dosing. In the study, 17.3% of patients treated with Phentolamine Ophthalmic Solution 0.75% achieved a ≥15-letter Early Treatment Diabetic Retinopathy Study (ETDRS) (≥ 3-line) improvement in Mesopic Low Contrast Distance Visual Acuity (mLCVA) at Day 15, compared to 9.2% in the placebo group (p<0.05).

“In LYNX-2, Phentolamine Ophthalmic Solution 0.75% delivered a statistically significant primary endpoint. In addition, patient-reported outcome results demonstrated improvements in night-driving vision, enabling patients to function more effectively in low-light, low-contrast conditions,” said George Magrath, MD, CEO, Opus Genetics. “This data builds on earlier results from the LYNX-1 trial and provides evidence of efficacy for this condition, which currently has no FDA-approved therapies. We believe this therapy could address a true unmet need and could offer meaningful benefits to keratorefractive patients experiencing glare, halos, and reduced functional vision in low-light, low-contrast environments.”

“The positive results from the LYNX-2 trial reinforce the potential of Phentolamine Ophthalmic Solution 0.75% as a first-in-class treatment for keratorefractive patients with vison disturbances under low-light conditions,” said Jay Pepose, MD, PhD, Chief Medical Advisor, Opus Genetics. “After just 15 days of treatment, 17% of patients with dysphotopsia following keratorefractive surgery achieved at least 15-letter gain in mesopic low contrast distance vision. Importantly, we also saw functional improvements in difficulty of seeing the road because of oncoming headlights; and difficulty seeing due to glare when driving at dawn or dusk, as reported by patients in the trial.”

LYNX-2 Phase 3 Study

LYNX-2 was a randomized, double-masked, placebo-controlled Phase 3 trial evaluating the safety and efficacy of Phentolamine Ophthalmic Solution 0.75% in 199 patients who had previously undergone keratorefractive surgery and reported decreased visual acuity under mesopic low contrast conditions, and who were randomized to receive either Phentolamine or placebo, self-administered in both eyes, nightly, treated and observed over 6 weeks. The mITT Population includes all randomized patients who received at least one dose of study medication and was used for the primary endpoint analysis and to analyze efficacy endpoints. The trial was conducted under a Special Protocol Assessment (SPA) agreement with the U.S. FDA.

Top-Line Results:

• The primary endpoint was defined as the percentage of patients achieving a ≥15-letter ETDRS (≥3-line) improvement in mesopic low contrast distance visual acuity (mLCVA).
  
  
• 17.3% of patients in the Phentolamine arm achieved ≥15-letter ETDRS (≥3-line) gain in mLCVA at Day 15, compared to 9.2% of those receiving placebo (p<0.05).
  
  
• Patient-reported benefit was observed at Day 15 in difficulty of seeing the road because of oncoming headlights and difficulty seeing due to glare when driving at dawn or dusk, in patients taking Phentolamine Ophthalmic Solution 0.75% compared to placebo (p<0.05) when assessed by the validated Vision and Night Driving Questionnaire (VND-Q).
  
  

As per the pre-specified testing, no evidence of tachyphylaxis out to Week 6 of dosing.¹

• Phentolamine Ophthalmic Solution 0.75% demonstrated a safety profile consistent with previous trials, with no new safety signal identified.
  
  

LYNX-2 patients will continue to be monitored for long-term safety over 48 weeks. Additional details on the study design can be found at ClinicalTrials.gov (NCT06349759).

Opus Genetics and Viatris (through its affiliate) are parties to a global licensing agreement which provides for the development of Phentolamine Ophthalmic Solution 0.75% and grants exclusive rights to Viatris to commercialize Phentolamine Ophthalmic Solution 0.75% in the U.S.

¹ The study is also designed to examine tachyphylaxis of the therapeutic response to Phentolamine Ophthalmic Solution 0.75% for mLCVA. This was to be achieved by comparing change from Baseline at Week 6 in the Phentolamine Ophthalmic Solution 0.75% group to the best change from baseline achieved during the first month of treatment for mLCVA.

About Phentolamine Ophthalmic Solution 0.75%
Phentolamine Ophthalmic Solution 0.75% is a non-selective alpha-1 and alpha-2 adrenergic antagonist to reduce pupil size. It works by uniquely blocking the alpha-1 receptors found on the radial iris dilator muscles, which are activated by the alpha-1 adrenergic receptors, without affecting the ciliary muscle. Phentolamine Ophthalmic Solution 0.75% is currently being evaluated in two Phase 3 trials programs for the treatment of dim (mesopic) light vision disturbances (sometimes referred to as DLD) after keratorefractive surgery (LYNX clinical program) and presbyopia (VEGA clinical program). The U.S. FDA granted Fast Track designation to Phentolamine Ophthalmic Solution 0.75% for the treatment of significant, chronic night driving impairment with concomitant increased risk of motor vehicle accidents and debilitating loss of best spectacle corrected mesopic vision in keratorefractive patients with photic phenomena (i.e., glare, halos, starburst).

About Opus Genetics

Opus Genetics is a clinical-stage biopharmaceutical company developing gene and small molecule therapies for vision-threatening eye diseases. The company’s pipeline features AAV-based gene therapies targeting inherited retinal diseases such including Leber congenital amaurosis (LCA), bestrophinopathy, and retinitis pigmentosa. Its lead candidate, OPGx-LCA5, is in a Phase 1/2 trial for LCA5-related mutations and has shown encouraging early results. Additional programs include OPGx-BEST1, a gene therapy targeting BEST1-related retinal degeneration and a Phase 3-ready small molecule therapy for diabetic retinopathy, developed under a Special Protocol Agreement with the FDA. Opus is also advancing Phentolamine Ophthalmic Solution 0.75%, a partnered therapy currently approved in one indication and is being studied in two Phase 3 programs for presbyopia and dim light vision disturbances. The company is based in Research Triangle Park, NC. For more information, visit www.opusgtx.com. 

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Contacts
Investors 
Jenny Kobin
Remy Bernarda
IR Advisory Solutions
ir@opusgtx.com

Media
Kimberly Ha
KKH Advisors
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kimberly.ha@kkhadvisors.com

FAQ

What were the main results of Opus Genetics' LYNX-2 Phase 3 trial for Phentolamine?

The trial met its primary endpoint with 17.3% of treated patients achieving ≥15-letter improvement in mesopic low contrast distance visual acuity compared to 9.2% in placebo, showing statistical significance (p<0.05).

How does Phentolamine Ophthalmic Solution 0.75% work for night vision problems?

It reduces pupil diameter through a sympatholytic mechanism of action that avoids engaging the ciliary muscle, potentially reducing risks associated with older treatments.

What is the current regulatory status of Opus Genetics' Phentolamine eye drops?

The drug has received FDA Fast-Track Designation and was studied under a Special Protocol Assessment agreement, with no current FDA-approved therapies for this condition.

What are the safety concerns with Opus Genetics' Phentolamine eye drops?

The drug showed a consistent safety profile with previous trials and no new safety signals, though long-term safety monitoring will continue for 48 weeks.

Who will commercialize Phentolamine Ophthalmic Solution 0.75% in the United States?

Viatris has exclusive rights to commercialize the product in the U.S. through a global licensing agreement with Opus Genetics.