EyePoint Pharmaceuticals announces first patient dosed in global Phase 3 LUGANO clinical trial of Duravyu for wet AMD

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EyePoint Pharmaceuticals Inc. has does the first patient in the Phase 3 LUGANO clinical trial of Duravyu, formerly EYP-1901, for the treatment of wet age-related macular degeneration (wet AMD).

According to the company, Duravyu is an investigational sustained delivery therapy delivering patent-protected vorolanib, a selective tyrosine kinase inhibitor formulated in proprietary bioerodible Durasert E.

Jay S. Duker, MD, president and CEO of EyePoint, noted the dosing of the first patient in the global Phase 3 LUGANO trial represents a significant milestone for the company and Duravyu, underscoring its leadership in sustained-release ocular drug delivery and commitment to developing innovative therapies for patients with serious retinal diseases.

“Our Phase 3 LUGANO and LUCIA trials were designed for potential global regulatory and commercial success based on our alignment with the FDA, as they follow a proven non-inferiority approval pathway.,” he said in the news release. “We have entered Phase 3 leveraging learnings from our robust DAVIO and DAVIO 2 clinical trials to facilitate accelerated enrollment so that wet AMD patients may receive this potentially paradigm-shifting treatment as fast as possible.”

Ramiro Ribeiro, MD, PhD, chief medical officer of EyePoint, pointed out that there are more than

150 clinical trial sites already committed, which he said makes the company well positioned to rapidly enroll patients globally in the pivotal LUGANO trial, with the LUCIA trial to quickly follow.

“We are encouraged by the exceptional patient and investigator enthusiasm for our Phase 3 protocol, which aligns with clinical practice by including active treatment through trial duration,” he said. “Patients will receive Duravyu every 6 months or on-label aflibercept every two months, beginning after three loading doses of aflibercept with randomization occurring on Day 1. Further, the trials include both treatment-naïve and treatment experienced patients, which we believe more accurately represent the real-world patient population and increases our probability of success based on the positive DAVIO 2 data. We are optimistic that Duravyu has the potential to change the current treatment paradigm and revolutionize clinical outcomes for patients suffering from serious retinal diseases.”

Carl Regillo, MD, FACS, director of Retina Service at Wills Eye Hospital and Professor of Ophthalmology at Thomas Jefferson University, pointed out the investigational sustained delivery therapy could fill an unmet need for wet AMD patients.

“Wet AMD patients face significant unmet need for a safe and efficacious sustained delivery treatment, as the current standard of care requires frequent injections resulting in a high treatment burden and, ultimately, delayed or missed appointments that potentially leave patients with no active drug to prevent disease progression and associated vision loss,” Regillo said in the news release. “Based on the promising clinical data generated in the DAVIO and DAVIO 2 trials, as well as the favorable safety profile from over 190 patients treated, I believe DURAVYU has the potential to improve the treatment paradigm for this lifelong disease by maintaining a majority of patients with active disease with no supplemental anti-VEGF therapy for six months or longer. The pivotal trials of DURAVYU in wet AMD represent an exciting milestone for patients, caregivers and physicians as we work to improve quality of life and patient vision.”

Ashkan M. Abbey, M.D., a principal investigator in the LUGANO clinical trial and director of Clinical Research at Texas Retina Associates, pointed out in the news release that despite new treatments entering the wet AMD market, there remains a need for safe and durable treatments that provide sustained treatment while decreasing the patient’s need for frequent injections.

“Duravyu brings a new mechanism of action with the potential to treat wet AMD patients every six months or longer to actively safeguard patients’ vision between visits. We are proud to be the first site to treat a patient in the LUGANO clinical trial, and we look forward to continuing to collaborate with EyePoint to rapidly enroll patients.”

The company noted its LUGANO and LUCIA trials are global, randomized, double-masked, Phase 3 studies comparing Duravyu to aflibercept, designed to assess the efficacy and safety of Duravyu in patients with active wet AMD, including both previously treated and treatment-naïve individuals. Each trial aims to enroll approximately 400 patients worldwide, who will be randomly assigned to receive either a 2.7 mg dose of Duravyu or an on-label dose of aflibercept. These are the only Phase 3 pivotal trials for sustained-release wet AMD that evaluate re-dosing in both trials.

Patients in the Duravyu treatment group will receive an intravitreal injection every six months, beginning in the second month of the trial. The delivery of Duravyu follows the same procedure as FDA-approved anti-VEGF treatments, using a standard intravitreal injection in a physician's office. The primary endpoint of these Phase 3 trials is the average change in best corrected visual acuity (BCVA) at weeks 52 and 56 compared to baseline. Secondary endpoints include safety, reduction in treatment burden, the percentage of eyes free of additional aflibercept injections, and anatomical outcomes measured by optical coherence tomography (OCT).

Duravyu, previously known as EYP-1901, is being developed as a potentially groundbreaking treatment for VEGF-mediated retinal diseases. It delivers vorolanib, a potent, selective, patent-protected tyrosine kinase inhibitor (TKI), through EyePoint’s proprietary sustained-release Durasert E technology. Vorolanib offers a novel mechanism for treating VEGF-mediated retinal diseases as a pan-VEGF receptor inhibitor, targeting all VEGF receptors. Additionally, vorolanib has shown neuroprotective properties in an in-vivo model of retinal detachment and may have antifibrotic benefits by blocking PDGF. Duravyu is shipped and stored at room temperature and is administered via a standard intravitreal injection. It becomes bioavailable immediately and releases the drug with zero-order kinetics for up to nine months.

According to the company, positive data from the Phase 1 DAVIO and Phase 2 DAVIO 2 trials demonstrated clinically meaningful outcomes in wet AMD, including stable visual acuity, central subfield thickness (CST), and a favorable safety profile. In DAVIO 2, Duravyu reduced treatment burden by approximately 88% at eight months—six months after treatment—with over 80% of patients either supplement-free or requiring just one supplemental anti-VEGF injection through the eight-month period.

These findings supported the progression of Duravyu's wet AMD program and led to the initiation of the Phase 3 LUGANO trial, with the LUCIA trial set to begin by the end of 2024, the company noted.

Duravyu is also being studied in the Phase 2 VERONA trial for diabetic macular edema (DME), with topline data expected in the first quarter of 2025.