Phase 3 Failure and Market's Harsh Reaction

EyePoint Pharmaceuticals (EYPT) announced that its Phase 3 LUGANO trial of DURAVIU (vorolanib), a treatment for wet age-related macular degeneration (wet AMD), failed to meet its primary endpoint. The drug failed to demonstrate non-inferiority to aflibercept (brand name Eylea) in terms of visual acuity improvement. As a result, EyePoint's stock price plummeted approximately 70% on the day of the announcement. This represents a significant setback to the company's commercialization plans, which aimed to challenge the market dominance of Eylea as a long-acting drug.

Exploring Approval Possibilities Through Asymmetric Cohort Analysis

The company attributed the failure of the clinical trial to an asymmetric cohort phenomenon, in which approximately 4% of patients in the treatment group, or 9 patients, experienced a significant loss of vision (15 letters or more) unrelated to the disease. In a post-hoc analysis excluding these 9 patients, the drug demonstrated non-inferiority to aflibercept and showed significant efficacy (nominal p-value = 0.0096). Whether the FDA, the regulatory agency, will accept this post-hoc analysis data as reliable evidence of therapeutic effect will be a key issue in the future approval review.

Improved Convenience and Hope for Secondary Endpoint

Although it failed to achieve the primary goal, DURAVIU demonstrated strong advantages in reducing the treatment burden on patients. Clinical results showed a 42% reduction in treatment burden (nominal p-value < 0.0001) compared to the control group, with patients receiving an average of 2 fewer injections during the approximately 56-week clinical period. In addition, 54% of patients maintained their vision for 56 weeks with DURAVIU monotherapy without additional supplemental injections, suggesting that it could be a positive alternative for patients suffering from frequent intraocular injections.

Collaboration and Licensing Agreement with Betta Pharmaceuticals

In 2020, EyePoint acquired global rights (excluding Greater China) to DURAVIU from Equinox Sciences (an affiliate of Betta Pharmaceuticals) for an upfront payment of $1 million USD, plus additional milestone payments and royalties. In 2022, the company entered into an expanded licensing agreement with Betta Pharmaceuticals, granting them exclusive commercialization rights in Greater China, further strengthening the partnership. The failure of this Phase 3 trial, which was intended to establish a foothold in the global market, will negatively impact future milestone payments and commercialization strategies between the two companies.

Next Clinical Trial Results and Future Regulatory Timeline

All eyes are now on the results of the second Phase 3 trial, LUCIA, which is being conducted with the same design. The company plans to announce topline data from the LUCIA trial in the fourth quarter of 2026 and submit a New Drug Application (NDA) to the FDA in the first half of 2027. To regain investor confidence and obtain approval, it will be necessary to address the shortcomings of the LUGANO trial and obtain definitive non-inferiority data in the LUCIA trial.