FDA warns EyePoint over manufacturing issues with eye implant

EyePoint Pharmaceuticals has encountered further complications with the FDA regarding its operations. The pharmaceutical company, which focuses on ophthalmology, received an FDA warning letter in July at its Watertown, Massachusetts facility. This more severe reprimand follows a Form 483 that EyePoint addressed on March 7. The FDA's citations, discovered during a February inspection, highlighted several issues including batch inconsistencies and inadequate written procedures.

The core of the FDA’s concerns revolves around Yutiq, an implant developed by EyePoint containing the corticosteroid fluocinolone acetonide. This drug-device combination, approved in the U.S. in 2018, was partially sold to Alimera Sciences in an $82.5 million deal. EyePoint has assured that these issues are confined to Yutiq’s manufacturing and should not impact other products in development, such as their leading candidate, Duravyu.

An EyePoint spokesperson stated that the company is fully committed to resolving all FDA observations by implementing corrective actions and process improvements. The first issue highlighted by the FDA involved EyePoint’s inability to eliminate production inconsistencies. Particularly, a specific Yutiq batch exhibited an unusually high release rate for drug cores during testing, which EyePoint failed to adequately investigate.

Additionally, EyePoint’s own investigations did not adequately address the manufacturing issues. The FDA report cited three roof leaks that allowed moisture into controlled manufacturing areas, an issue originating from July 2023. EyePoint indicated plans to collaborate with the building’s owner to evaluate the roof but failed to initiate regular facility inspections to maintain proper manufacturing conditions.

The FDA also criticized EyePoint’s written procedures at the Watertown plant. It pointed out that performance studies for Yutiq did not scientifically prove blend uniformity in the final product. The agency also noted that EyePoint’s operations and engineering teams had not created statistical process control charts to monitor manufacturing performance effectively. The charts generated during the FDA inspection revealed four adverse trends that EyePoint had not previously recognized but required investigation.

Moreover, the FDA took issue with EyePoint’s visual inspection processes during production, stating that the company’s methods lacked action levels for significant defects, which necessitated further investigation.

This regulatory setback follows another challenge for EyePoint earlier this year when its primary pipeline asset, Duravyu, failed to show significant improvement in patient scores on the Diabetic Retinopathy Severity Scale. This disappointing outcome came from the phase 2 PAVIA study in patients with non-proliferative diabetic retinopathy. At that time, Mizuho analyst Graig Suvannavejh described the result as a significant letdown for EyePoint, anticipating questions regarding Duravyu’s potential in treating diabetic macular edema and wet age-related macular degeneration (AMD).

Duravyu is an intravitreal, sustained-release insert that administers the VEGFR/PDGFR tyrosine kinase inhibitor vorolanib to the eye. EyePoint licensed vorolanib from Equinox Science in early 2020.

Despite these setbacks, Mizuho’s Suvannavejh remained somewhat optimistic about EyePoint’s future by mid-August. He noted that his analyst team retains enthusiasm for EyePoint, particularly due to Duravyu's potential in wet AMD, where it could establish itself as a standard of care. EyePoint emphasized during its second-quarter earnings call that moving forward with Duravyu’s phase 3 study in wet AMD remains a top priority.