Biopharmaceutical company Perfuse Therapeutics has announced positive 24-week results from its completed Phase 1/2a clinical trial of PER-001, a first-in-class endothelin antagonist intravitreal implant for glaucoma. The data, presented at the Association for Research in Vision and Ophthalmology (ARVO) meeting, suggests PER-001 could become the first disease-modifying treatment for glaucoma, the leading cause of irreversible global blindness.
The multi-center trial demonstrated that a single intravitreal administration of PER-001, when added to existing standard-of-care intraocular pressure (IOP) reducing therapies, increased ocular blood flow and improved both visual function and anatomic structure in patients with glaucoma.
"Our mission is to develop the first disease-modifying treatment for glaucoma, the leading cause of irreversible global blindness with no approved therapies," said Sevgi Gurkan, MD, CEO and Founder of Perfuse Therapeutics. "These data are very promising, with PER-001 improving vision in glaucoma patients."
Trial Design and Patient Population
The Phase 1/2a clinical trial consisted of two parts. The Phase 1 portion was a first-in-human, open-label, single ascending dose study that assessed the safety and tolerability of two doses in six patients with advanced glaucoma. The Phase 2a component was a randomized, patient and reading center masked study that evaluated PER-001 low and high doses against sham control in patients with progressive mild-to-moderate glaucoma.
A total of 33 participants were enrolled across both portions of the study and followed for 24 weeks after receiving either PER-001 or a sham injection while continuing their existing pre-study IOP-lowering treatments.
Significant Improvements in Visual Function and Structure
The trial demonstrated remarkable improvements in both functional and structural outcomes:
Visual Field Improvements: Patients treated with PER-001 showed improved vision with visual field mean deviation from baseline of +1.5 and +1.1 decibel (dB) per year at 24 weeks for high dose and low dose, respectively. In contrast, the sham control group worsened by -1.2 dB per year.
Structural Improvements: The increase in retinal nerve fiber layer (RNFL) thickness from baseline was +7.7 and +2.4 microns per year for low dose and high dose, respectively, as measured by optical coherence tomography (OCT) at 24 weeks. The sham control group showed a decrease of -6.8 microns per year.
Notably, researchers observed a strong, linear relationship between the functional and structural improvements (Pearson Correlation Coefficient = 0.721; p = 0.0003; R² = 0.52).
Mechanism of Action and Blood Flow Improvements
PER-001 works by targeting the endothelin pathway, a well-established mediator of vascular dysfunction in glaucoma. Endothelin is the most potent vasoconstrictor in the human body and is upregulated in glaucoma.
For patients treated with PER-001, a clinically meaningful increase in optic nerve head blood flow from baseline was observed starting at Week 1 and was sustained through Week 24 for both doses. This validates the target engagement and the sustained release profile of PER-001, which enables a convenient six-month dosing frequency.
Safety and Tolerability Profile
The 24-week data demonstrated that PER-001 was safe and well-tolerated. There were only two drug-related adverse events of vitreous floaters, both of which were mild, intermittent, and self-resolved. No other drug-related adverse events or serious adverse events were reported.
Importantly, there were no reports of endophthalmitis, intraocular inflammation, uveitis, or retinal vasculitis. There were no changes in IOP therapy, and best-corrected visual acuity remained stable during the trial.
Expert Commentary
"For decades, glaucoma treatments have focused on lowering intraocular pressure. Yet, many patients still experience vision loss and progress to blindness," said Dr. Steven Mansberger, Chief of Ophthalmology and Director of Glaucoma Services at Legacy Devers Eye Institute, and an investigator in the study.
"What is particularly remarkable is that treatment with PER-001 led to improvements in ocular blood flow, optic nerve structure, and visual function. These findings suggest a potentially transformative approach for the treatment of glaucoma by targeting the endothelin pathway. Notably, this represents the first time endothelin antagonism has been studied in the human eye, marking the potential start of an exciting new era of treatment for patients with glaucoma."
Future Development Plans
Based on these promising results, Perfuse Therapeutics plans to advance the clinical development of PER-001, with initiation of an adaptive Phase 2b trial in glaucoma in the second half of 2025. The company believes this trial could serve as one of two pivotal studies required for registration.
Glaucoma: A Growing Public Health Challenge
In the United States, approximately four million people are diagnosed with glaucoma, and its prevalence is projected to double within the next 15 years. Despite the availability of pharmacological, laser, and surgical treatments to lower IOP, there are no FDA-approved therapies specifically for glaucoma, and many patients continue to experience vision loss even with effective IOP-lowering treatments.
The development of PER-001 represents a novel approach to glaucoma treatment that goes beyond traditional IOP-lowering strategies to address the underlying vascular dysfunction and potentially modify the disease course, offering new hope for patients with this sight-threatening condition.
