Perfuse Therapeutics Announces Positive Results from Phase 1/2a Trial of PER-001 Intravitreal Implant in Patients with Glaucoma

Perfuse Therapeutics announced positive 24-week results from its completed phase 1/2a trial of PER-001, a first in class endothelin antagonist intravitreal implant for glaucoma.

Steven Mansberger, MD, MPH, Chief of Ophthalmology and Director of Glaucoma Services at Legacy Devers Eye Institute, and an investigator in the study, shared the results in an oral presentation at the Association for Research in Vision and Ophthalmology (ARVO) meeting.

Data from the trial showed a single intravitreal administration of PER-001, added to existing standard-of-care IOP reducing therapies, increased ocular blood flow and improved both visual function and anatomic structure, each of which are registrable outcomes, as measured by visual field (VF) sensitivity and optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness. PER-001 was safe and well-tolerated over the 6-month study period.

“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. We plan to advance the clinical development of PER-001, with initiation of an adaptive phase 2b trial in glaucoma in the second half of 2025 that we believe could serve as one of two pivotal studies required for registration.”

“For decades, glaucoma treatments have focused on lowering intraocular pressure (IOP). Yet, many patients still experience vision loss and progress to blindness,” said Dr. Mansberger. “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, a well-established mediator of vascular dysfunction in the disease. 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.”

PER-001 Phase 1/2a Study Design

The phase 1/2a clinical trial was a multicenter two-part trial designed to assess the safety and tolerability of the PER-001 intravitreal implant in patients with glaucoma. Exploratory objectives included pharmacodynamic (optic nerve head blood flow), functional (VF), and structural (OCT RNFL) effects of PER-001.

The phase 1 part of the trial, a first-in-human, open-label, single ascending dose (SAD) study, assessed the safety and tolerability of two doses of a single PER-001 administration in six patients with advanced glaucoma (n=3 per dose). Phase 2a, a randomized, patient and reading center masked study, evaluated the PER-001 low and high dose against sham control in patients with progressive mild-to-moderate glaucoma (n=approximately 8 for each of the low dose, high dose, and sham control groups). A total of 33 participants were enrolled and received a single intravitreal PER-001 administration or sham injection while continuing their existing pre-study IOP-lowering treatments. Participants were followed for 24 weeks after dosing.

PER-001 Safety Results

For the phase 1/2a study, the 24-week data demonstrated that PER-001 was safe and well-tolerated. There were 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. Additionally, there were no reports of endophthalmitis, intraocular inflammation, uveitis, or retinal vasculitis. There were no changes in IOP therapy, and best-corrected visual acuity was stable during the trial.

PER-001 Exploratory Efficacy Results

• Increased ocular blood flow (Mean Blur Rate). 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 out to Week 24 for both doses combined across Phase 1/2a.
• Improved function (VF). Patients treated with PER-001 showed improved vision; the improvement in VF mean deviation from baseline was +1.5 and +1.1 decibel (dB) per year at 24 weeks for high dose and low dose, respectively, in Phase 2a. In contrast, the sham control group worsened in VF mean deviation of –1.2 dB per year over the same period.
• Improved structure (OCT RNFL). Patients treated with PER-001 showed improved anatomic structure; the increase in RNFL thickness from baseline was +7.7 and +2.4 microns per year for low dose and high dose, respectively, as measured by OCT at 24 weeks in Phase 2a. In contrast, the sham control group had a decrease in RNFL thickness of –6.8 microns per year over the same period.
• There was a strong, linear relationship between the functional (VF) and structural (RNFL) improvements (Pearson Correlation Coefficient = 0.721; p = 0.0003; R² = 0.52).

The presentation, “PER-001, an endothelin antagonist, increased optic nerve head blood flow with structural and functional improvements in patients with glaucoma”, is available under the News section of the company’s website. The abstract can be found on the ARVO website.