OcuTerra Therapeutics, Inc. released topline data from its phase 2 Diabetic Retinopathy: Early Active Management (DR:EAM) study evaluating nesvategrast (OTT166 5%), a novel, selective RGD integrin inhibitor.
Let’s start with OcuTerra.
Headquartered in Boston, Massachusetts, OcuTerra is a clinical-stage biotechnology company developing therapeutics for ophthalmic diseases with no current preventative or progression-managed treatments.
Its initial therapeutic: OTI66 for diabetic retinopathy (DR).
Why DR?
According to the Centers for Disease Control and Prevention (CDC), an estimated 9.6 million individuals in the U.S. had DR in 2021; of that, 1.84 million were diagnosed with vision-threatening DR.
In fact, the global prevalence of DR was reported among an estimated 103 million individuals in 2020, with that number expected to increase to 130 million in 2030 and 161 million in 2045.
And the current standard of care?
At present, eyecare professionals (ECPs) have adopted the “wait-and-watch” approach among patients with nonproliferative DR (NPDR) until a vision-threatening complication arises.
From there, intravitreal anti-vascular endothelial growth factor (VEGF) injections or panretinal laser photocoagulation have become just a few of the standard forms of treatment.
How does this compare to OTT166?
First and foremost: This therapeutic is formulated as a topical compound (ie: an eye drop)—a stark contrast to the current invasive methods of treatment.
Secondly: The drop is intended to be administered at home, by the patient, at the earliest signs of DR.
Give me the rundown on it.
OTT166 is a novel, patented, potent, and selective small-molecule arginine-glycine-aspartic acid (RGD)-tripeptide integrin inhibitor.
How it works: by regulating cellular responses to VEGF, among other growth factors, OTT166 may help to inhibit the following that are part of the development/progression of DR and other ocular diseases:
- Angiogenesis
- Vascular leakage
- Fibrosis
- Inflammation
The goal: OTT166 is intended to non-invasively reach the retina in order to prevent or slow DR progression.
Sounds like a game-changer. Now talk about this phase 2 study.
The multicenter, randomized, double-masked, vehicle-controlled phase 2 DR:EAM study (NCT05409235) enrolled 225 patients (aged 18+) with moderately-severe to severe NPDR and who were treatment naïve. See here for patient inclusion/exclusion criteria.
Participants were randomized into four cohorts:
- Cohort 1 (OTT166)
- Low dose administered for 24 weeks
- Cohort 2 (OTT166)
- High dose administered for 24 weeks
- Cohort 1 (vehicle control )
- Vehicle control (placebo) administered for 24 weeks
- Cohort 2 (vehicle control)
- Vehicle control (placebo) administered for 24 weeks
And the outcome measures?
Primary outcome measures included:
- Participants with treatment-emergent adverse events (TEAEs) up to Week 24 (evaluating safety of OTT166 5%)
- Participants who improved by ≥ 2 steps from baseline in Diabetic Retinopathy Severity Scale (DRSS) scores at Week 24
See here for secondary outcome measures.
Now these findings.
The good: OTT166 was found to be safe and well tolerated, meeting its primary safety endpoint.
The bad: The study did not meet its primary or key secondary efficacy endpoints.
Give me details on this bad news.
Per OcuTerra, the study failed to demonstrate a statistically significant improvement on the DRSS for either cohort of the OTT166-treated patients vs the placebo group (which was the primary efficacy endpoint).
Further, the data showed that OTT166 did not have “statistically significant impact on severity or progression of [DR],” which was a key secondary endpoint.
Now let’s circle back to the good.
Analysis of the development of vision-threatening events (VTEs) stratified by the level of disease severity at baseline—also a secondary endpoint—was reported to demonstrate “statistically significant improvement in patients with DRSS level 47 and 53 … at baseline in preventing the onset of VTEs by week 24 (p = 0.045).
Note: DRSS level 47 represents moderately severe NPDR, while DRSS level 53 represents severe NPDR.
What did the company have to say about this data?
OcuTerra Chief Medical Officer David Tanzer, MD, noted that, while the phase 2 data did not show the efficacy that the company had hoped for, “We had advanced the program with substantial preclinical and clinical data and will use [those] learnings to help inform the ophthalmic community and their future work.”
And next steps?
Kerrie Brady, OcuTerra’s CEO and president, stated that the company plans to review the full dataset from the DR:EAM study “to evaluate the future of the nesvategrast (OTT166 5%) program.”