OcuTerra Therapeutics has announced that its Phase 2 DR:EAM clinical trial of nesvategrast (OTT166) eye drops for diabetic retinopathy (DR) did not meet its primary or key secondary efficacy endpoints. The multicenter, randomized, double-masked study involved 225 adults with moderate to severe non-proliferative DR (NPDR) or mild proliferative DR (PDR) with minimal vision loss.
The trial evaluated the safety and efficacy of high and low doses of daily topical administration of nesvategrast compared to placebo over 24 weeks. The primary efficacy endpoint was the percentage of subjects achieving a two-step or greater improvement on the DR Severity Scale (DRSS).
Trial Details and Results
The DR:EAM trial (NCT05409235) aimed to assess whether nesvategrast could improve DRSS scores and prevent the progression of diabetic retinopathy. Additional objectives included evaluating the prevention of progression to vision-threatening events, the delay in needing intravitreal injections or laser treatment, and exploratory imaging endpoints.
Topline data indicated that nesvategrast did not demonstrate a statistically significant improvement in DRSS scores compared to the placebo group. The treatment also failed to significantly impact the progression of the disease as measured by DRSS.
Sub-analysis Provides Hope
Despite the overall negative results, a sub-analysis revealed a statistically significant benefit in preventing the onset of vision-threatening events by week 24 in patients with moderately severe to severe NPDR at baseline (p=0.045).
Company Response
OcuTerra CEO and president Kerrie Brady stated, "We are disappointed that the topline data on nesvategrast from our Phase 2 DR:EAM clinical trial did not demonstrate a statistically significant impact on severity or progression of diabetic retinopathy." The company plans to review the full dataset from the DR:EAM study to evaluate the future of the nesvategrast program.
About Nesvategrast
Nesvategrast (OTT166) is a selective RGD integrin inhibitor designed as an eye drop for patients with diabetic retinopathy (DR). It is designed to have an optimum balance of physiochemical properties to allow it to distribute to the retina in high concentrations after topical (eye drop) administration to the eye. In preclinical studies, nesvategrast selectively inhibited key RGD integrin subtypes, including αvβ3, to regulate cellular responses to VEGF and other growth factors known to contribute to development and progression of diabetic retinopathy and other ocular diseases.
Diabetic Retinopathy: A Significant Unmet Need
Diabetic retinopathy is the most common diabetic eye disease and a leading cause of vision loss and blindness in working-age adults. It affects nearly 10 million people in the US. The current standard of care often involves a "watch-and-wait" approach until sight-threatening complications arise, necessitating intravitreal injections or laser treatments.
