Nesvategrast for Diabetic Retinopathy Misses Primary Endpoint in Phase 2 Trial

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Topline data from the phase 2 DR:EAM trial of nesvategrast (OTT166), a novel eye drop for diabetic retinopathy, revealed the study did not achieve its primary or key secondary efficacy end points, despite demonstrating strong safety and tolerability.¹

Announced by OcuTerra on March 14, 2024, the study failed to exhibit a statistically significant improvement on the diabetic retinopathy severity scale (DRSS) among patients with diabetic retinopathy treated with nesvategrast, compared with a placebo-treated cohort.

“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 of progression of diabetic retinopathy, stated Kerrie Brady, chief executive officer and president of OcuTerra. “We plan to review the full dataset from the DR:EAM study to evaluate the future of the nesvategrast program.”

An investigational, novel, selective small molecule RGD integrin inhibitor, nesvategrast was designed to have an optimum balance of physiochemical properties for distribution in the retina in high concentrations with topical administration to the eye.

The phase 2, multicenter, randomized, double-masked DR:EAM clinical trial was intended to evaluate the safety and efficacy of a daily topical administration of high- and low-dose nesvategrast versus placebo for 24 weeks.² The study population consisted of 225 adult patients with moderately severe to severe non-proliferative diabetic retinopathy (NPDR) or mild proliferative diabetic retinopathy (PDR) with minimal vision loss.

Its primary efficacy endpoint was the percentage of patients experiencing a ≥2-step improvement in the DRSS, with additional endpoints ranging from the prevention of progression to vision-threatening events to the amount of delayed time to intravitreal injection or laser treatment.

According to the topline data, nesvategrast treatment was both safe and well-tolerated. Alongside failing to improve the DRSS in the primary efficacy endpoint, nesvategrast also demonstrated no significant impact on the progression of the disease, as measured by DRSS, in a key secondary endpoint.

Further analysis of a key secondary end point, the development of vision-threatening events stratified by baseline disease severity, revealed a statistically significant improvement in patients with moderately severe and severe NPDR at baseline for preventing VTEs by week 24 (P = .045).

Diabetic retinopathy is the leading cause of vision loss and blindness among working-age adults in the United States, affecting nearly 10 million people.³ Current standard of care is active surveillance until the onset of a sight-threatening condition, after which patients receive intravitreal injections or laser to prevent the growth of new blood vessels and decrease fluid build-up.

Despite missing the primary efficacy end point for nesvategrast, Ocuterra expressed its intention to evaluate strategic alternatives and plans to share more details in the future

“While our phase 2 topline data did not show the efficacy we had hoped, we had advanced the program with substantial preclinical and clinical data and will use learnings to help inform the ophthalmic community and their future work,” stated David Tanzer, MD, chief medical officer or OcuTerra.

References

1. _{OCUTERRA announces topline data from phase 2 DR:EAM trial evaluating nesvategrast (ott166 5%) for patients with diabetic retinopathy. Business Wire. March 14, 2024. Accessed March 14, 2024. https://www.businesswire.com/news/home/20240314840296/en/OcuTerra-Announces-Topline-Data-from-Phase-2-DREAM-Trial-Evaluating-Nesvategrast-OTT166-5-for-Patients-with-Diabetic-Retinopathy.}
2. _{Ocuterra Therapeutics announces last patient completes final visit in nesvategrast (OTT166) eye drop phase 2 DR:EAM clinical trial in diabetic retinopathy. Business Wire. January 3, 2024. Accessed March 14, 2024. https://www.businesswire.com/news/home/20240103754817/en/OcuTerra-Therapeutics-Announces-Last-Patient-Completes-Final-Visit-in-Nesvategrast-OTT166-Eye-Drop-Phase-2-DREAM-Clinical-Trial-in-Diabetic-Retinopathy.}
3. _{Lundeen EA, Burke-Conte Z, Rein DB, et al. Prevalence of Diabetic Retinopathy in the US in 2021. JAMA Ophthalmol. 2023;141(8):747–754. doi:10.1001/jamaophthalmol.2023.2289}