Article

Positive Phase 2 Bispecific Antibody Data Presented

RG7716 meets primary endpoint in BOULEVARD Phase 2 DME trial.

Dr. Pravin U. Dugel, managing partner of Retinal Consultants of Arizona and clinical professor at the Roski Eye Institute, USC Keck School of Medicine, presented the results of the phase 2 BOULEVARD trial at the Angiogenesis, Exudation, and Degeneration conference in Miami, Florida, on February 10, 2018. The trial tested the efficacy and safety of RG7716 (Hoffman-La Roche), the first anti-VEGF-A/Antiangiopoietin-2 (Ang-2) bispecific antibody designed for intravitreal use in patients with DME.

Dr. Dugel explained, “Targeting additional pathways beyond VEGF could improve BCVA outcomes and decrease treatment burden. Evidence supports rationale for Ang-2 inhibition. Ang-2 has been shown to be elevated in the vitreous of patients with DR and contributes to retinal microvascular inflammation, blood retinal-barrier breakdown, capillary sprouting, and remodeling.”

The BOULEVARD trial met its primary endpoint, as RG7716 demonstrated statistically significant BCVA gains over ranibizumab at week 24 in anti-VEGF treatment-naïve patients with DME. Of the 229 patients with center-involving DME who were enrolled in the study, 168 were treatment naïve. When factored into a linear model adjusting for baseline BCVA and randomization factors, the 6.0-mg RG7716 group gained a mean of 13.9 letters from baseline, which was an improvement of 3.6 letters over the 10.3 letters gained by the 0.3-mg ranibizumab group (P=.03). According to Dr. Dugel, “Ranibizumab performed as expected, with an improvement of visual acuity up to week 16, and a plateau effect thereafter. RG7716 had a dose-dependent response. There was no plateau effect at all.

There was a linear relationship that continued to improve over time, suggesting that a second mechanism of action may be at play, namely Ang-2 inhibition.” The secondary functional and anatomic endpoints supported the BCVA primary outcome. The 6.0-mg RG7716 group had a mean CST reduction of 226 µm compared to 205 µm in the ranibizumab group. Thirty-nine percent of patients in the 6.0-mg RG7716 group had a ≥2 step improvement in Diabetic Retinopathy Severity Score, compared to 12% in the ranibizumab group. The safety profile of RG7716 was comparable to other anti-VEGF drugs, with no new safety signals observed.