Genentech announced encouraging results from the phase 2 BOULEVARD study. In people with vision loss from diabetic macular edema (DME), treatment with intravitreal RG7716 demonstrated clinically meaningful visual acuity gains from baseline, and statistically significant improvements in visual acuity compared with ranibizumab, according to Genetech.
Key secondary and exploratory anatomical outcomes – reduction of central retina thickness and improvements in diabetic retinopathy severity scores – were supportive of the primary outcome.
RG7716 is the first bispecific, monoclonal antibody specifically designed for the eye that simultaneously binds to and inactivates vascular endothelial growth factor A (VEGF-A) and Angiopoietin-2 (Ang-2), according to Genentech. These data were presented at Angiogenesis, Exudation, and Degeneration 2018, a medical symposium presented by Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine, part of the University of Miami Health System.
“For the first time in diabetic macular edema, a clinically meaningful and statistically significant improvement in visual acuity compared to anti-VEGF alone has been demonstrated by simultaneously neutralizing both Angiopoietin-2 and VEGF-A with a bispecific antibody,” Sandra Horning, M.D., chief medical officer and head of Global Product Development, said in a company news release. “These phase 2 results show the potential of RG7716 for people living with diabetic macular edema, a leading cause of vision loss in working-age adults. There remains a significant unmet medical need for more efficacious and longer lasting therapies for diabetic macular edema.”
BOULEVARD assessed two doses of RG7716 (1.5 mg and 6 mg) versus ranibizumab standard of care (0.3 mg) given as monthly intravitreal injections. The study met its primary endpoint, demonstrating a significant improvement in adjusted best corrected visual acuity (BCVA) at week 24 for RG7716 versus ranibizumab in treatment-naïve patients: 6 mg RG7716 resulted in an adjusted mean improvement of 13.9 chart letters from baseline, compared to 11.7 letters in patients treated with 1.5 mg RG7716, and 10.3 letters in patients treated with 0.3 mg ranibizumab. The difference between 6 mg RG7716 and 0.3 mg ranibizumab was statistically significant with an adjusted mean difference of +3.6 letters (P = 0.03, 80% CI 1.53-5.61, prespecified significance level: P < 0.2).
Secondary endpoints of the study included assessment of functional and anatomic measures versus ranibizumab standard of care. Both RG7716 arms achieved higher proportions of patients gaining more than two, and more than three, lines of visual acuity. Both RG7716 arms resulted in greater reduction of central retina thickness as well as a greater two-step improvement of diabetic retinopathy severity. RG7716 was well tolerated with no new safety signals observed. Additional data analyses of BOULEVARD are ongoing and will be presented at future medical meetings.
In addition to BOULEVARD, RG7716 is also being evaluated in the phase 2 AVENUE and STAIRWAY studies in neovascular age-related macular degeneration (AMD), also known as wet AMD. All three studies have finished enrollment and are currently in follow-up. Genentech is committed to presenting data from all phase 2 studies at upcoming medical meetings, and we plan to discuss our phase 3 program with the FDA following data assessment.
About the BOULEVARD Study
BOULEVARD (NCT02699450 is a phase 2 study designed to assess the efficacy and safety of RG7716 compared with ranibizumab in people with diabetic macular edema (DME). This prospective, randomized, comparator-controlled, double-masked, multicenter, multi-dose, three-arm study enrolled 229 participants in more than 90 sites across the United States. All patients were dosed monthly (28 days +/– 7 days) for 20 weeks. Subsequently, there is an observation period of up to 16 weeks for a total study length of 36 weeks. The primary objective of BOULEVARD was to demonstrate superior gains in visual acuity compared to ranibizumab injections at week 24 in anti-vascular endothelial growth factor (VEGF) treatment-naïve participants.