RG7716 improves visual acuity in subjects with Diabetic Macular Edema in a Phase 2 study

(c)Pharmacodia.com

Genentech announced results from the Phase II BOULEVARD study, which is evaluating subjects with vision loss from diabetic macular edema (DME), where treatment with intravitreal RG7716 was observed to be clinically meaningful and statistically significant in improvement of visual acuity gains compared with ranibizumab alone.

RG7716 is the first bispecific, monoclonal antibody specifically designed for the eye that simultaneously binds to and neutralizes both Angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A) with high potency and specificity. In diabetic macular edema (DME), Ang-2 works synergistically with VEGF to drive biological pathways that cause vessel permeability and inflammation. Both of these contribute to vascular instability which results in vision loss. Therefore, simultaneous inhibition of both Ang-2 and VEGF may lead to improved outcomes, reduced treatment burden, or both.

Key secondary and exploratory anatomical outcomes – reduction of central retina thickness and improvements in diabetic retinopathy severity scores – were supportive of the primary outcome. 

(c) Community Eye Health Journal

BOULEVARD (NCT02699450) is a Phase II study designed to assess the efficacy and safety of RG7716 (two doses - 1.5 mg and 6 mg) compared with ranibizumab standard of care (0.3 mg) given as monthly intravitreal injections, 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-VEGF treatment-naïve participants.

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, pre-specified 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 II AVENUE and STAIRWAY studies in neovascular age-related macular degeneration (nAMD). All three studies have finished enrollment and are currently in follow-up.

---

More about Retina Global here. We seek your support. Click here to donate.