Additional analyses of the phase 2 BOULEVARD trial, which found faricimab not only led to improved best-corrected visual acuity and central subfield thickness from baseline, but also provided anatomical benefits and displayed a potential for extended durability compared to anti-VEGF monotherapy, were presented during ASRS 2019
An analysis of the phase 2 BOULEVARD trial presented at the 2019 American Society of Retina Specialists Annual Meeting highlighted the anatomical benefits and the potential for extended durability with faricimab compared with anti-VEGF mono therapy in patients with diabetic macular edema (DME).
Data from the analyses, which was presented for the first time at ESRS 2019 by Vrinda Hershberger, MD, PhD, found that faricimab not only led to improved best-corrected visual acuity and central subfield thickness from baseline, but also provided anatomical benefits and displayed a potential for extended durability compared to anti-VEGF monotherapy.
In between sessions, Hershberger, vitreal retina surgeon with Florida Eye Associates, sat down with MD Magazine at ESRS 2019 to discuss the findings of the analysis and what they mean going forward.
MD Mag: What were the results of the BOULEVARD trial and how will faricimab impact clinical care?
Hershberger: Until now, starting in about 2004, 3 molecules to treat most neovascular diseases or vascular diseases — such as (bevacizumab), aflibercept, and ranibizumab and all three of them work exactly by the same mechanism faction, which is inhibition of pressure. As we know from 15 years of clinical trials, we have a ceiling effect with these drugs that really is not that different. There might be some small differences as seen in the CATT and IVAN trial and other trials, but what we know about these diseases also is that they're multifactorial, multi-mechanistic diseases and we are only attacking one mechanism of action with the anti-VEGF drugs.
Faricimab is the first, novel bispecific antibody designed by Roche. This molecule has two FAB arms — one binds VEGF-A, the other binds Ang-2. Ang-2, we know now, is a modulator of angiogenesis and it acts as a body by inhibiting Ang-1. Think of Ang-1 as a good guy, it protects vascular homeostasis maintains stable cellular vasculature. Ang-2 is upregulated in CRVO, DME, AMD and it inhibits the effect the protective effect of Ang-1 by blocking TIE-2 — the tyrosine kinase receptor. So, now this increases self-permeability, destabilization. It also upregulates VEGF-A. Now, we know that VEGF-A promotes the sprouting of new blood vessels and endothelial destabilization.
So, coming back to faricimab. You have a molecule with one arm blocking Ang-2, the other arm blocking VEGF-A, and a very unique FC receptor of FC function that does not have any effect or function but increases systemic clearance by which decreasing the inflammatory potential of the molecule. What's also unique about it is that it can bind either VEGF-A or Ang-2 without steric hindrance of one of the arms blocking the other arms ability to bind the molecule and it does so with very high specificity and potency. This molecule has shown very good results in the phase 1 and the phase 2 studies in BOULEVARD.
Faricimab treated patients showed a statistically significant gain over 0.3 milligram ranibizumab. What is even more interesting is in the off treatment portion of the study the patients were treated every 4 weeks up to week 20, starting week 24 they were observed every 4 weeks up to week 36 with treatment allowed if they met pre-specified disease criteria of lack of durability, which means if the patient lost more than 5 letters of vision or gained more than 50 microns of central subfield thickness. In the off treatment phase the 0.6 milligram arm and the 1.5 milligram arm showed increase durability ,both, in the previously treated patients and the treatment naive patients — showing a durability effect of a significant proportion of more patients requiring less rescue in both those arms.
That is something unique. I mean, we have a lot of approaches right now to the dual mechanism approach but we are up against in treating all these diseases as we reach the ceiling effect with what we have. We can try for higher efficacy but that is also limited by the pathology of the disease and the damage and the chronicity caused by the disease — or we can go for durability and very simply.
For example, in my patient population, my diabetic macular edema patients, over 60% of them are still working. The ability to come every month, or even every 6 weeks, every 8 weeks for injections is very limited and over what period of time. So, if you can come up with a molecule that reduces patient treatment burden, such as faricimab, I think that is one of the many, many approaches that we are all going to see in the future trying to target this disease by more than just the antibody approach.