While currently there isn’t a cure for diabetic retinopathy (DR), researchers have been moving full steam ahead in developing new therapies to halt the progression and help manage this sight-threatening condition. Therefore, there were not one — but two — very informative sessions on the disease on Day 1 of the American Society of Retina Specialists (ASRS 2021) Scientific Meeting. Here, we’ll take a look at what was covered during the aptly named Diabetic Retinopathy Symposium 2, which focused on some emerging treatments, like gene therapy. This session ran the better part of two hours, so unfortunately, this article serves as a “Cliffs Notes” version — so make sure to watch the full symposium on demand at your leisure. That said, let’s dive in!
Say hello to new(er) molecules
Anti–vascular endothelial growth factor therapy (anti-VEGF) has been the first-line treatment for a variety of retinal conditions — and for good reason: It gets the job done. However, the treatment regimen can be burdensome, and some patients just don’t respond to the drug. So, in the quest to save sight, newer molecules, like faricimab and brolucizumab have been introduced into the potential paradigm — and we say, the more options, the better.
On faricimab was Dr. Caroline Baumal, who shared results from the YOSEMITE and RHINE trials which evaluated the efficacy, safety and durability in 1,891 diabetic macular edema patients (DME). We’ll begin with a short description of the drug, as shared by Dr. Baumal: “Faricimab is the first bispecific antibody designed specifically for intraocular use. It’s one molecule with two targets: It binds and neutralizes Ang-2 and VEGF-A, which are key drivers of vascular leakage, neovascularization and inflammation — and it’s this dual effect that may give rise to the potential for greater effect of vascular stability than anti-VEGF treatment alone.”
So, what did they find? According to Dr. Baumal, there were greater reductions in central subfield thickness and in faricimab-treated eyes — and more of the faricimab-treated eyes achieved absence of DME. Further — and importantly — “more faricimab patients achieved more absence of intraretinal fluid compared to aflibercept eyes at week 56, showing that there may be an additional edge of effectiveness from this bispecific unique molecule,” she added.
Indeed, the investigators found that “Faricimab was well-tolerated; intraocular inflammation event rates for faricimab were low (1.3% on average) and no cases of vasculitis or occlusive retinitis were reported.”
Next up, Dr. David Brown shared results from the KESTREL and KITE studies, which evaluated the efficacy and safety of brolucizumab in DME. To summarize: In both studies, “brolucizumab offered robust vision gains and improved anatomical outcomes with more than 50% of DME patients maintained on a q12w treatment interval after loading through Week 52, and demonstrated an overall well-tolerated safety profile.”
Getting “gene-y” with it
Gene therapy continues to create a big buzz for its potential to prolong treatment intervals and improve outcomes in certain conditions. As such, we were excited to hear about the first-time 24-week interim data from the INFINITY trial presented by Dr. Charles Wykoff. This phase 2 study was designed to assess the durability, safety, tolerability and efficacy of a single IVT injection of ADVM-022 in patients with DME.
According to Dr. Wykoff, ADVM-022 is a novel biofactory approach to gene therapy designed for continuous delivery of aflibercept following intravitreal injection. Unfortunately, not all went as planned. “INFINITY, importantly, was unmasked on May 4 due the development of a dose-limiting toxicity of hypotony necessitating surgery,” shared Dr. Wykoff, adding that this was the most unexpected, significant adverse effect.
In terms of visual acuity, he shared that improvements were observed until after week 24 — at that point, there was a downward trajectory in the high-dose population related to adverse events.
“When considering ocular adverse events, nearly all of the ADVM-022 treatment patients developed anterior IOI (intraocular inflammation), a majority developed an iris-related events, and a few had posterior IOI.
“While these events were consistent with what has been reported in OPTIC, overall, the proportion of patients — and the intensity of these events — both appear to be meaningfully increased in this INFINITY dataset compared to OPTIC,” he continued, adding that there were three cases of hypotony, all in the high-dose population, that required surgery.
He said that a comprehensive approach is underway to better understand these adverse events and this dose-loading toxicity. “From this interim analysis of the INFINITY study we have learned that ADVM-022 dose and disease state appear to play a very meaningful role in determining the therapeutic window to balance safety and efficacy,” said Dr. Wykoff. And due to these events, he concluded that moving forward, ADVM-022 development will focus on neovascular AMD and not DME, as well as lower doses of ADVM-022.
Short and sweet
We’re low on space, but high on content — so bear with us while we summarize a few more key points.
Dr. Sophie Bakri presented data from a meta-analysis of five ranibizumab trials and asked: What is the clinical significance of improving diabetic retinopathy for vision outcomes? She reported that in “patients receiving monthly ranibizumab for DR, greater DR severity improvements were associated with better vision outcomes and reduction in CST.” Further, in these patients, greater DRSS (diabetic retinopathy severity scale) improvement was significantly associated with trends for better vision and anatomic outcomes.
Telemedicine has been increasing in use, and now, along with the development of artificial intelligence (AI), this combination could result in improved outcomes. On this topic, Dr. Andrew Barkmeier shared real world telemedicine outcomes for DR screening with AI-based image analysis, reflex dilation and image overread protocol in a primary care setting. While they found that most patients over 60-years-old require dilation for successful image interpretation, the main conclusion was this: “Combining AI-based image analysis with a formal reflex dilation protocol and manual overread of positive results may allow for safe and efficient DR screening — while minimizing follow-up clinic visits.”
For more on these topics — as well as the ones we just couldn’t fit in this space — make sure to check out the symposium on-demand.
Editor’s Note: A version of this article was first published in CAKE & POST (ESCRS and ASRS 2021 Edition), Issue 2.