MONTREAL — Diabetic retinopathy severity and the risk of vision-threatening complications decreased significantly in patients treated with the investigational VEGF inhibitor tarcocimab, a randomized, sham-controlled study showed.
More than 60% of patients had at least a two-step improvement in the Diabetic Retinopathy Severity Scale (DRSS) at 48 weeks after five intravitreal injections of tarcocimab (two from weeks 24-48) as compared with 3.3% of patients randomized to sham injections. Sight-threatening complications — diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), and anterior segment neovascularization — occurred in 2.4% of the tarcocimab group versus 15.8% of the control group.
Central subfield thickness (CST) decreased in the tarcocimab arm but remained largely unchanged in the control arm, and visual acuity was preserved in both groups. No patients in the tarcocimab group developed endophthalmitis or intraocular inflammation, and more diabetic retinopathy-related adverse events occurred in the control group, reported Charles Wykoff, MD, PhD, of Retina Consultants of Texas in Houston, at the American Society of Retina Specialists meeting.
Results from the GLOW2 trial are consistent with those of the GLOW trial, which showed a two-step DRSS improvement in 41% of patients treated with tarcocimab and a 90% reduction in sight-threatening complications.
“We’ve seen robust efficacy and good safety with tarcocimab among patients with a broad spectrum of diabetic retinopathy, with four to five injections through 1 year, including a 6-month interval,” said Wykoff. “A multi-retina indication [biologic license application] for tarcocimab in the FDA is in preparation.”
During a discussion that followed, Wykoff acknowledged that many patients with diabetic retinal disease currently are not treated.
“I think there’s a huge population of patients that we overall are not currently treating that have slowly progressive disease, and I don’t like watching that,” he said. “But it’s a big trigger to start giving people injections in their eye, so I get the desire to wait until there’s DME or PDR to treat, and that’s what most of us do for most patients in most situations. I do think our field needs, and our patients deserve, a better way to treat and prevent.”
Moderator Jaclyn Kovach, MD, of the Bascom Palmer Eye Institute in Miami, asked Wykoff if he thought the “drug is going to be something that increases retina specialists’ interest in treating patients more prophylactically, even though vision is unchanged.”
“I don’t think any single drug is going to be a silver bullet, but I do think the field needs to move in that direction,” said Wykoff.
Kovach also noted that the GLOW2 investigators examined effects of tarcocimab in patients with and without GLP-1 agonist treatment and found no difference in outcomes. “Do you think that is a subset of patients that we need to more carefully analyze in trials, going forward?” she asked.
Historically, clinical trials have excluded patients on GLP-1 agonists or required patients to have several months of stable dosing, said Wykoff. GLOW2 is the first trial in retinal disease that had “no gating related to GLP-1 agonist use.”
“That much more reflects what’s happening in our clinics,” he continued. “If my diabetics are not on GLP-1 agonists, I’m often talking about it with them because I think there is data to support that use. It’s amazing how our patients are scared of GLP-1 agonists, and there are certainly adverse events. But they’re particularly scared of the DR [diabetic retinopathy] worsening. I think that’s exceedingly rare. In my cases, I’ve just seen people get better.”
Developed from a proprietary biopolymer conjugate platform, tarcocimab consists of 20% free antibody and 80% biopolymer, designed to achieve durable effects with extended dosing intervals.
GLOW2 included 255 patients with moderate/severe non-proliferative diabetic retinopathy or mild PDR. They were randomized to five intravitreal injections of tarcocimab — three over a 4-week interval, the fourth after a 12-week interval, and the fifth after a 24-week interval — or matching sham injections. The primary endpoint was the proportion of patients with at least a two-step improvement in DRSS at 48 weeks.
The study population had a mean age of 56, a mean hemoglobin A1c level of 8.1-8.2%, a best corrected visual acuity (BCVA) of 81-82 letters, and a mean CST of 280-286 µm. About three-fourths of the patients had moderately severe NPDR (DRSS ≤47) and 16-17% had mild PDR (DRSS 61).
The 48-week results showed almost a 20-fold difference in the number of patients who achieved a two-step improvement in DRSS (62.5% vs 3.3%, P<0.0001) and an 85% reduction in the risk of sight-threatening complications (P=0.0001). The proportion of patients achieving the primary endpoint continued to increase to the end of the study (59% prior to the week-44 dose and 62.5% at 48 weeks).
Analysis of the primary endpoint by GLP-1 agonist use showed 60% of users met the two-step improvement in DRSS, as did 64.3% of non-users. No patients in the tarcocimab arm had a two- or three-step worsening of DRSS as compared with 13.1% and 4.6% of the control group, respectively.
Mean BCVA at week 48 was 82.5 letters with tarcocimab and 82.0 letters in the control group. Mean CST at week 48 was 263.8 µm in the tarcocimab group and 288.3 µm in the control group.
Ocular adverse events up to week 48 occurred in 22.3% of the tarcocimab group versus 27.2% of the sham group, and included dry eye, vitreous floaters, diabetic retinal edema, and conjunctival hemorrhage.
