Bispecific Antibody Compares Favorably With Anti-VEGF for Retinal Disease

SAN ANTONIO — The bispecific antibody faricimab performed at least as well as standard anti-VEGF therapy for age-related macular degeneration (AMD) and diabetic macular edema (DME) with increased durability, data from four randomized trials showed.

The dual-targeted agent achieved noninferiority to aflibercept (Eylea) for best-corrected visual acuity (BCVA) and reduction in central subfield thickness (CST) in AMD with durability up to 16 weeks versus 8-week dosing with aflibercept. Patients with DME had similar BCVA with the two therapies but greater reductions in CST with faricimab, also with durability for as long as 16 weeks, the data showed.

Faricimab was well tolerated in all four trials, including no cases of vasculitis or occlusive retinitis, as reported here at the American Society of Retina Specialists meeting.

AMD Results

“Visual acuity was noninferior despite the fact that many patients in the faricimab arm were receiving dosing at 12 and 16 weeks,” said Karl Csaky, MD, PhD, of the Retina Foundation of the Southwest in Dallas, who reported the AMD data. “Over three quarters of the patients could maintain improvement over 12- or 16-week intervals. Visual gains were immediate and maintained over the course of 48 weeks of follow-up. The [CST] results were similar to aflibercept, a dramatic reduction and maintenance over the course of 48 weeks, even though patients were receiving less faricimab.”

Faricimab simultaneously inhibits Ang-2 and VEGF-A. Collectively, the dual inhibitory activity stabilizes vessels, reduces leakage and inflammation, and inhibits neovascularization. Csaky reported the 48-week outcomes from the phase III TENAYA and LUCERNE trials comparing faricimab and aflibercept in patients with neovascular AMD.

Eligible patients had BCVA of 20/32 to 20/320 and choroidal neovascularization. They were randomized to aflibercept every 8 weeks or to faricimab at dosing intervals up to every 16 weeks. The primary endpoint was BCVA averaged from the week 40, 44, and 48 visits. A key secondary endpoint was the proportion of patients who received faricimab every 12 or 16 weeks.

The two trials included a total of 1,329 patients. In TENAYA 34.0% of patients received faricimab at 12-week intervals and 45.7% received the antibody every 16 weeks. The numbers in the LUCERNE trial were 32.9% and 44.9%, respectively.

BCVA improvement from baseline with faricimab averaged 5.8 letters in TENAYA and 6.6 letters in LUCERNE. BCVA improvement in aflibercept-treated patients averaged 5.1 letters in TENAYA and 6.6 in LUCERNE. Similar proportions of patients gained ≥15 letters and avoided BCVA declines ≥15 letters. More than 90% of patients in both treatment arms had vision stabilization throughout follow-up in both trials.

Reduction in CST from baseline (a secondary endpoint) averaged 128 to 130 μm with faricimab and 136 to 137 μm with aflibercept.

Adverse events (AEs), serious AEs, and ocular and non-ocular AEs occurred in similarly low proportions of patients in both treatment arms, said Csaky. Intraocular inflammation occurred in 2% of faricimab-treated patients and 1.2% of the aflibercept population.

DME Results

Similar patterns of safety and efficacy played out in the phase III YOSEMITE and RHINE trials comparing faricimab and aflibercept in patients with DME. The two trials involved a combined total of 1,891 patients, who were randomized to aflibercept every 8 weeks, faricimab every 8 weeks, or faricimab personalized treatment interval (PTI).

Patients assigned to faricimab PTI began treatment at 4-week intervals, which was maintained until the first reduction in CST to <325 μm (after at least four doses). At that point, an automated standardized algorithm was used to adjust dosing intervals as needed to maintain the improvement, ranging from 4 to 16 weeks, said Caroline Baumal, MD, of Tufts Medical Center in Boston.

The primary endpoint was BCVA from baseline, averaged over visits at weeks 48, 52, and 56, and the trials were statistically powered for noninferiority. Both trials met the primary endpoint, as BCVA improved by 11.6 and 10.8 letters with PTI dosing in YOSEMITE and RHINE. That compared with 10.7 and 11.8 letters with faricimab q8w, and 10.9 and 10.3 letters with aflibercept.

Among patients assigned to faricimab PTI in both trials, more than 50% maintained BCVA with 16-week dosing intervals, and more than 20% did so with 12-week dosing intervals, said Baumal.

Faricimab led to greater reductions in CST in both trials. Baseline CST ranged from 471 to 492 across treatment groups in the two trials. Faricimab PTI was associated with mean reductions of 206.6 and 195.8 μm in YOSEMITE and RHINE, respectively, as compared with 196.5 and 187.6 μm with faricimab q8w, and 170.3 and 170.1 μm with aflibercept (P<0.05 aflibercept versus each of the faricimab dosing intervals).

Additionally, significantly more patients treated with faricimab achieved absence of DME at week 56 as compared with aflibercept (P<0.05 for all comparisons). Baumal reported that 87% and 90% of faricimab PTI patients were DME free at 56 weeks in YOSEMITE and RHINE, respectively, as were 82% and 87% of patients treated with faricimab q8w and 65% and 73% of aflibercept-treated patients.

The safety profile of the three treatment arms was similar to that seen in the AMD trials, she said.