Faricimab for nAMD and DME: Welcome to the real world

Arshad M. Khanani, MD, MA, FASRS, discusses rapid improvement with faricimab in treatment-naïve and previously treated patients with nAMD and DME.

Faricimab-svoa (Vabysmo, Genentech) received FDA approval to treat neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DME) based on the results of large randomised clinical trials with largely homogeneous patient populations. But questions remain about how the drug performs in the real world when patients in clinical settings vary markedly from those in the clinical trials.

Arshad M. Khanani, MD, MA, FASRS, director of clinical research at Sierra Eye Associates and clinical associate professor at the University of Nevada, Reno School of Medicine, discussed his observations in the Ophthalmology Times Europe Rapid Readout series.

“Why do we need real-world data? It’s an important point because clinical trials have strict inclusion and exclusion criteria,” he emphasised. “We don’t know both how efficacious the drug will be and the safety when numerous patients, who differ from those in the clinical trials, receive the drug.” The major findings involving real-world data amassed thus far are enumerated here:

One faricimab injection causes rapid improvement in all anatomic parameters, ie, intraretinal fluid, subretinal fluid and pigment epithelial detachment (PED) in treatment-naïve and previously treated patients with neovascular AMD and DME. The TRUCKEE study, a collaborative, non–pharmaceutical company supportive, physician-driven study showed that after one injection in treatment-naïve patients, rapid improvement in central subfield thickness (CST) and PED reductions were seen along with a trend toward increased vision in treatment-naïve patients, according to Dr Khanani.

Most patients switching from aflibercept 2 mg (Eylea, Regeneron Pharmaceuticals) to faricimab experience reduced anatomic parameters and stable/improved vision with potential for extended treatment intervals. In the TRUCKEE study, 1,007 eyes switched from aflibercept to faricimab had improved anatomic parameters and stable vision against similar intervals before and after faricimab. In naïve patients and those switched to faricimab, 25% to 30% of patients had resolution of intraretinal and subretinal fluid.

In the TRUCKEE real-world study, patients received 6 faricimab injections. The results showed almost a 50-µm improvement in CST, which is very clinically significant in these patients who are receiving frequent treatments of aflibercept before switching to faricimab, according to Dr Khanani.

The TRUCKEE substudy data showed that 262 eyes had an improvement of almost 120 nL of fluid after one injection; fluid improved in 72% of eyes after one injection. Evaluation of naïve and aflibercept-treated patients showed that from 60% to 70% of patients had improvement after one injection. Fluid status continued to improve with continued treatment. He also said that after 3 loading doses, treatment interval increases and fluid continues to decrease.

It is crucial to ensure that faricimab is drawn accurately and administered without any air bubbles. The presence of air bubbles may result in overdosing of the patients and lower efficacy than that seen in clinical trials.

Faricimab had a favorable safety profile with rates of inflammation and endophthalmitis comparable to other commonly used approved treatments. The TRUCKEE study with 2,622 eyes (2,212 patients treated with faricimab) showed a low rate of intraocular inflammation and endophthalmitis, most of which were mild and resolved with topical +/– oral steroids. In most cases, these patients were rechallenged with faricimab because the disease was not controlled with other anti-VEGF drugs, with no recurrent intraocular inflammation. No cases of retinal vasculitis or retinal artery occlusion developed.

Finally, ophthalmologists should generate real-world data on efficacy and safety for any new drug approved to treat retinal diseases to determine how these agents fit into clinical practice.