As more countries receive approval for the use of faricimab, patients are going to continue to have good visual outcomes
The TRUCKEE study evaluated the safety and efficacy of faricimab (Vabysmo; Genentech) in a real-world setting in patients with neovascular age-related macular degeneration (nAMD).
Dr David Almeida, director of clinical research at Erie Retinal Surgery in Erie, Pennsylvania, US, reported on the drug’s performance in real-world clinical settings at the 14th Annual Congress on Controversies in Ophthalmology (COPHy), held in March in Lisbon, Portugal.
“Age-related macular degeneration is the number 1 cause of blindness in patients over 65 years of age, so it was a logical starting point. The drive and impetus for the prospective TRUCKEE study was the idea that a medication like faricimab, a biphasic compound, addresses 2 targets, vascular endothelial growth factor A (VEGF-A) and angiotensin-2,” he said.
The importance of the study is that this biphasic compound reflects how the drug might be used in clinical settings in treatment-naïve patients, those switched from faricimab to another medication and those refractory to previous treatments.
The TRUCKEE study included over 500 patients. The investigators evaluated the best-corrected visual acuity (BCVA), the central subfield thickness (CST), the degree of pigment epithelial detachment and the presence of choroidal neovascular membrane. They also evaluated the drug’s durability; that is, the length of the intervals between injections and the safety profile.
The study comprised patients who had been treated previously (90%). These included over 50% with aflibercept (Eylea; Regeneron), about 10% with ranibizumab (Lucentis; Genentech), and less than 10% with brolucizumab (Beovu; Novartis) and bevacizumab (Avastin; Genentech); about 10% of patients were treatment naïve.
The investigators evaluated the results in patients who received one and three faricimab injections. Dr Almeida explained that retina specialists may administer one injection to assess the response and then multiple injections, namely, three in the TRUCKEE study.
He reported that one injection of faricimab resulted in about a 1.1-letter improvement and a decrease of over 30 μm in the CST seen on optical coherence tomography (OCT) images. After three injections, the therapeutic effect was augmented; the investigators found additional improvements of up to 3.2 letters in BCVA and an additional CST decrease of almost 50 μm on OCT. All patients, regardless of the previous treatment or if they were treatment naïve, had anatomic improvement.
Dr Almeida commented, “The patients are going to have better anatomy in their outer and inner retina, and their vision is going to improve. When we’re trying to model a real-world study, those are the factors that come up over and over.”
He reported a patient in whom the subretinal fluid improved after switching to faricimab, and the vision improved from 20/40 to 20/30. One patient with previous recalcitrant subretinal fluid also had a nice improvement.
Intraretinal fluid is considered more dangerous in nAMD and associated with more negative prognostic outcomes in the patients with neovascular disease; the BCVA improved from 20/50 to 20/40 with the improvement in the intraretinal fluid, which had been extensive with the previous treatment.
Safety is important in any real-world study. The TRUCKEE investigators looked for new or severe safety signals to be considered.
Dr Almeida reported that after 1231 injections in 550 eyes, one patient had infectious endophthalmitis, and the vision returned to baseline after
3 weeks. A second patient had mild intraocular inflammation after the fourth faricimab injection and returned to normal with administration of topical corticosteroids.
No cases of occlusive vasculitis, retinal vasculitis, or retinal artery occlusion occurred. “This is important because that was a new signal that occurred with brolucizumab use in the real world. This was not seen with faricimab, which was very reassuring,” Dr. Almeida reported.
The study concluded with the following takeaways:
Dr Almeida concluded that as more countries receive approval for the use of faricimab, patients are going to continue to have good visual outcomes. “Regardless of whether the patient is treatment naïve or a person who has been previously stuck on or unable to extend on a previous agent, we see good tolerability in these patients,” he said.
Second, no new worrisome safety signals became apparent in the TRUCKEE
population. The investigators will continue to assess the results and compare the clinical trial registry results.
David Almeida, MD, PhD, MBA, is director of clinical research at Erie Retinal Surgery in Erie, Pennsylvania, US.