Faricimab, an experimental drug, could reduce the number of injections needed to treat both age-related macular degeneration (AMD) and diabetic macular edema (DME), phase 3 trials suggest.
Faricimab’s mechanism of action appears to make it longer-lasting than drugs most often currently used to treat AMD and DME, said Jayanth Sridhar, MD, associate professor of clinical ophthalmology at the Bascom Palmer Eye Institute in Miami, Florida, who was not involved in the trials.
“I think it’s very exciting because of the durability component,” he told Medscape Medical News.
In addition, he said, the drug’s safety profile was comparable to aflibercept (Eylea, Regeneron). And it did not show the elevated rates of intraocular inflammation seen with brolucizumab (Beovu, Novartis), which has also been touted for its durability.
Faricimab is being developed by Genentech/Roche, and two Genentech consultants presented data on the Tenaya and Lucerne trials in AMD and the Yosemite and Rhine trials in DME at the Association for Research in Vision and Ophthalmology (ARVO) 2021 annual meeting.
The other drugs used in intravitreal injection to treat AMD and DME — aflibercept, brolucizumab, ranibizumab (Lucentis, Genentech), and bevacizumab (Avastin, Genentech) — block vascular endothelial growth factors (VEGF). Faricimab also blocks VEGF, but in addition it blocks angiopoietin-2 (Ang-2).
VEGF and Ang-2 both promote the healthy development of blood vessels, but become dysregulated in AMD and DME, leading to unhealthy proliferation and leakage of retinal blood vessels. “So, blocking Ang-2, which is elevated in those diseases, makes sense to stabilize blood vessels,” said Arshad M. Khanani, MD, MA, of Sierra Eye Associates in Reno, Nevada, and first author of the AMD studies.
In the two identical AMD trials, the researchers randomly assigned 1329 people with AMD to receive either 6.0 mg of faricimab or 2.0 mg of aflibercept through intravitreal injections administered at fixed intervals.
After administering three loading doses 4 weeks apart, the investigators injected the aflibercept patients every 8 weeks.
After administering four loading doses 4 weeks apart, the investigators evaluated the patients receiving faricimab at weeks 20 and 24. Those who had active disease at week 20 received a dose then, and every 8 weeks after that. Those with active disease that first returned at week 24 received doses that week and every 12 weeks after that. And those who had no active disease at weeks 20 or 24 received doses every 16 weeks.
Almost half of the people (45.7% in Tenaya and 44.9% in Lucerne) received their doses every 16 weeks. About a third (34.0% in Tenaya and 32.9% in Lucerne) received doses every 12 weeks.
At the end of a year, the gains in best-corrected visual acuity (BCVA) were almost the same between the faricimab and aflibercept groups. Reductions in central subfield thickness were comparable.
The percentage of patients with treatment-related ocular adverse events was about 3% and almost the same in the aflibercept and faricimab groups. The percentage of patients receiving faricimab who experienced any intraocular inflammation (excluding endophthalmitis) was 1.5 in the Tenaya study and 2.4 in the Lucerne study. The corresponding percentages for aflibercept were 0.6 and 1.8.
If patients can get the same result with fewer injections, they may be more inclined to return for all the doses they need, and may be able to maintain their visual acuity for a longer time, Khanani said. “So, that’s why it’s a big deal. It’s also valuable for physicians and offices to see these patients less often and do less injections, so they can cater to other patients.”
Results were similar in the two identical DME trials, which had a total of 1891 patients assigned to three treatment arms: aflibercept at fixed 8-week intervals, faricimab at 8-week intervals, or faricimab in a treat-and-extend regimen with dosing intervals ranging up to 16 weeks.
Intervals were extended in the treat-and-extend arms whenever patients’ central subfield thickness dropped below 325 μm. About half the patients (52.8% in Yosemite and 51.0% in Rhine) reached dosing of every 16 weeks, and one in five (21.0% in Yosemite and 20.1% in Rhine) reached dosing of every 12 weeks.
At the end of a year, as in the AMD trials, the improvements in BCVA were similar among all the groups in the two DME trials.
On the other hand, improvements in central subfield thickness were greater for faricimab than for aflibercept in the DME trials. For example, in Yosemite, the patients receiving faricimab every 8 weeks lost 206.6 μm, those receiving faricimab on the treat-and-extend regiment lost 196.5 μm, and those receiving aflibercept lost 170.3 μm. “Certainly these anatomic differences seem pretty important,” first author John A. Wells, MD, of the Palmetto Retina Center in Columbia, South Carolina, told Medscape Medical News.
Fewer than 5% of patients had any treatment-related ocular adverse event and the proportions were similar between the aflibercept and faricimab groups.
The percentages of patients with severe intraocular inflammation were 1.9 in Yosemite aflibercept group and 2.2 in the Rhine aflibercept group. It ranged from 3.4 to 4.8 in the faricimab groups.
Despite these encouraging results, Sridhar said he expects clinicians to approach faricimab carefully after the experience with brolucizumab where the risk of adverse events was not clear until after the drug came on the market.
Khanani disclosed financial relationships with Adverum, Allergan, Chengdu Kanghong, Genentech, Gyroscope, Kodiak, Novartis, Recens Medical, Regenxbio, and Roche. Wells disclosed relationships with Adverum, Genentech, Roche, Alimera, Bayer, Iveric Bio, Kodiak, Neurotech, and Regeneron. Sridhar disclosed a relationship with Regeneron.
Association for Research in Vision and Ophthalmology (ARVO) 2021: “Faricimab in neovascular age-related macular degeneration: 1-year efficacy, safety, and durability in the phase 3 TENAYA and LUCERNE trials,” presented May 6, 2021; “Efficacy, durability, and safety of faricimab in diabetic macular edema (DME): one-year results from the phase 3 YOSEMITE and RHINE trials,” presented May 1, 2021.
Laird Harrison writes about science, health, and culture. His work has appeared in national magazines, in newspapers, on public radio, and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at lairdharrison.com or follow him on Twitter: @LairdH.