Treating AMD and DME with faricimab: A therapy with lower treatment burden

Age-related macular degeneration (AMD) and diabetic macular edema (DME) affect the quality of life of patients diagnosed with the disease, despite the availability of the latest treatment technologies.

Age-related macular degeneration (AMD) and diabetic macular edema (DME) affect the quality of life of patients diagnosed with the disease, despite the availability of the latest treatment technologies.

Caroline Baumal, MD, a professor of ophthalmology and codirector of the Retina Service at the New England Eye Center) in Boston, Massachusetts, and David Eichenbaum, MD, a collaborative associate professor of ophthalmology at the University of South Florida Morsani College of Medicine in Tampa, discussed faricimab (Vabysmo; Genentech) as a treatment for these 2 markedly different diseases.

Treatment selection

Eichenbaum and Baumal emphasized the importance of shared decision-making by patients and physicians. Factors that are important to Baumal when she considers treatment options are durability, patient preferences regarding follow-up, and most importantly, safety. The AMD population tends to be older and frail, and the DME population has comorbidities; in both groups, adverse events such as inflammation and vasculitis can result in development of other issues.

Eichenbaum said the treatment decision does not always rest with the details of a medication, as patients are interested in options that affect their lifestyle, injection tolerance, adherence to the treatment plan, and the risk of adverse events.

Faricimab treat-and-extend protocol

Results in the TENAYA (NCT03823287) and LUCERNE (NCT03823300) trials, in which faricimab was evaluated for treating wet AMD in treatment-naïve patients, showed that 60% could be treated every 16 weeks and approximately 80% could be treated every 12 weeks or longer. This decreased the treatment burden to 10 injections over the 2-year treatment course compared with 15 injections in patients treated with aflibercept (Eylea; Regeneron Pharmaceuticals, Inc), Eichenbaum explained.

Baumal pointed out that the studies identified patients who need frequent treatment for the first 60 weeks, followed by a protocol-driven, treat-and-extend regimen started out to 12 weeks. Additionally, the median number of faricimab injections was lower; this predictive ability regarding the patient response may provide positive encouragement.

AMD and DME clinical trial results

The mechanism of action (MOA) of faricimab (ie, vascular stabilization resulting from inhibition of angiopoietin-2) may be responsible for the extended treatment regimens for wet AMD based on preclinical data. In patients with DME, the optical coherence tomography (OCT) results showed patients had less intraretinal fluid, possibly indicating a dual MOA of faricimab, Baumal said.

In the YOSEMITE (NCT03622580) and RHINE (NCT03622593) studies in patients with DME, the personalized treatment interval (PTI) started in year 1 and continued throughout year 2 in the PTI arm. Extended dosing went to 16 weeks in year 1 and increased in proportion through year 2 with preservation of gains in best corrected visual acuity.

Baumal believes the key finding is the reduced central retinal thickness. She also said the breakdown of the diabetic retinopathy severity scores may also show the dual MOA of faricimab.

Two 4-year extension studies, AVONELLE-X (NCT04777201), which is the long-term extension trial of TENAYA and LUCERNE; and the RHONE-X trial (NCT04432831), which is the extension study of YOSEMITE and RHINE, will determine, respectively, the extended durability and safety in AMD and help assess long-term safety, efficacy, and durability of faricimab in DME.

Faricimab in clinical practice

In commenting on the practical application of a new drug in clinical practice, Eichenbaum uses new agents on hard-to-treat patients first (ie, patients who need frequent injections with existing agents to obtain increased durability). He also used faricimab in treatment-naïve patients fairly soon after its commercialization to “test-drive” it and see whether it works as in the clinical trials.

In relatively dry wet AMD cases, Eichenbaum uses faricimab to get better extension. For treatment-naïve patients, he is testing more personalized treatments and 4-week extensions. In DME, he uses faricimab in patients who still have wet retinas, despite treatment to achieve better efficacy. He uses corticosteroids in these patients, but corticosteroids are not well suited for all.

Baumal said she uses faricimab in treated patients who want longer treatment intervals. In previously treated patients who do not respond completely, she may use faricimab to determine a possible additional effect or whether they are refractory to treatment. She also noted that in treatment-naïve patients who have received only a few injections, she is pleased with their responses thus far.

Unmet needs in DME and AMD

One unmet need is improving the representation of patients in clinical trials, Eichenbaum said. The phase 4 ELEVATUM trial (NCT05224102) is evaluating faricimab in Black and Brown patients.

Baumal would also like to lower the treatment burden for patients while maintaining safety. “An agent that lasts 3 to 4 months would be ideal,” she said.

Home OCT monitoring may fill the gaps between examinations. However, both physicians mentioned the importance of maintaining patient relationships over time.

Take-home points for treating wet AMD and DME

When considering treatments for frequently seen retinal diseases, Baumal said “efficacy, durability, and safety are the key drivers of therapeutic choices in retina. Faricimab has met the standards for efficacy and safety and has the potential for increased durability to benefit patients.”

Eichenbaum added that communication with patients is a key element. “Educating patients about their disease, spending time with them, and making a shared decision regarding their preferences will achieve their commitment and treatment adherence,” he said. “Building rapport, especially with patients with diabetes, will eliminate some problems with follow-up.”

David Eichenbaum, MD

E: deichenbaum@rvaf.com

Eichenbaum is a collaborative associate professor at the University of South Florida Morsani College of Medicine in Tampa. He is also in private practice in Tampa Bay, Florida. He is a consultant/advisor to Genentech.

Caroline Baumal, MD

E: CBaumal@tuftsmedicalcenter.org

Baumal is professor of ophthalmology and codirector of the Retina Service at the New England Eye Center in Boston, Massachusetts. She is a consultant to Genentech.