BREAKING NEWS: Faricimab approved by U.S. FDA for treatment of wet AMD, DMO

Genentech’s treatment of faricimab is the first and only FDA-approved medicine targeting two distinct pathways, angiopoietin (Ang)-2 and vascular endothelial growth factor (VEGF)-A, that often cause retinal diseases that may cause visual loss.

On Friday, January 28, the U.S. Food and Drug Administration (FDA) approved Vabysmo™ (faricimab-svoa, Genentech), a bispecific antibody for the treatment of wet age-related macular degeneration (AMD) and diabetic macular oedema (DMO). Faricimab is the first and only FDA-approved drug to target two distinct pathways, Ang-2 and VEGF-A, that often cause retinal disease that may lead to visual loss.

“Vabysmo represents an important step forward for ophthalmology. It is the first bispecific antibody approved for the eye and a major advance in treating retinal conditions such as wet AMD and diabetic macular oedema,” Charles Wykoff, MD, PhD, director of research at Retina Consultants of Texas in Houston and a faricimab Phase III investigator, said in a statement. “With Vabysmo, we now have the opportunity to offer patients a medicine that could improve their vision, potentially lowering treatment burden with fewer injections over time.”

Genentech also submitted a Marketing Authorization Application for faricimab for the treatment of nAMD and DMO, which the European Medicines Agency has accepted.1 Additionally, the FDA is reviewing Genentech’s application fordiabetic retinopathy.

In the release, Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, faricimab “provides a new approach to treating vision-threatening retinal conditions through a mechanism of action that targets two pathways simultaneously.”

“This is our second FDA approval in ophthalmology in recent months, underscoring our commitment to people living with retinal conditions,” he added in the statement.

For retina specialists, the approval is welcome news and offers a new treatment option for patients.

Lawrence Singerman, MD, FACS, of Retina Associates of Cleveland and a clinical professor of ophthalmology at Case Western Reserve University and Bascom Palmer Eye Institute, said he has been anticipating the announcement of FDA approval for faricimab.

“After giving presentations of data from the studies, and witnessing those presented by other investigators It is clear to me that this drug offers impressive efficacy and extended duration of action combined with an excellent safety profile,” he said. “This drug should ease the treatment burden on our patients with Wet AMD and DME.”

“The forthcoming availability of faricimab is a refreshing way to kick off 2022 for retina specialists and patients with macular disease alike,” said Andrew A. Moshfeghi, MD, MBA, associate professor of ophthalmology, University of Southern California.

Moshfeghi noted that faricimab appears to offer patients the chance to have more robust control of their macular disease and the potential for a longer treatment benefit.

“Having a new therapy for which approximately half of patients were able to be safely treated as infrequently as every 4 months is a big step forward for patients with chronic macular diseases like nAMD and DME—common conditions that traditionally require very frequent injections (every 1 to 2 months) with standard anti-VEGF monotherapy alone,” he said.

“I think the landscape for faricimab could be an exciting one for both exudative neovascular age-related macular degeneration and diabetic macular edema, particularly with sustaining and extending therapy for patients currently requiring high injection frequency,” said Mark P. Breazzano, MD, an assistant professor of ophthalmology at Wilmer Eye Institute, Retina Division, Johns Hopkins School of Medicine. “The data appear to show efficacy and durability with four-month treatment intervals for many of these patients. However, like any new treatment, it remains important to be cautious and continue monitoring for any safety signals that may follow FDA approval.”

According to Ian C. Han, MD, an associate professor, Institute for Vision Research, Ophthalmology and Visual Sciences, University of Iowa Hospital and Clinics, even with available treatment options, some patients reach a plateau of response to treatment with currently available agents, and the need for frequent office visits for injections continues to be a substantial burden, one that has only been exacerbated with the challenges of the pandemic.

“The current injectable medications on the market target vascular endothelial growth factor (VEGF), which plays a primary role in new blood vessel growth,” he said. “However, we have known for a while now that VEGF levels can modulate over time, and plenty of other factors beyond VEGF play a role in blood vessel formation and stabilization.”

Han noted that faricimab is the first FDA-approved agent to target not only VEGF but the angiopoietin (Ang) and Tie receptor pathway, which plays an important role in vascular stability and permeability.

“Faricimab has the potential to decrease the treatment burden for patients with two conditions that we see the most (wet AMD and DME). It also represents an important step in moving beyond "just anti-VEGF" for treatment of these conditions, potentially paving the way for other drugs in the pipeline,” Han said. “As always with a new drug, ophthalmologists will need to translate the protocols from clinical trials to their everyday practice, including the varying treatment schedules (between one to four months in the phase 3 studies).”

Han added FDA-approval is a necessary and important step to bringing a new treatment to clinic.

“As we have recently been reminded, clinicians will need to evaluate the efficacy (and safety) of faricimab in their own patients to decide on the best treatment among the several now available for wet AMD and DME,” he said.

Faricimab met its primary endpoints for a variety of studies: TENAYA and LUCERNE and its extension study AVONELLE X, which assessed the long-term safety and efficacy of faricimab for the treatment of wet AMD. YOSEMITE and RHINE and the extension study RHONE X measured the safety and efficacy of faricimab for the treatment of DMO.

Extension studies AVONELLE X and RHONE X are still underway to determine the long-term safety and efficacy of wet AMD and DM), respectively. RHONE X is expected to conclude in August 2023, and AVONELLE X is expected to conclude in August 2024.2,3

The COMINO and BALATON trials are currently evaluating the safety and efficacy of faricimab in patients with macular oedema secondary to central retinal vein occlusion (RVO) and branch RVO. The study is expected to conclude in fall 2023.4

TENAYA and LUCERNE trials

The results of the phase III TENAYA and LUCERNE trials showed that faricimab (Hoffman-La Roche) INTERESTING-2 DIFFERENT MANUFACTURERS? met the primary efficacy endpoints of noninferiority to aflibercept (Eylea, Regeneron Pharmaceuticals) in the change in the best-corrected visual acuity (BCVA), durability, and safety for treating patients with neovascular AMD, according to Robyn Guymer, ADD DEGREE? a professor of ophthalmology at Melbourne University and deputy director of the Centre for Eye Research Australia in Melbourne.

These 2 clinical trials are large identical randomized, double-masked, investigations that are evaluating the dual inhibition of angiopoietin-2 and VEGF-A by faricimab.

Patients in these 112-week studies were treatment-naïve and randomized 1:1 to faricimab 6.0 mg up to every 16 weeks after 4 initial every-4-week doses or aflibercept 2.0 mg every 8 weeks after 3 initial every-4-week doses.

After the initial dosing and assessments of the disease activity, the patients receiving faricimab were treated at fixed intervals, i.e., every 16 weeks, every 12 weeks, or every 8 weeks.

The patients treated with faricimab then followed a personalized treatment interval, that is, a protocol-driven treat-and-extend regimen with interval adjustment that was based on individualized treatment responses as assessed by the prespecified anatomic and functional criteria at study drug dosing visits up to week 108.

The primary efficacy endpoint was the change in the BCVA compared with baseline averaged over weeks 40, 44, and 48 and compared with aflibercept.

The secondary safety endpoints were the proportions of patients treated every 8, every 12, and every 16 weeks; the proportion of patients who had increases of 15 letters or more or who did not have losses of 15 letters or more; and the changes in the BCVA and central subfield thickness (CST) over time.

The safety endpoints were the incidence and severity and non-ocular adverse events.

YOSEMITE and RHINE trials

The 1-year results of the ongoing 2-year YOSEMITE and RHINE trials showed favorable results for faricimab for treating DMO. The visual gains achieved with every-16-week dosing were non-inferior to those of aflibercept (Eylea) dosed every 8 weeks.

The anatomic gains also favored faricimab compared with aflibercept. Faricimab also demonstrated a good safety profile with very low rates of inflammation. John Wells, MD, from the Palmetto Retina Center, West Columbia, SC, presented the results at the Association for Research in Vision and Ophthalmology’s virtual 2021 annual meeting on behalf of the YOSEMITE and RHINE investigators.

The YOSEMITE and RHINE trials, which are identical, randomized, double-masked studies compared the efficacy, durability, and safety of faricimab with aflibercept in patients with center-involving DMO who were either treatment-naïve or received previous treatment with anti-VEGF therapy.

Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks after 6 initial every-4-week doses; faricimab 6.0 mg treated according to a personalized treatment interval (PTI) based on the treat-and-extend concept after 4 initial every-4-week doses; or aflibercept 2.0 mg every 8 weeks after 5 initial every-4-week doses.

The primary efficacy endpoint was the mean change in the BCVA from baseline averaged over study weeks 48, 52, and 56. The secondary endpoints were the proportion of patients with a 2-step or more improvement in the Early Treatment Diabetic Retinopathy Diabetic Retinopathy (ETDRS) Severity Scale ) from baseline, the proportion of patients with a 15 or greater gain in ETDRS letters from baseline, the change in CST from baseline, and the proportion of patients in the PTI arm receiving doses every 4, every 8, every 12, or every 16 weeks at 1 year.

References
1. FDA accepts application for Roche's faricimab for the treatment of neovascular age-related macular degeneration (NAMD) and diabetic macular edema (DME). Roche. https://www.roche.com/investors/updates/inv-update-2021-07-29b.htm
2. A study to evaluate the long-term safety and tolerability of Faricimab in participants with neovascular age-related macular degeneration. https://clinicaltrials.gov/ct2/show/NCT04777201
3. A study to evaluate the long-term safety and tolerability of Faricimab in participants with diabetic macular edema. https://clinicaltrials.gov/ct2/show/NCT04432831
4. A study to evaluate the efficacy and safety of Faricimab in participants with macular edema secondary to branch retinal vein occlusion. https://clinicaltrials.gov/ct2/show/study/NCT04740905