European Commission approves faricimab for nAMD, DME

Roche today announced the European Commission (EC) has approved faricimab (Vabysmo) for the treatment of neovascular or ‘wet’ age-related macular degeneration (nAMD) and visual impairment due to diabetic macular edema (DME).

According to teh company's news release, these retinal conditions are two of the leading causes of vision loss worldwide, affecting more than 40 million people ^1,2,3,4

Ramin Tadayoni, MD, PhD, head of the ophthalmology department, Lariboisière, Saint-Louis and Rothschild Hospitals, Paris, France, and European Society of Retina Specialists (EURETINA) president elect, noted in a news release that a number of people with nAMD and DME struggle to keep up with the monthly eye injections and physician visits, often associated with current standards of care, and unfortunately their vision may suffer as a result of undertreatment.

“For people in Europe living with these conditions, today’s approval offers the first new mechanism of action in over a decade; one which could improve and protect their vision with fewer injections over time,” he said in the release.

According to the news release, faricimab is the only injectable eye medicine approved in Europe with phase III studies supporting treatment at intervals of up to four months for people living with nAMD and DME.^5,6,7

Today’s approval is based on results across four phase III studies in two indications, involving 3,220 patients: TENAYA and LUCERNE in nAMD at year one, and YOSEMITE and RHINE in DME up to two years. The studies showed that people treated with faricimab, given at intervals of up to four months, achieved similar vision gains and anatomical improvements compared to aflibercept given every two months.^6,7,8 The totality of data across all four studies at two years showed that more than 60% of people treated with faricimab were able to extend treatment to every four months, while improving and maintaining vision. Additionally, up to two years, people with nAMD and DME treated with faricimab received 33% (10 vs. 15) and 21% (11 vs. 14) fewer median number of injections compared to aflibercept, respectively.^6,9

Faricimab, a bispecific antibody, is uniquely engineered to target and inhibit two disease pathways, linked to a number of vision-threatening retinal conditions, by neutralizing angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), to restore vascular stability. By independently blocking both pathways involving Ang-2 and VEGF-A, faricimab is designed to stabilize blood vessels and thereby reduce inflammation, leakage and abnormal vessel growth (neovascularization) more than inhibition of VEGF-A alone.7 This sustained blood vessel stabilization may improve disease control, vision and anatomical outcomes for longer.^7,8

Faricimab is now approved in the European Union and nine other countries around the world, including the US, Japan, and the UK, for people living with nAMD and DME, and submissions to other regulatory authorities are ongoing.^5,10,11,12 Globally, more than 100,000 faricimab doses have been distributed for treatment of these conditions to date.¹³ Roche also continues to explore areas where faricimab has the potential to deliver additional benefits to patients, including retinal vein occlusion.

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. Bright Focus Foundation. Age-Related Macular Degeneration: Facts & Figures. [Internet; cited September 2022]. Available from: https://www.brightfocus.org/macular/article/age-related-macular-facts-figures.
2. Connolly E, et al. Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population. Br J Ophthalmol. 2018;102:1691–5.
3. Yau JWY, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556-64.
4. Heier JS, et al. The Angiopoietin/Tie pathway in retinal vascular diseases: a review. Retina-J Ret Vit Dis. 2021;41:1-19.
5. European Medicines Agency. Summary of Product Characteristics, Vabysmo, 2022.
6. Wells JA, et al. Faricimab in Diabetic Macular Edema: Two-Year Results From the Phase III YOSEMITE and RHINE Trials. Presented at: Angiogenesis, Exudation and Degeneration 2022.
7. Heier JS, et al. Efficacy, durability and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): Two randomised, double-masked, phase III, non-inferiority trials. The Lancet. 2022;399(10326):741-755, https://doi.org/10.1016/S0140-6736(22)00010-1.
8. Wykoff C, et al. Efficacy, durability and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with DME (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. The Lancet. 2022;399(10326):729-740, https://doi.org/10.1016/S0140-6736(22)00018-6.
9. Khanani A, et al. Faricimab in Neovascular Age-Related Macular Degeneration: Year 2 Efficacy, Safety and Durability Results From the Phase III TENAYA and LUCERNE Trials. Presented at: 2022 American Society of Retina Specialists Annual Scientific Meeting; 2022.
10. U.S. Food and Drug Administration (FDA). Highlights of prescribing information, Vabysmo. 2022. [Internet; cited September 2022]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761235s000lbl.pdf
11. UK Medicines and Healthcare products Regulatory Agency approves faricimab through international work-sharing initiative. [Internet; cited September 2022]. Available from: https://www.gov.uk/government/news/mhra-approves-faricimab-through-international-work-sharing-initiative.
12. Chugai Obtains Regulatory Approval for Vabysmo, the First Bispecific Antibody in Ophthalmology, for Neovascular Age-related Macular Degeneration and Diabetic Macular Edema. [Internet; cited September 2022]. Available from: https://www.chugai-pharm.co.jp/news/cont_file_dl.php?f=220328eVabysmo_DME_nAMD_approval.pdf&src=[%0],[%1]&rep=130,909

13. Roche data on file