Published in Retina
Recent Advancements in the Treatment of Wet AMD
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In this article, ophthalmologists can review recent developments in the treatment of wet age-related macular degeneration (AMD).
One of the primary goals of current retina research is to develop different treatment modalities with improved durability but equal safety and efficacy.
In our previous article, we discussed anti-VEGF medications, which halt the effects of vascular endothelial growth factor (VEGF) on ocular diseases and thereby reduce neovascularization, vascular leakage, and scar formation.
However, one of the major considerations is the treatment burden for patients, as some patients need intravitreal injections up to every 4 weeks.
In this article, we discuss recent advancements in the treatment of wet (exudative) age-related macular degeneration (wet AMD) and gain insight into the promising potential of faricimab (Vabysmo), an intravitreal anti-VEGF drug approved for wet-AMD and macular edema.
We also discuss why the first portal-device system, Susvimo, was recently voluntarily recalled.
Faricimab (Vabysmo) is an intravitreal injection for patients with neovascular AMD and diabetic macular edema. This drug has a mechanism of action that has two separate targets: binding and inhibiting VEGF-A and binding and inhibiting angiopoietin-2.1 This drug was approved by the FDA for use as of January 28, 2022.
Faricimab is administered via 6mg intravitreal injections every 8 to 16 weeks and has been shown to improve the adjusted mean best-corrected visual acuity (BCVA) change to +6.2. Compared to aflibercept, this drug is administered via 2mg intravitreal injections every 8 weeks with an adjusted mean BCVA change of +5.9 letters.2 As far as efficacy goes, based on this study, faricimab is administered less frequently than aflibercept, with an increase in average mean BCVA change throughout the 48-week trial established by Genentech.
Additionally, results have been promising in the potential for the administration of faricimab every 4 months with proportionate improvements in vision compared to the administration of aflibercept every 2 months.3 In comparison, faricimab was administered 10 times when compared to similar results of aflibercept which was administered 15 times over the course of 2 years.3 This is a massive improvement in the quality of life of patients lessening the burden and risk of undergoing invasive intravitreal procedures.
Aside from the decreased risk of infections due to fewer on average needed doses of faricimab, TENAYA and LUCERNE were two studies aimed toward further establishing the drug's efficacy. Within these studies, the safety results were similar and without red flags. There were no cases of retinal vasculitis or intraocular inflammation associated with treatment.4
In contrast, one of the more recently released drugs, also anti-VEGF, Beovu, was found to have an increased risk of intraocular inflammation and retinal vasculitis.5 Due to these risk factors association, Beovu has since been removed from the market due to its less favorable profile. To date, Vabysmo has shown much promise in both its safety and efficacy when compared to competitor drugs.
Susvimo is the first port-delivery system (PDS) used to treat patients with wet AMD, and it was designed to reduce the treatment burden and improve overall outcomes. It contains Ranibizumab, which is a recombinant monoclonal antibody Fab-fragment against VEGF-A.9
It received FDA approval in 2021 after the ARCHWAY phase 3 study showed that Susvimo demonstrated noninferiority and equivalent efficacy compared to monthly Ranibizumab injections.10 Susvimo was approved for patients who had previous successful treatments with anti-VEGF intravitreal injections.10
Genentech and Roche voluntarily recalled Susvimo due to a defect in the implant seal.6 After exposure to repeating puncturing, the septum that keeps the medication from leaking out did not meet standards.6,7 As of August 2022, there have been 33 reported cases of septum dislodgement in approximately 1,419 patients with implants (2.3%, including reimplantations) and 5,236 refill-exchange procedures (0.63%) across PDS clinical trials.
The phase 4 study compares Susvimo versus Lucentis, with the primary outcome being BCVA and early treatment diabetic retinopathy study (ETDRS) changes.10 The study will also compare outcomes in corneal endothelial cell density.10 Of the 195 implants and 24 refill exchanges on the commercial side, there have been no reported implant dislodgement cases.10
For patients with Susvimo implants, the recommendations are to continue treatment as the benefit-risk has not been impacted. Careful refill exchanges and examination for septum dislodgment are advised. Both companies hope to put Susvimo out in the market after further testing to assure patient safety.
Susvimo aims to reduce the number of treatments with intravitreal injections; however, the port-delivery system is still costly. The first-year price is upwards of $17,000, separated into more than $9,000 for the first 6 months and then $8,000 for the first refill.12
Treatment for neovascularization and macular edema comes with a significant patient treatment burden. The goal of many intravitreal injections is to increase the treatment intervals.
Meanwhile, port-delivery systems can offer patients an improved treatment modality with a significantly decreased treatment burden.
- Mojumder NI, Khanani AM. The Mechanism of the Bispecific Antibody Faricimab. Retinalphysician.com. Retinal Physician. Published March 1, 2019. https://www.retinalphysician.com/issues/2019/march-2019/the-mechanism-of-the-bispecific-antibody-faricimab.
- Genentech. VABYSMO™ (Faricimab-Svoa) | Clinical Trial Efficacy in NAMD. Vabysmo.com. Genentech. https://www.vabysmo-hcp.com/namd-data/efficacy-in-namd.html.
- Seeking Alpha. New Two-Year Data Confirm Genentech's Vabysmo Improves Vision with Fewer Treatments for People with Wet Age-Related Macular Degeneration. Seeking Alpha. https://seekingalpha.com/pr/18866204-new-two-year-data-confirm-genentech-s-vabysmo-improves-vision-fewer-treatments-for-people-wet.
- Business Wire. New Two-Year Data Confirm Genentech's Vabysmo Improves Vision with Fewer Treatments for People with Wet Age-Related Macular Degeneration. Business Wire. Published July 14, 2022. https://www.businesswire.com/news/home/20220714005018/en/New-Two-Year-Data-Confirm-Genentech%E2%80%99s-Vabysmo-Improves-Vision-With-Fewer-Treatments-for-People-With-Wet-Age-Related-Macular-Degeneration.
- Monés J, Srivastava SK, Jaffe GJ, et al. Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion–Related Events with Brolucizumab. American Academy of Ophthalmology. Published November 15, 2020. https://www.aaojournal.org/article/S0161-6420(20)31075-7/fulltext.
- Singh RP, Khanani A. Genentech voluntarily recalls Susvimo ocular implant. Healio. Published October 18, 2022. Retrieved January 26, 2023. https://www.healio.com/news/ophthalmology/20221018/genentech-voluntarily-recalls-susvimo-ocular-implant.
- Freedman J. Subject: Voluntary recall of the SUSVIMOTM ocular implant. Published October 2022. Retrieved January 26, 2023. https://www.gene.com/download/pdf/Susvimo_DHCP_Important_Prescribing_Information_2022-10-18.pdf.
- Genentech. A study of the response to treatment after transition to the port delivery system with ranibizumab [Susvimo (ranibizumab injection)] in patients with neovascular age-related macular degeneration previously treated with Intravitreal agents other than ranibizumab. (n.d.). Retrieved January 26, 2023. https://clinicaltrials.gov/ct2/show/NCT04853251.
- Genentech. SUSVIMO (Ranibizumab Injection) a treatment option for WET AMD. susvimo.com. Retrieved January 26, 2023. https://www.susvimo.com/.
- Genentech. SUSVIMO prescribing information. (n.d.). Retrieved January 26, 2023. https://www.gene.com/download/pdf/susvimo_prescribing.pdf.
- Hoffman-La Roche. A phase III study to evaluate the port delivery system with ranibizumab compared with monthly ranibizumab injections in participants with wet age-related macular degeneration. Retrieved January 26, 2023. https://clinicaltrials.gov/ct2/show/results/NCT03677934?view=results.
- Retina Specialist. Retina update: Market forces may be gathering to exert price pressures on anti-VEGF Drugs. Retina-specialist.com. Published November 30, 2021. Retrieved January 27, 2023. https://www.retina-specialist.com/article/retina-update-market-forces-may-be-gathering-to-exert-price-pressures-on-antivegf-drugs.
- Kansteiner F. Roche recalls new eye therapy Susvimo on leakage fears, aims for market return 'within a year or so'. Fierce Pharma. Published October 18, 2022. Retrieved January 27, 2023. https://www.fiercepharma.com/manufacturing/roche-recalls-susvimo-implant-lucentis-leakage-fears-return-market-expected-within#:~:text=Roche%20has%20launched%20a%20voluntary%20recall%20of%20Susvimo%E2%80%94an%20implant,manufacturing%20problems%20with%20the%20device.