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).

Recent Advancements in the Treatment of Wet 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.

Update on treatments for wet age-related macular degeneration

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) and its effectiveness

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.

TENAYA and LUCERNE studies

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.

What is Susvimo?

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

Voluntary recall of Susvimo

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

In conclusion

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.
  1. Mojumder NI, Khanani AM. The Mechanism of the Bispecific Antibody Faricimab. Retinal Physician. Published March 1, 2019.
  2. Genentech. VABYSMO™ (Faricimab-Svoa) | Clinical Trial Efficacy in NAMD. Genentech.
  3. 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.
  4. 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.
  5. 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.
  6. Singh RP, Khanani A. Genentech voluntarily recalls Susvimo ocular implant. Healio. Published October 18, 2022. Retrieved January 26, 2023.
  7. Freedman J. Subject: Voluntary recall of the SUSVIMOTM ocular implant. Published October 2022. Retrieved January 26, 2023.
  8. 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.
  9. Genentech. SUSVIMO (Ranibizumab Injection) a treatment option for WET AMD. Retrieved January 26, 2023.
  10. Genentech. SUSVIMO prescribing information. (n.d.). Retrieved January 26, 2023.
  11. 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.
  12. Retina Specialist. Retina update: Market forces may be gathering to exert price pressures on anti-VEGF Drugs. Published November 30, 2021. Retrieved January 27, 2023.
  13. 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.,manufacturing%20problems%20with%20the%20device.
Mark Shokralla, BA
About Mark Shokralla, BA

Mark Shokralla, BA, is a third-year medical student at William Carey University College of Osteopathic Medicine. He graduated in 2019 with a BA in Biology from the University of North Texas.

Mark Shokralla, BA
Sergio Karageuzian, BS
About Sergio Karageuzian, BS

Sergio Karageuzian, BS, is a third-year medical student at A.T. Still University School of Osteopathic Medicine in Arizona. In 2018, he graduated from the University of California, Davis with a B.S. in Microbiology.

Sergio Karageuzian, BS
Harris Ahmed DO, MPH
About Harris Ahmed DO, MPH

Harris Ahmed DO, MPH is a resident physician in ophthalmology at the Loma Linda University Eye Institute. He is a leader in health policy, serving in national leadership positions in multiple organizations including the AMA, AOCOOHNS, and AOA and has authored many publications and given lectures on public health advocacy and health policy, specializing in topics such as scope of practice, physician distribution, and medical education.

Harris Ahmed DO, MPH
David RP Almeida, MD, MBA, PhD
About David RP Almeida, MD, MBA, PhD

David Almeida MD MBA PhD is a vitreoretinal eye surgeon offering a unique voice that combines a passion for ophthalmology, vision for business innovation, and expertise in ophthalmic and biomedical research. He is part of Erie Retinal Surgery, a retina-only private practice with an esteemed reputation for excellence in Pennsylvania. Dr. Almeida and Erie Retinal Surgery diagnose and treat all medical and surgical conditions of the vitreous, retina and macula.

David RP Almeida, MD, MBA, PhD
Eric K Chin, MD
About Eric K Chin, MD

Dr. Eric K Chin is a board-certified ophthalmologist in the Inland Empire of Southern California. He is a partner at Retina Consultants of Southern California, and an Assistant Professor at Loma Linda University and the Veterans Affair (VA) Hospital of Loma Linda. He is a graduate of University of California Berkeley with a bachelor’s of science degree in Bioengineering. Dr. Chin received his medical degree from the Chicago Medical School, completed his ophthalmology residency at the University of California Davis, and his surgical vitreoretinal fellowship at the University of Iowa. During his residency and fellowship, he was awarded several accolades for his teaching and research in imaging and novel treatments for various retinal diseases.

Eric K Chin, MD
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