Oct. 27, 2021
Roche announced that the U.S. Food and Drug Administration (FDA) has approved Susvimo (ranibizumab injection) 100 mg/mL for intravitreal use via ocular implant for the treatment of people with neovascular or “wet” age-related macular degeneration (nAMD) who have previously responded to at least two anti-vascular endothelial growth factor (VEGF) injections, according a Roche press release.
Neovascular AMD is a potentially blinding condition that requires treatment with eye injections as often as once a month.1,2,3,4 Roche says Susvimo, previously called Port Delivery System with ranibizumab, is the first and only FDA-approved treatment for nAMD that offers as few as two treatments per year.5,6
“Susvimo represents a major advancement in the treatment of retinal disease and is an important new option for patients with wet AMD,” said Carl Regillo, M.D., Chief of Retina Service at Wills Eye Hospital in Philadelphia and an Archway study investigator. “With Susvimo, my patients now have an option that can help them maintain their vision as well as anti-VEGF injections, but on a more manageable twice-yearly treatment schedule.”
Susvimo delivers ranibizumab continuously, offering people living with nAMD an alternative to anti-VEGF eye injections needed as often as once a month.3,4,5 The implant is surgically inserted into the eye during a one-time, outpatient procedure and refilled every six months.5,6 If necessary, supplemental ranibizumab treatment can be given to the affected eye while the Susvimo implant is in place.5
“We believe that Susvimo can help people with nAMD preserve their vision while potentially alleviating the treatment burden associated with current standards of care,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Susvimo’s approval builds on Roche’s long-standing commitment to people living with vision-threatening conditions.”
The approval is based on positive results from the phase III Archway study primary analysis, which showed nAMD patients treated with Susvimo achieved and maintained vision gains equivalent to monthly ranibizumab injections – +0.2 and +0.5 eye chart letters from baseline, respectively – at weeks 36 and 40 of treatment. In addition, only 1.6 percent of Susvimo patients received supplemental ranibizumab treatment before their first refill, and more than 98 percent could go six months before their first refill.5
In the Archway study, Susvimo was generally well-tolerated, with a favorable benefit-risk profile. However, the Susvimo implant has been associated with a three-fold higher rate of endophthalmitis than monthly intravitreal injections of ranibizumab. Many of these events were associated with conjunctival retractions or erosions. Appropriate conjunctiva management and early detection with surgical repair of conjunctival retractions or erosions may reduce the risk of endophthalmitis.
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In clinical trials, 2.0 percent of patients receiving a ranibizumab implant experienced at least one episode of endophthalmitis. The most common adverse events (AEs) were conjunctival haemorrhage, conjunctival hyperaemia, iritis and eye pain.6 The safety profile of Susvimo in the clinical trial setting is well understood and will continue to be monitored closely.5
Roche has a robust phase III clinical development programme for Susvimo, including the Portal, Pagoda, Pavilion and Velodrome studies. Portal is an extension study evaluating the long-term safety and efficacy of Susvimo in nAMD.7
Pagoda is evaluating Susvimo for the treatment of people with diabetic macular edema (DME), while Pavilion is a study of Susvimo in diabetic retinopathy without DME.8,9 Velodrome is evaluating Susvimo refilled every nine months in nAMD.10 Susvimo is also currently under review for the treatment of nAMD by the European Medicines Agency (EMA).
Susvimo will be available in the U.S. in the coming months.
Roche’s late-stage ophthalmology portfolio also includes faricimab, a bispecific antibody under FDA and EMA review for the treatment of nAMD and DME. The FDA is additionally reviewing faricimab for the treatment of diabetic retinopathy.
About the Archway Study5,11,12
Archway (NCT03677934) was a randomised, multicentre, open-label phase III study evaluating the efficacy and safety of Susvimo (ranibizumab injection) 100 mg/mL for intravitreal use via ocular implant administered via the Susvimo eye implant, refilled every six months at fixed intervals, compared to monthly intravitreal injections of ranibizumab 0.5 mg in 415 people living with neovascular or “wet” age-related macular degeneration (nAMD). Patients enrolled in Archway were responders to prior treatment with anti-vascular endothelial growth factor (VEGF) therapy. In both study arms, patients were treated with at least three anti-VEGF injections within the six months prior to their Archway screening visit. The primary endpoint of the study was the change in best-corrected visual acuity (BCVA) score (the best distance vision a person can achieve – including with correction such as glasses – when reading letters on an eye chart) from baseline at the average of Week 36 and Week 40. Secondary endpoints include safety, overall change in vision (BCVA) from baseline and change from baseline in centre point thickness over time.
According to pre-specified study criteria, Susvimo was shown to be non-inferior and equivalent to monthly ranibizumab injections. On average, patients had received five prior ranibizumab injections before their first study treatment visit. In the Susvimo arm of the study, patients gained an average of 0.2 eye chart letters in visual acuity from baseline compared with 0.5 eye chart letters for the monthly ranibizumab arm. During the first treatment interval, before the first scheduled refill, 1.6 percent of Susvimo patients assessed (n=4/246) received supplemental ranibizumab treatment, and 98.4 percent of patients (n=242/246) did not receive supplemental treatment.
In the Archway study, Susvimo was generally well-tolerated, with a favourable benefit-risk profile. The safety profile of Susvimo in the clinical trial setting is well understood and will continue to be monitored closely.
 Pennington KL, DeAngelis MM. Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. Eye and Vision. 2016;3:34.
 Little K, et al. Myofibroblasts in macular fibrosis secondary to neovascular age-related macular degeneration-the potential sources and molecular cues for their recruitment and activation. EBioMedicine. 2018;38:283-91.
 Schmidt-Erfurth U, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014;121:193-201.
 Heier JS, et al. The Angiopoietin/Tie pathway in retinal vascular diseases: a review. Retina-J Ret Vit Dis. 2021;41:1-19.
 Holekamp N, Campochiaro P, et al. Archway Randomized Phase 3 Trial of the Port Delivery System With Ranibizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2021.
 FDA. Highlights of prescribing information, Susvimo. 2021
 ClinicalTrials.gov. Extension study for the port delivery system with ranibizumab (Portal) [Internet; cited October 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT03683251
 ClinicalTrials.gov. This study will evaluate the efficacy, safety, and pharmacokinetics of the port delivery system with ranibizumab in participants with diabetic macular edema compared with intravitreal ranibizumab (Pagoda) [Internet; cited October 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT04108156
 ClinicalTrials.gov. A multicenter, randomized study in participants with diabetic retinopathy without center-involved diabetic macular edema to evaluate the efficacy, safety, and pharmacokinetics of ranibizumab delivered via the port delivery system relative to the comparator arm (PAVILION) [Internet; cited October 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT04503551
 ClinicalTrials.gov. A study of the efficacy, safety, and pharmacokinetics of a 36-week refill regimen for the Port Delivery System with ranibizumab in patients with neovascular age-related macular degeneration (Velodrome) [Internet; cited October 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT04657289
 ClinicalTrials.gov. 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 (ARCHWAY) [Internet; cited October 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT03677934
 Regillo C, et al. Port delivery system with ranibizumab (PDS) for nAMD: Updated data from the Archway phase 3 trial. Angiogenesis, Exudation, and Degeneration 2021 Annual Meeting; 2021 February 12–13.
 Bright Focus Foundation. Age-Related Macular Degeneration: Facts & Figures. [Internet; cited October 2021]. Available from: https://www.brightfocus.org/macular/article/age-related-macular-facts-figures
 Wong WL ,et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. The Lancet Global Health. 2014;2:106-16.
 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;102:1691-95.
 FDA. Highlights of prescribing information, Lucentis. 2012 [Internet; cited October 2021]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125156s0069s0076lbl.pdf
 Khan M, et al. Targeting Angiopoietin in retinal vascular diseases: A literature review and summary of clinical trials involving faricimab. Cells. 2020;9:1869.