Highlights

Susvimo (ranibizumab) is a new drug indicated to treat neovascular (wet) age-related macular degeneration in patients who have previously responded to at least two intravitreal VEGF inhibitor injections.

Age-related macular degeneration (AMD), also known as age-related maculopathy (ARM), is a progressive chronic disease of the retina, which, along with cataract, open-angle glaucoma, and diabetic retinopathy (diabetic eye disease), is the leading cause of vision loss and affects most people over the age of 50. The pathology is characterized by drusen (focal yellowish deposits of extracellular matrix), geographic atrophy of retinal pigment epithelium, and growth of new blood vessels. Treatment varies depending on the type of age-related macular dystrophy, which may be dry (atrophic, non-exudative) and wet (neovascular, exudative).

The treatment of wet age-related macular degeneration involves intravitreal injections (into the vitreous body) of vascular endothelial growth factor (VEGF) inhibitors. These drugs include Eylea (aflibercept) by Regeneron Pharmaceuticals and Bayer, Lucentis (ranibizumab) by Roche and Novartis, Beovu (brolucizumab) by Novartis, and the newest Vabysmo (faricimab) by Roche. The anticancer Avastin (bevacizumab) by Roche is used off-label.

The key difference between Susvimo and all other existing VEGF inhibitors on the market lies in its implementation. The new product is made in the form of an implant that is inserted once into the eye surgically in an outpatient setting and is then refilled with the drug every six months. Competitive options involve intravitreal injections much more frequently, which, first, is very inconvenient for the patient and, second, is still a traumatic procedure for the eyes. For example, Vabysmo is injected every 2–4 months, Beovu every 2–3 months, Eylea every 2 months, and Lucentis once a month.

Susvimo, developed by Roche’s Genentech, is approved by the U.S. Food and Drug Administration (FDA) in late October 2021.

For U.S. patients, installing a filled Susvimo will cost $17,250 for the first year, while each subsequent refill will cost $8,000. The estimated final cost turns out to be a quarter lower compared to the annual course of Lucentis.

Susvimo (ranibizumab).

 

Susvimo: Mechanism of Action of Ranibizumab

The mechanism of action of Susvimo is similar to that of Lucentis.

The active ingredient of Susvimo is ranibizumab, a fragment of a recombinant humanized IgG1 kappa isotype monoclonal antibody of the kappa isotype for intraocular use, which inhibits the biological activity of vascular endothelial growth factor A (VEGF-A).

Ranibizumab binds to the receptor-binding site of multiple biologically active forms of VEGF-A, including VEGF110, VEGF121, VEGF165. VEGF-A has been found to induce neovascularization and transudation in models of ocular angiogenesis and vascular occlusion and is thought to contribute to the pathophysiology of wet age-related macular degeneration. Binding of ranibizumab to VEGF-A prevents the latter from interacting with its VEGFR1 and VEGFR2 receptors on the surface of endothelial cells, resulting in inhibition of endothelial cell proliferation, transudation, and new blood vessel formation.

The Susvimo implant, formerly called the Port Delivery System (PDS) with ranibizumab, being the size of a grain of rice and containing 2 mg of ranibizumab solution, ensures its continuous release into the vitreous body with a half-life of approximately 25 weeks. The serum concentration of ranibizumab at the 24-week treatment interval is maintained below the maximum and above the minimum concentration observed with monthly administration of 0.5 mg intravitreal injections of Lucentis.

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The efficacy and safety of Susvimo were evaluated in the Archway (NCT03677934) phase 3 (randomized, single-blinded, active-controlled, multicenter) clinical trial involving adult (50 years and older) patients (n=415) with exudative neovascular age-related macular degeneration diagnosed within 9 months before screening.

Among the key requirements for inclusion in the trial: at least 3 intravitreal injections of a VEGF inhibitor in the 6 months prior to screening; demonstrated response to anti-VEGF therapy; and a Best-Corrected Visual Acuity (BCVA) of 34 letters or better.

Participants were treated with either the Susvimo implant, which was refilled every 6 months, or with intravitreal Lucentis injections every month.

Importantly, the Susvimo group was allowed to receive up to 8 additional Lucentis injections if there was a therapeutic need. This was encountered by 1.6% of patients in the first 24 weeks of the study and 5.4% in the following 24 weeks.

The primary endpoint of treatment efficacy was the change in BCVA, which was assessed by averaging at weeks 36 and 40.

The primary endpoint of treatment efficacy was the change in Best-Corrected Visual Acuity (BCVA) averaged over 48, 52, and 56 weeks of therapy, according to the Early Treatment Diabetic Retinopathy Study (ETDRS) letter chart.

The Susvimo group demonstrated no worse efficacy in the treatment of wet age-related macular degeneration compared to Lucentis administration when it comes to change and maintenance of BCVA on the Early Treatment Diabetic Retinopathy Study (ETDRS) letter chart.

The safety profile of Susvimo is characterized by an acceptable benefit to risk ratio. However, prescribing information of the Susvimo implant comes with a black-boxed warning stating a threefold increased incidence of endophthalmitis when compared to monthly intravitreal injections of Lucentis. Many cases of endophthalmitis were associated with conjunctival retraction or conjunctival erosion. Early surgical correction of the latter contributed to reducing the risk of endophthalmitis. Nevertheless, endophthalmitis was diagnosed in 2.0% of patients who underwent the Susvimo procedure.

 

Extras

Susvimo (ranibizumab). Prescribing information. U.S. [PDF]

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Julia Mardi

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Julia strives to recognize in advance in which direction the pharmaceutical industry is moving. Her professional interests include gene therapy, immune checkpoint inhibitors, molecular biology, and drug repurposing.

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