Roche's Susvimo Receives FDA Approval: A Paradigm Shift in nAMD Treatment with Only Two Annual Doses

On October 22, Roche announced that the FDA has approved its novel drug delivery system, Susvimo (ranibizumab injection 100 mg/mL), for the treatment of patients with neovascular (wet) age-related macular degeneration (nAMD) who have previously responded to at least two anti-VEGF therapies.

Susvimo, also known as the ranibizumab Port Delivery System (Port Delivery System with ranibizumab), is a rice-grain-sized ocular implant device that is surgically implanted into the eye in a single procedure. It provides sustained intraocular release of ranibizumab and requires only an outpatient refill every six months, thereby changing the treatment regimen for nAMD patients from the conventional once-monthly injections.

nAMD is one of the common causes of central vision loss in humans, affecting approximately 20 million people worldwide and serving as a leading cause of blindness in individuals aged 60 and above. The pathology of nAMD is characterized by the uncontrolled growth of new and abnormal blood vessels beneath the macula, leading to edema, hemorrhage, and/or fibrosis, which results in rapid and severe vision loss. Therefore, intravitreal injection of anti-VEGF agents is also a primary clinical treatment for wAMD.

Anti-VEGF drugs have been developed for the treatment of nAMD for 15 years. The primary focus of technological advancement has been to reduce the frequency of intravitreal injections, alleviate psychological anxiety and safety risks, and improve treatment adherence. For example, aflibercept is an Fc fusion protein that binds to all isoforms of VEGF-A, maintaining long-term intraocular anti-VEGF activity and enabling a dosing interval of once every two months. Beovu (brolucizumab), developed by Novartis, is a single-chain antibody fragment (scFv) with enhanced tissue penetration. It permits administration at a higher molar dose, thereby increasing drug distribution at the lesion site, and represents the first anti-VEGF therapy requiring injections only once every three months.

Susvimo is the first FDA-approved novel therapy to reduce the frequency of intravitreal injections for nAMD patients to twice a year, marking a major paradigm shift in the clinical treatment of nAMD over the past 15 years.

In the Phase III Archway study, which served as the basis for approval, visual acuity at weeks 36 and 40 improved by 0.2 and 0.5 from baseline, respectively, in patients receiving the Susvimo implant, demonstrating efficacy comparable to monthly ranibizumab injections. Furthermore, only 1.6% of patients in the Susvimo treatment group required supplemental ranibizumab therapy during the first treatment cycle (first refill), with over 98% of patients not requiring additional treatment.

Regarding safety, the most common adverse events in patients receiving Susvimo were conjunctival hemorrhage, conjunctival hyperemia, iritis, and ocular pain. 2.0% of patients experienced at least one episode of endophthalmitis, which is more than three times the rate observed with monthly intravitreal ranibizumab injections. Most cases were associated with conjunctival atrophy and erosion. Therefore, conjunctival health management should be emphasized; early detection of conjunctival atrophy and erosion enables surgical repair, thereby reducing the risk of endophthalmitis. Overall, Susvimo is well tolerated and demonstrates an acceptable risk-benefit profile.

Beyond improving the treatment experience of anti-VEGF therapy, the standard of care for nAMD, Roche is also pursuing breakthroughs in drug mechanisms. This is because VEGF is not the sole pathway involved in the pathogenesis and progression of this complex disease. Faricimab, developed by Roche, is a bispecific antibody that inhibits abnormal neovascularization by targeting two distinct pathways: angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A).

Mechanistically, VEGF-A and Ang-2 signaling destabilize blood vessels, induce neovascularization, and promote inflammation. While effectively controlling neovascularization by blocking VEGF/VEGFR signaling, faricimab also inhibits Ang-2 signaling to enhance vascular stability and mitigate retinal inflammation. Compared with anti-VEGF monotherapy, its use in treating various retinal diseases reduces the frequency of intravitreal injections and improves patients' long-term visual outcomes.

Faricimab is the first bispecific antibody developed for ophthalmic diseases, designed for a dosing regimen of one injection every four months. Marketing applications for the treatment of nAMD and DME have been submitted, with approval expected in 2022.