Last month the Food and Drug Administration approved our sixth treatment for neovascular age-related macular degeneration, expanding our management toolbox with a truly differentiated option.
There is no question that more durable treatment options are needed. Repeatedly, data from patients with neovascular AMD managed with anti-VEGF therapy in routine clinical practice around the world have indicated that real-world outcomes fall far short of those achieved in prospective clinical trials with consistent monitoring and dosing.
Susvimo (Genentech/Roche), originally known as the Port Delivery System (PDS), filled with a 100-mg/mL solution of ranibizumab, is an attractive solution to our durability challenge. In particular, while the Phase III trial employed a refill interval of every six months, the median time to first refill was 15 months in the Phase II LADDER trial, suggesting that most patients may be able to be extended substantially longer.
PDS development is a phenomenal case study of the challenges and opportunities of innovation. Originally conceived by the intriguing Eugene de Juan, MD, the concept was eventually acquired by Genentech. The program was nearly halted in early phase trials because of a high incidence of vitreous hemorrhage. Following modifications to the surgical technique, this adverse event was effectively abolished.
The surgical technique has continued to evolve during the ongoing Phase III trials. In particular, a tremendous amount of attention is now given to proper conjunctival and Tenon’s capsule manipulation.
But, everything carries a risk/benefit ratio. Repeated intravitreal injections have proven remarkably safe over the last 15 years. The so-called black box warning in the Susvimo package insert regarding a 2 percent rate of endophthalmitis among patients followed for a median of two years is worth noting. Other risks associated with the surgical procedure itself and with permanent residence of a foreign body attached to the eye wall have been described. Importantly, however, most of these risks appear to be minimized with meticulous attention to surgical detail, highlighting the importance of training before using the product for the first time.
We must consider all these issues along with longer-term follow-up and the impressive patient preference data reported to date as we discern where the PDS will fit into our management recommendations.
It’s an exciting time in retina. With multiple additional pharmacotherapies, including KSI-301 (Kodiak Sciences), an anti-VEGF biopolymer conjugate and OPT-302 (Opthea), which targets VEGF C and D, in Phase III trials, as well as faricimab (Genentech/Roche) awaiting possible FDA approval, our toolbox appears ready to expand further. RS