The arrival of Susvimo, an ocular implant for treatment of macular degeneration, poses a challenge for ophthalmic reference products and biosimilars.
Has Roche developed a viable defense against ranibizumab biosimilar competition for Lucentis, the company’s product for neovascular age-related macular degeneration (wet AMD)?
The FDA’s approval last week of Roche’s ranibizumab implant (Susvimo) offers patients convenience as well as an alternative to monthly injections.
Until now, ranibizumab administration has involved eye injections as often as monthly. Susvimo is implanted in the eye and contains a reservoir of ranibizumab good for 6 months. For patients looking at 12 monthly treatments vs just a Susvimo implant and refill over the span of a year, the latter may seem the better way to go.
And the significance for biosimilar competition could be meaningful. Just in September 2021, Samsung Bioepis and Biogen’s ranibizumab (Byooviz) became the first ranibizumab biosimilar to gain FDA approval, and the companies do not plan for commercialization of their product before June 2022, owing to a licensing agreement with Roche.
This would allow Susvimo a chance to become established in the marketplace, and before patients are ever offered monthly injections of biosimilar ranibizumab, many may be well accustomed to the twice-yearly treatments with Susvimo.
Their willingness to switch to potentially more-affordable biosimilars on a monthly injection regimen will be put to the test.
Although Byooviz is the only ranibizumab biosimilar with FDA approval, there are several more in the pipeline. These include Xlucane, an Xlucane/Bausch biosimilar candidate in phase 3 trials; LUBT010, a Lupin product candidate also in phase 3; and FYB201, from Coherus BioSciences and Bioeq. A biologics license application for FYB201 has been accepted for review by the FDA. So, with a new method of administration entering the marketplace, there is much at stake for these companies.
Coherus BioSciences and Bioeq are anticipating action by the FDA on August 2, 2022, and if the biosimilar is approved, they plan to launch in the United States in the second half of that year.
The Susvimo impact may also reach beyond ranibizumab to other treatments commonly used for the treatment of macular degeneration. Aflibercept (Eylea) also is injected monthly for treatment of these conditions, and bevacizumab (Avastin) is used off-label in the same way.
There are as many as 8 aflibercept biosimilars under development, many of them in phase III development; however, there has been pushback from the ophthalmology community about the use of bevacizumab biosimilars for eye conditions.
Susvimo delivers ranibizumab into the eye continuously, and while Roche doesn’t guarantee that patients will need just 2 treatments (refills per year), the company boasts that Susvimo has that potential. The product is indicated for patients who have previously responded to at least 2 anti–vascular endothelial growth factor (VEGF) injections.
“A Major Advancement”
“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, MD, chief of Retina Service at Wills Eye Hospital in Philadelphia and an investigator in the pivotal phase III Archway study that led to the product’s approval.
“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,” he said.
The Archway study demonstrated that patients with wet AMD treated with Susvimo achieved and maintained vision gains equivalent to those achieved with monthly ranibizumab eye injections. That equivalency was defined as gains of 0.2 to 0.5 eye chart letters from baseline by weeks 36 and 40 of treatment, respectively.
Roche said that only a small percentage (1.6%) of patients receiving Susvimo needed supplemental ranibizumab treatment prior to the first scheduled refill at 6 months.
The Fine Print
Despite the convenience, some patients may prefer to stick with monthly ocular injections. Investigators reported a “3-fold higher rate” of endophthalmitis with Susvimo than with monthly injections. Endophthalmitis is an infection inside the eye and is considered a medical emergency. “In clinical trials, 2.0% of patients receiving a ranibizumab implant experienced at least 1 episode of endophthalmitis,” authors of the study reported.
A December 2008 study of the incidence of endophthalmitis related to intravitreal injections of bevacizumab and ranibizumab noted an overall rate of endophthalmitis of .02%, or an incidence of 1 in 4500 injections, based on a study of 12,585 injections of intravitreal bevacizumab and 14,320 injections of intravitreal ranibizumab.
The most common adverse events associated with Susvimo in Archway were conjunctival hemorrhage, conjunctival hyperaemia, iritis, and eye pain. “The safety profile of Susvimo in the clinical trial setting is well understood and will continue to be monitored closely,” Roche said.
The company has further trials of this product under way, including the Velodrome study, which is evaluating Susvimo refilled every 9 months (instead of 6) in wet AMD. The studies will elucidate the value of Susvimo for treatment of diabetic macular edema and diabetic retinopathy.
Roche intends to launch the product “in the coming months.”
The Center for Biosimilars® interviewed George Williams, MD, clinical spokesman for the American Academy of Ophthalmology, about the ranibizumab biosimilar approval and about the bevacizumab biosimilar intravitreal controversy.