Izervay significantly slows progression of geographic atrophy.
Until recently, you could give your patients with geographic atrophy (GA) compassion and caring, but little hope that you could impact the progression of this devastating disease.
“We had no interventions that could change the trajectory of what was happening to these patients and specifically to the central vision in these patients,” says Veeral S. Sheth, MD, MBA, FASRS, FACS, director of clinical research, University Retina and Macula Associates, clinical assistant professor, University of Illinois at Chicago. “It’s been a huge unmet need for a long time.”
With the August 2023 FDA approval of Izervay (avacincaptad pegol intravitreal solution) (Iveric Bio and Astellas Company), patients have a new reason for optimism. Patients with GA will suffer terrible consequences: for instance, 67% of people who have GA in both eyes lose the ability to drive in a little over a year and a half, according to Iveric Bio. And, in 2 years, 50% of people with GA lose two lines of vision, the company notes.
What is Izervay?
A complement C5 inhibitor, Izervay is approved for the treatment of GA secondary to AMD. This monthly injection, according to Astellas, is the only approved GA treatment with a statistically significant reduction in the rate of GA progression at the 12-month primary endpoint across two Phase 3 clinical trials, known as GATHER1 and GATHER2. GATHER1 was a Phase 2/3 trial. The recommended dose for Izervay is 2 mg (0.1 mL of 20 mg/mL solution) administered by intravitreal injection to each affected eye once monthly for up to 12 months.
Astellas also announced topline results of the GATHER2 trial in which the monthly dosing regimen met the primary objective to significantly slow GA growth compared to sham at 24 months. The treatment effect with the every-other-month dosing regimen for Izervay showed a similar reduction in the rate of GA growth compared to monthly dosing.
To be clear, Izervay does not cure GA, and patients will continue to lose vision. “We don’t have a way to cure this problem or reverse the damage that’s been done,” notes Dr. Sheth.
“The goal of these treatments is to slow progression of GA,” adds Carl Danzig, MD, director, vitreoretinal services and retina clinical research, Rand Eye Institute, Deerfield Beach, Fla. and affiliate assistant professor, Florida Atlantic University. “Its goal is to decrease the rate of GA progression, which can hopefully delay vision loss or preserve vision as long as possible.”
In the GATHER1 and GATHER2 studies, in the first year of the trials, GA progression slowed by up to 35%, according to Dhaval Desai, PharmD, senior vice president and chief development officer, Iveric Bio and Astellas Company. The rate of slowing, he notes, varies highly from patient to patient. Dr. Sheth generally tells patients that the injections can slow the disease by 20% to 30%.
Arshad M. Khanani, MD, MA, FASRS, director of clinical research at Sierra Eye Associates and clinical associate professor at the University of Nevada, Reno School of Medicine, is offering Izervay to all of his GA patients, noting that the ideal patient is one with non-foveal lesions. It’s important, he says, to set the expectation with patients that Izervay will not stop or reverse GA but rather slow its progression. Treatment with Izervay,
Dr. Khanani notes, may result in slowing catastrophic vision loss and longer maintenance of vision. Slowing GA will preserve retinal tissue for longer and allow patients to have better quality of life for longer, he says.
Izervay’s mechanism of action involves targeting complement C5. Inhibiting C5, notes Astellas, preserves upstream benefits of C3 and may prevent the formation of the membrane attack complex (MAC), which initiates retinal cell death.
“The complement cascade, when it’s upregulated, can cause significant inflammation in the retina,” Dr. Sheth says. “We’re finally able to target these pathways that have gone awry in a way where we can better control the inflammation that would otherwise destroy retinal tissue.”
“Complement has had probably the strongest evidence in the development and progression of GA,” Dr. Desai adds. “Also, it is the only mechanism that has been tested in GA that has given us positive outcomes in terms of slowing disease.”
C5, notes Dr. Desai, is the terminal part of the complement pathway. “By hitting that terminal pathway, we’re affecting those things that cause the damage, but we’re maintaining the normal homeostatic mechanism for the rest of the complement pathway,” he says.
Those interviewed say you can expect your GA patients to tolerate Izervay. The drug “has a consistent safety profile from year one to year two, meaning there’s a very low rate of inflammation,” notes Dr. Desai. “There’s a very low rate of endophthalmitis and ischemic optic neuropathy.”
“In the GATHER trials, the safety profile was very favorable,” agrees Dr. Danzig. “We’re hopeful in the real world that will carry through also.”
The most common adverse reactions reported in patients receiving Izervay were conjunctival hemorrhage, increased IOP, blurred vision and neovascular AMD, according to Astellas.
Finally, cause for hope
Izervay, Dr. Danzig explains, not only gives patients hope that they can preserve their vision longer, but also offers them encouragement in that they see innovation in this field. “They see that the ball is moving forward and that their potentially blinding condition is now being addressed.” OM
Dr. Danzig is a consultant for Iveric Bio. Dr. Khanani is a consultant for Iveric Bio and receives research funding from Iveric Bio. Dr. Sheth is a consultant for Iveric Bio.