Until the approval of Apellis’ Syfovre earlier this year, there was no treatment for geographic atrophy. Shortly after, Astellas’ Izervay was also approved for the eye condition. Now, as the only two companies with approved geographic atrophy treatments, there appears to be an ongoing rivalry between them to see who can come out on top in the battle for the geographic atrophy crown.
Geographic atrophy is an advanced form of dry age-related macular degeneration. The disease is progressive and irreversible caused by the growth of lesions, which destroy the retinal cells responsible for vision. The vision loss caused by geographic atrophy – which often affects both eyes – severely impairs independence and quality of life by making it difficult to participate in daily activities.
In this article, we take a look at the events surrounding the historical approvals of the first two geographic atrophy treatments, and the ensuing rivalry between Apellis’ Syfovre and Astellas’ Izervay.
Apellis’ Syfovre becomes first approved geographic atrophy drug
In a milestone achievement, February 2023 saw the much anticipated U.S. Food and Drug Administration (FDA) approval of the first ever treatment for geographic atrophy. The therapy is called Syfovre and works by targeting C3, meaning it is designed to provide comprehensive control of the complement cascade.
“The approval of SYFOVRE is the most important event in retinal ophthalmology in more than a decade,” said Eleonora Lad, in the initial press release, who was the lead investigator for the phase 3 OAKS study of Syfovre. “Until now, there have been no approved therapies to offer people living with geographic atrophy as their vision relentlessly declined. With Syfovre, we finally have a safe and effective geographic atrophy treatment for this devastating disease, with increasing effects over time.”
Syfovre was approved based on positive results from the phase 3 OAKS and DERBY studies, for geographic atrophy patients with or without subfoveal involvement. In these studies, Syfovre was found to have reduced the rate of geographic atrophy lesion growth compared to sham, and demonstrated increasing treatment effects over time, with the greatest benefit (up to 36% reduction in lesion growth with monthly treatment in DERBY) occurring between months 18 to 24.
Astellas buys Iveric Bio for $5.9 billion
Following on from the approval of Syfovre, Astellas entered into an agreement to acquire Iveric Bio in May for $5.9 billion. This is where the competition between Astellas and Apellis really began; Iveric was involved in the discovery and development of novel treatments in the ophthalmic field and had been developing a treatment for geographic atrophy. In the same month that the FDA approved Syfovre, the administration also accepted for filing a new drug application (NDA) for Iveric’s geographic atrophy therapy, granting it priority review.
In Astellas’ press release about the acquisition agreement, it said that the acquisition of Iveric provided the company with a foundation of ophthalmology focused capabilities, including a multi-faceted commercial team, expansive network of experts in the ophthalmology field, established relationships with medical institutions, and the infrastructure and experience to drive its combined ophthalmology business going forward.
The acquisition was completed in July.
Apellis’ Syfovre sparks fears of severe side effect
Back when Syfovre was approved, the press release by Apellis stated: “The safety profile of Syfovre is well-demonstrated following ~12,000 injections. The most common adverse reactions (≥ 5%) reported in patients receiving Syfovre were ocular discomfort, neovascular AMD, vitreous floaters, and conjunctival hemorrhage.”
But, very shortly after Astellas completed the acquisition of Iveric, Apellis received some bad news about the possible side effects of Syfovre that temporarily set the company back in the geographic atrophy race. According to a report from BioPharma Dive, experts issued a letter to doctors flagging cases of eye inflammation associated with the drug, including six cases of occlusive retinal vasculitis – a rare but potentially blinding type of inflammation that blocks blood flow through the vessels that feed the retina and can cause blindness.
As the news broke, Apellis shares fell from over $84 to about $67 apiece.
In a statement to BioPharma Dive, Apellis said the real-world safety profile of its drug is “consistent with clinical studies” and that the events of intraocular inflammation with retinal vasculitis have occurred at an estimated rate of 0.01% per injection.
Additionally, the BioPharma Drive report said that Evercore ISI analysts Umer Raffat and Jon Miller stated in a note to clients that there was not a consensus on all six instances of retinal vasculitis, and noted how the findings had not been peer-reviewed. They said that one of the six patients had significant vision loss, while the outcomes of the others “may not be as significant.”
However, according to Spherix Global Insights, this did not stop Syfovre’s first-to-market edge from being diminished by the reports of its potentially severe side effects. Spherix wrote: “Nearly all surveyed physicians reported at least moderate impact on their future prescribing of Syfovre, with two-thirds suggesting the event will have significant impact on future prescribing of the treatment.”
In an update in early October, Apellis said that it had confirmed 10 cases of retinal vasculitis events.
Astellas receives FDA nod for Izervay
After the bad news for Apellis about Syfovre side effects, things were about to get worse for the company, as Astellas received FDA approval in August for their acquired geographic atrophy candidate, Izervay.
In the press release, it was announced that Izervay – a C5 inhibitor – became the only approved geographic atrophy treatment with a statistically significant reduction in the rate of geographic atrophy progression at the 12-month primary endpoint across two phase 3 trials – GATHER1 and GATHER2.
The FDA approval was based on these trials, which evaluated the safety and efficacy of monthly 2mg intravitreal administration of Izervay in patients with geographic atrophy secondary to age-related macular degeneration. As well as showing a statistically significant reduction in the rate of geographic atrophy growth, slowing of disease progression was observed as early as six months with up to a 35% reduction in the first year of treatment.
In Astellas’ press release, Arshad M. Khanani, director of clinical research at Sierra Eye Associates, Reno, Nevada, said: “Geographic atrophy has a devastating impact on patients’ lives and can lead to irreversible vision loss. As a C5 inhibitor, Izervay has shown to slow geographic atrophy progression by targeting the source of retinal cell death, and may preserve the upstream benefits of the complement system. The FDA approval of Izervay is great news for the retina community and our patients suffering from geographic atrophy.”
Rivalry heats up: Apellis and Astellas both put up trial data
In the latest reports concerning the rivalry between Apellis and Astellas, both companies rolled out additional data on Syfovre and Izervay, respectively, during presentations at this year’s meeting of the American Academy of Ophthalmology (AAO) in San Francisco.
Apellis shared data from its GALE extension study, saying that Syfovre yielded increasing treatment effects year over year, and helped patients achieve more than a 40% reduction in non-subfoveal lesion growth at the study’s three-year mark. Apellis’ Sfovre results also showed that the drug reduced general geographic atrophy lesion growth by 35% and 24% when given monthly or every other month, respectively, compared to placebo.
Meanwhile, Astellas shared data from its two-year GATHER2 study of Izervay, where investigators said they started to see the drug’s treatment benefit in as early as six months, and the drug’s effect more than doubled from year one to two. Ultimately, Astellas’ Izervay met its primary objective by delivering a statistically significant year-over-year reduction of 14% in the mean rate of geographic atrophy lesion growth. It also resulted in a 19% reduction in the mean rate of geographic atrophy lesion growth when given every other month in year two after monthly dosing during year one.
Apellis’ Syfovre vs Astellas’ Izervay: who will come out on top?
The rivalry between Astellas and Apellis has certainly been a hot topic recently. But, as to who will actually come out on top, it is very difficult to say at the moment, as both companies’ geographic atrophy treatments have data that could potentially set them back.
Although Astellas’ Izervay met its primary objective, the drug failed a prespecified objective looking at its ability to reduce vision loss. Meanwhile, side effects are also a key factor to look out for, in the battle between the two, and given Apellis’ Syfovre’s occlusive retinal vasculitis scare, this could work against it.
But, despite the side effect issue, recent shipping patterns do suggest that doctors appear to be moving on from the vasculitis scare in July. This is according to analysts in a note to clients last month, as reported by Fierce Biotech. If this is true, this could swing the pendulum in Apellis’ favor.
In terms of revenue, Apellis said that, during the third quarter of 2023, it expects approximately $74 million in preliminary U.S. net product revenue for Syfovre, while Astellas has reported around $8 million in early sales from Izervay – which we must remember was approved a few months after Syfovre.
There is likely to be more to follow in the coming months regarding the geographic atrophy treatment battle between these two companies and, ultimately, only time will tell who wins the crown.