Despite holding the lead with its complement inhibitor Syfovre, Apellis Pharmaceuticals is discovering that the geographic atrophy market is a tough nut to crack.

Syfovre—which became the first medication specifically approved by the FDA for geographic atrophy (GA) in early 2023—posted U.S. sales of $130.2 million during the first three months of 2025, down 22% quarter over quarter and 3% versus the same period in 2024.

Despite increases in patient demand in recent months, Syfovre's revenue totals have suffered from funding shortfalls at copay assistance programs and inventory fluctuations, Apellis CEO Cedric Francois, M.D., Ph.D., said in a statement.

Syfovre’s sales performance in the quarter fell well below Mizuho Securities’ forecast of $157 million, with analysts at the firm stating the miss was “worse than we could have envisioned.”

Taking various challenges into account—from safety questions and stalling class growth to copay assistance struggles—the Mizuho team now envisions “persistent challenges for Syfovre’s uptake” in both the short- and long-term.

Although Apellis executives had previously suggested that seasonality and inventory issues affecting Syfovre in the first quarter were one-off factors, the company noted on its earnings call last week that it now expects the fallout of underfunded copay assistance programs to bleed into the rest of the year.

Apellis didn't get into details about the copay funding shortfall, but online sourcesindicate that there have been major disruptions in the ophthalmology space amid funding challenges for such programs.

Underfunding of copay assistance programs—which Regeneron’s CEO also lamented on his company’s earnings call last month—has forced Apellis to give away more Syfovre samples. The company now figures that its current sampling rate of roughly 10,000 vials per quarter will become the norm, versus a previous rate of around 5,000 vials per quarter, analysts at Evercore ISI wrote in a recent note to clients.

While Apellis could scale that number back, it’s “not clear when that could happen,” the Evercore team said.

In turn, the Mizuho team has dialed back its overall expectations for the drug, now predicting Syfovre will hit an annual sales peak of $1.08 billion in 2033. Mizuho’s trimmed forecast stands 16% below the current consensus estimate for peak Syfovre sales of $1.29 billion in 2033.

Overall, Apellis delivered $166.8 million in total sales for the first quarter, down roughly 3% compared to the same three-month stretch in 2024. Even as Syfovre took a hit, the company’s other commercial product, Empaveli, struggled too, though the drug still has room to recover, the Mizuho team said.

Empaveli, which is underpinned by the same molecule, pegcetacoplan, as its sibling Syfovre, pulled down $19.7 million in first-quarter sales. That revenue haul was down 23% year over year and failed to meet Mizuho’s forecasted $24 million for the period.

Nevertheless, the “spotlight shifts to Empaveli” now that Syfovre faces several challenges, the Mizuho team said.

In August, Empaveli is up for an FDA approval verdict in two rare kidney indications—complement 3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN)—that affect roughly 5,000 patients in the United States and 8,000 in Europe, the Mizuho analysts noted.

Mizuho further predicts Empaveli will hit peak sales of roughly $350 million in C3G/IC-MPGN, should it win approval.

Apellis’ Syfovre struggles—and those facing the GA market more broadly—aren’t new, though the drug’s latest sales miss is much more acutely felt than the stagnation it endured in previous quarters.

Meanwhile, Astellas’ Izervay is experiencing growing pains, too, with the Japanese drugmaker in February reporting that sales growth had slowed to just 4% in the last three months of 2024, despite the drug being early in its launch. Izervay debuted roughly six months after Syfovre’s launch in 2023.

Still, Apellis’ top brass appears confident in their ability to unlock the GA market, at least for now.

“We are still in the early phases of growth and estimate that only half of diagnosed GA patients are seen by an eyecare professional. Of those, less than 10% are receiving treatment,” Apellis’ CEO Francois said in late February. “Building a new market takes time.”