Regeneron's Eylea has long dominated the ophthalmology market thanks to its strong efficacy and safety profile. But its unquestioned run at the top now appears under threat.
Doubts about the ability of Regeneron to succeed in phase 3 trials of its high-dose version of Eylea and growing confidence in Roche’s newly approved challenger Vabysmo have led analysts at SVB Leerink to slash their future sales estimates for the macular degeneration blockbuster.
In 2027, SVB now sees sales of Eylea reaching $3.4 billion in the U.S., down from a previous estimate of $4.6 billion, the team said in a note to clients.
It’s a big comedown from last year when Regeneron posted Eylea sales of $5.8 billion in the U.S., while overseas marketing partner Bayer registered Eylea revenue of 2.9 billion euros ($3.1 billion).
In addition, SVB has dropped Regeneron from an “outperform” ranking to “market perform” and lowered its price target from $738 per share to $630.
One problem for Eylea is Vabysmo, which was approved by the FDA in January and requires fewer doses. The SVB team said it sees the drug as a "growing competitive threat."
For its part, Regeneron is investigating a longer-lasting formulation of Eylea in two study arms—one dosing patients every three months and the other every four months. The study is comparing the results against Eylea's current two-month regimen.
SVB believes the three-month version can match the two-month performance but that the drug will struggle to keep pace in the four-month trial arm.
“Historical trials of anti-VEGF agents have shown that a meaningful percentage (40%-50%) of patients do not respond well to dosing intervals longer than eight weeks at one year no matter what the dose,” SVB points out. “If high-dose Eylea only shows non-inferiority for 12-week dosing, it would be at a competitive disadvantage to Vabysmo.”
The team said it's basing some of its assessment on a discussion with two key opinion leaders who have extensive clinical trial experience with anti-VEGF agents.
The analysis comes less than two weeks after Roche revealed data that showed Vabysmo was equally effective as Eylea and doesn’t have to be dosed as often. While patients on Eylea are dosed every two months, 63% of those on Vabysmo—after an indoctrination period—could go four months between injections, and 80% could go at least three months between shots.
The opinion leaders told SVB that the way the Vabysmo trials were structured—by optimizing patient selection—helped ensure their success. By contrast, in Regeneron’s trial, which is set to read out in the fall, patients are randomized into the 12-week and 16-week arms.
Additionally, another disadvantage for Regeneron in the structure of its study: It is a fixed-dosage trial as opposed to Roche’s study, which allowed doctors to adjust the dosage depending on patient results.
One of the opinion leaders told SVB that Regeneron was “swinging for the fences” with a fixed-dosing trial design. The other said it would be a “home run” if Regeneron were able to deliver strong results in the 16-week arm.