Regeneron's bid for high-dose Eylea scores early win, but the 'all important' data are still to come: analysts

With proof-of-concept data in hand, Regeneron’s top scientist says the company is “cautiously optimistic” that an investigational higher dose of Eylea can benefit wet age-related macular degeneration (wet AMD) patients. If successful, the program could strengthen the company's position against market rivals and biosim challengers.

The company on Tuesday said an 8 mg dose of aflibercept, also known as Eylea, met its primary safety endpoint in an ongoing phase 2 proof-of-concept study comparing the program against the established 2 mg dose. The study, which enrolled 106 people, is part of Regeneron's effort to see whether a higher dose can deliver long-lasting treatment responses with a similar side effect profile.

At the sixteen-week mark, 43.4% of patients on the higher Eylea dose experienced full drying of the retina versus 26.4% in the 2 mg cohort. Meanwhile, safety looked better in the higher-dose arm, too. Seventeen percent of patients on the 8 mg regimen reported side effects, compared with 22.6% in the 2 mg group.

Two major safety events cropped up in the study, one in each cohort: A patient in the Eylea 8 mg group suffered a retinal tear, while another person in the 2 mg cohort experienced a reduction in visual acuity, Regeneron said.

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While the “all-important” data on visual acuity or retinal thickness aren't in yet, things are looking “so far so good” for the higher Eylea dose, Piper Sandler analysts wrote in a note to clients Tuesday. Regeneron concurs.

"We are cautiously optimistic that these early data suggest that a higher dose of aflibercept may potentially benefit patients with wet AMD, and we look forward to Phase 3 data next year, which will be crucial to understand its overall efficacy and safety," George Yancopoulos, M.D., Ph.D., president and chief scientific officer at Regeneron, said in a statement.

The latest results come as investigators test Eylea 8 mg in two large phase 3 studies, one in wet AMD and the other in diabetic macular edema (DME). Both should deliver results in the second half of 2022, the company said in a release.

Still, the Piper Sandler team noted “a healthy level of skepticism” around Regeneron’s program from key opinion leaders. One doctor cited by the analysts flagged Roche’s phase 3 harbor study for Lucentis, which failed to show any benefit from quadrupling the drug's dose.

Regeneron’s latest data are preliminary, but the results “are bound to increase interest in this format for the time being," the analysts wrote.

If 8 mg Eylea’s phase 3 program is successful, the drug could avoid a looming 2027 formulation patent cliff, the Piper Sandler team added. As it stands, biosims from companies like Sandoz, Samsung Bioepis, Celltrion and Amgen are angling to take on the blockbuster.

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Meanwhile, one of Eylea’s chief rivals, Novartis’ Beovu, has been thrown off course since its launch. Novartis in late May scrapped three trials for the VEGF inhibitor early after an interim analysis from its phase 3 Merlin study flagged increased rates of eye inflammation in patients on Beovu, compared with those who received Eylea.

Beovu’s safety saga kicked off shortly after its launch in 2019, when the American Society of Retina Specialists raised the risk of a potential vision-damaging safety complication, which Novartis later confirmed through its own internal investigation.

Eylea reeled in $1.42 billion in second-quarter sales and $1.35 billion in the first three months of the year. The drug ginned up $8.36 billion in 2020, climbing to the no. 6 spot on Fierce Pharma’s annual ranking of the industry’s top-selling meds.