Regeneron has halted development of an ophthalmic combination of nesvacumab and Eylea. The decision follows data from two phase 2 trials that tested angiopoietin 2 antibody nesvacumab in combination with Eylea.
Tarrytown, New York-based Regeneron is yet to post data from the trials, saying only that the addition of nesvacumab to its blockbuster Eylea “did not provide sufficient differentiation to warrant phase 3 development.” That decision was based on the results of trials that assessed the efficacy of the combination in 300 patients with diabetic macular edema and a similar number of people with neovascular age-related macular degeneration.
Regeneron and partner Bayer, which paid $50 million to buy into the drug last year, were looking to nesvacumab to shore up their Eylea franchise in the face of intensifying competition. Most notably, Novartis is planning to hit back against Eylea—which challenged its Lucentis—with the long-acting VEGF inhibitor brolucizumab, also known as RTH258. Phase 3 data suggest brolucizumab matches or beats the efficacy of Eylea and has a less burdensome dosing schedule.
The failure of nesvacumab in phase 2 means two of Regeneron’s attempts to improve on Eylea have fallen short. The first setback came 14 months ago, when Regeneron reported the failure of anti-PDGFR-beta antibody rinucumab to improve on Eylea. In between the two setbacks, Novartis and its partner Ophthotech reported on the failure of their anti-PDGF drug to move the needle in phase 3.
Novartis’ fortunes improved with brolucizumab, magnifying the potential impact of the failures of nesvacumab and rinucumab on Regeneron and its critical Eylea franchise. Regeneron is working on a long-acting formulation of Eylea that could compete with brolucizumab. But, even accounting for the manufacturing-related holdup of Novartis’ filing for approval of brolucizumab, Regeneron risks ceding a head start to its competitor.
The nesvacumab and rinucumab clinical trials are potentially-costly blots on Regeneron’s generally-enviable R&D record. Regeneron CSO George Yancopoulos, M.D., Ph.D., framed the rare back-to-back setback as a result of the success of Eylea.
"We knew from the start that it would be difficult to improve on the already high bar set by Eylea,” Yancopoulos said in a statement.