Another attempt to use a combination of drugs to improve upon the current treatments for age-related macular degeneration, a leading cause of vision loss in the elderly, has failed. The news is a setback for Tarrytown, NY-based Regeneron Pharmaceuticals (NASDAQ: REGN), which is trying to fend off the competition for its most successful drug, a therapy for AMD.
Regeneron said in a statement Monday morning that experimental nesvacumab and FDA-approved aflibercept (Eylea), a closely watched eye drug combination being tested in multiple Phase 2 trials, “did not provide sufficient differentiation to warrant Phase 3 development.”
Regeneron didn’t disclose specifics of the two trials, Ruby and Onyx, which had been testing the combination against aflibercept alone in patients with either AMD or diabetic macular edema. It will share the data at an unspecified future medical meeting.
AMD affects more that 2 million Americans, a number expected to grow to nearly 5.5 million by 2050 as the population ages, according to the National Eye Institute. About 10 to 15 percent of those patients have the more severe or “wet” form, when abnormal blood vessels form in the eye and leak fluid, ultimately causing potentially significant vision loss.
The market for AMD treatments has exploded in the past several years. Until recently, the standard of care was laser therapies that didn’t actually improve patients’ vision. That method has been replaced by injectable pharmaceuticals. Two drugs, aflibercept and ranibizumab (from Genentech/Novartis), are specifically approved for the condition. The most widely used drug for wet AMD, bevacizumab (Avastin), is prescribed off label. These drugs are given frequently, as often as every month. Aflibercept and ranibizumab generate more than $7 billion in annual worldwide sales combined.
These wet AMD drugs—which block a protein called VEGF and stop abnormal blood vessels from forming—can restore some vision, prevent further damage to the eyes, and stop people from going blind. But they aren’t cures, and there is room for improvement. Over the past few years, multiple drug combinations have been attempted to try to improve upon VEGF blockers, either by boosting their effectiveness or requiring fewer injections, only to fail in clinical testing. Ophthotech tried to show that adding another drug, pegpleranib, that worked by a different, potentially complementary mechanism (it blocks a different protein, PDGF), might restore even more vision for patients. That drug failed multiple Phase 3 trials. Regeneron tried that combination as well with a drug called rinucumab, but a Phase 2 study came up short in September 2016. At the time, chief scientific officer George Yancopoulos said in a statement that the preclinical data were “more supportive” for combining aflibercept with a drug that blocks a different protein, angiopoietin 2 (ANG2), instead. ANG2 is the target of nesvacumab.
In the statement Monday morning, Yancopoulos said the company “knew from the start that it would be difficult to improve upon the already high bar set by [aflibercept].” Aflibercept is already approved for AMD, macular edema following retinal vein occlusion, and diabetic retinopathy in patients with DME. Regeneron is trying to build on that with a Phase 3 study, Panorama, in patients who have diabetic retinopathy but not DME. Results are expected in 2018.
Yet the combination treatment was meant to address more immediate competitive threats to aflibercept. Despite the recent approvals of Regeneron antibody drugs for high cholesterol, rheumatoid arthritis and eczema, aflibercept remains by far the company’s biggest revenue driver, accounting for $3.3 billion of Regeneron’s roughly $4.9 billion in sales in 2016 and $953 million of its $1.5 billion in sales during the most recent quarter. Just last month, Novartis presented data from two Phase 3 trials of an emerging, rival anti-VEGF blocker, brolucizumab, that showed it may be at least comparable—and by some measures superior—to aflibercept, and may require less frequent injections.
Regeneron shares dipped close to 3 percent in pre-market trading on Monday.