- A combination of Regeneron Pharmaceuticals Inc.'s Eylea and one of the company's investigational medicines won't be heading into Phase 3 testing now that early readouts from two mid-stage clinical trials have shown the pairing wasn't significantly more effective than the blockbuster drug alone.
- The RUBY and ONYX studies tested Eylea plus nesvacumab in different diseases — the former for diabetic macular edema (DME), the latter for wet age-related macular degeneration (AMD) — yet investigators for both found there wasn't "sufficient differentiation" between the combo and Eylea monotherapy in terms of added benefit to patients.
- Nesvacumab is an antibody that targets a protein called angiopoietin2 (Ang2), which researchers have found contributes to tumor development through regulating angiogenesis. Notably, angiogenesis also plays a role in many eye diseases.
First approved in late 2011, Eylea (aflibercept) accounts for the vast majority of Regeneron's income. The drug's U.S. net product sales totaled $953 million in the third quarter alone, and executives anticipate it will hit 10% annual growth in 2017. That growth would equate to roughly $3.65 billion worth of revenue, adding yet another blockbuster year under Eylea's belt.
Developing the next act to follow Eylea has been a difficult endeavor for Regeneron, however. In September 2016, the Tarrytown, New York-based biotech announced that adding its investigational drug rinucumab, an anti-platelet derived growth factor receptor beta antibody, to Eylea didn't end up improving visual acuity for patients with wet AMD in a Phase 2 study.
Regeneron ended up discontinuing the rinucumab study; and while the company noted the challenge of finding a treatment more effective than Eylea, it turned its focus to the nesvacumab combo. But the RUBY and ONYX results indicate that the search may be far from over.
"We knew from the start that it would be difficult to improve on the already high bar set by Eylea, which is the market-leading branded therapy in its approved indications, providing significant improvements in vision and strong long-term outcomes in patients with wet AMD and DME," George Yancopoulos, Regeneron's chief scientific officer, said in a Monday statement.
Meanwhile, rival drugmaker Novartis AG is speeding toward market with its own investigational wet AMD drug. The Swiss pharma revealed in July positive results from the Phase 3 HAWK and HARRIER studies that demonstrated its medicine, named RTH258, was non-inferior to Eylea.
Novartis also touted the 6 mg dose of RTH258 was effective for longer than Eylea, which the Food and Drug Administration approved for injection every eight weeks. To that end, locking down a less frequent dosing regimen could give RTH258 a foothold to compete.
Not to be outdone, Regeneron plans to file a 12-week dosing regimen of Eylea by year's end. The company is also investigating the blockbuster drug in diabetic retinopathy, and expects data from a late-stage trial for that indication to come in the first half of 2018.
Regeneon stock opened at $379 per share Monday, and was down 3% in morning trading.