Wall Street fell short of rejoicing when Regeneron Pharmaceuticals Inc. popped the lid off Phase III data with sarilumab that met all endpoints in rheumatoid arthritis (RA), and the firm’s chief scientific officer, George Yancopoulos, said he knows why.
“If we were a different sort of company, this would have been a company-making or -breaking announcement, but a lot of people are viewing it as just another delivery from Regeneron,” he said.
“People consider us a mature company that has a lot of things going on,” Yancopoulos said. “We’re no longer a company where a Phase III program does a huge thing to the stock. What it speaks to is the depth and productivity of our organization.”
Shares (NASDAQ:REGN) closed Friday at $293.68, up $17.27.
The first fully human anti-IL-6R monoclonal antibody in RA, sarilumab was tested in patients who didn’t adequately respond to methotrexate (MTX). Combined with MTX, the drug, given every other week, improved disease signs and symptoms as well as physical function, and inhibited progression of joint damage.
Yancopoulos, who is also Tarrytown, N.Y.-based Regeneron’s founding scientist and president, called sarilumab – partnered with Paris-based Sanofi SA – “a competitive agent in an emerging therapeutic class that’s going to be critical in this disease and perhaps other disease categories.”
Signs and symptoms of improvements were measured by 20 percent gain in the American College of Rheumatology score (ACR20) at 24 weeks. They totaled 66 percent with 200 mg sarilumab, 58 percent with 150 mg sarilumab and 33 percent with placebo, all in combination with MTX.
Whether the subcutaneous drug inhibited more structural damage was measured by a change in the modified Van der Heijde total Sharp score at week 52. Those improvements amounted to 0.25 with 200 mg sarilumab, 0.90 with 150 mg sarilumab and 2.78 with placebo – all in combination, again, with MTX.
Bettered physical function, the third endpoint, was determined by a change from baseline in the Health Assessment Question-Disability score at 16 weeks
A 90 percent decrease in radiographic advance was seen in the 200-mg dose group vs. the placebo group, and safety findings turned up consistent with results from previous studies of sarilumab, but did include more infections and adverse events leading to withdrawal in the patient groups given sarilumab.
More Eylea Potential
All in all, analysts found, sarilumab looks as efficacious in RA as Actemra (tocilizumab), the first interleukin-6 receptor monoclonal antibody approved in the U.S., from Genentech, a unit of Basel, Switzerland-based Roche AG.
“Actemra has set a bar, and it’s an important bar,” Yancopoulos said. “The opportunity to have a second-in-class drug that is competitive and may even have some advantages could lead to a huge opportunity. That was certainly the story with the [anti-tumor necrosis factor drugs] in the same space,” he noted.
“What we were trying to do was come up with an every-other-week regimen, where we had two doses to provide flexibility to doctors and to patients, so that the higher dose would be in some ways competitive with their weekly dosing paradigm and the low dose might be competitive with their once-every-two-week paradigm, which they just launched,” he said. “Clearly the benefit with the higher dose, relative to placebo, is as good as anything that’s been achieved, and you have a slightly lower dose for patients who might have tolerability issues and so forth.”
Disease-modifying drugs that prevent joint destruction make up a “hot-button issue in the field,” and finding the right therapies has been “creating huge hurdles for the JAK kinase inhibitor programs,” such as New York-based Pfizer Inc.’s, Yancopoulos said. “It looks like, once again, we can say the data produced with sarilumab are as good as any that’s been produced in the field.”
Full results from the Phase III trial, called Mobility, will be presented at an upcoming medical conference, and three more are enrolling in RA, called Target, Ascertain and Compare. Though both doses of sarilumab showed clinically relevant and statistically significant improvements compared to placebo in all three co-primary endpoints (p < 0.0001), it was the 200-mg dose that analysts found a likely contender against Actemra.
Regeneron also disclosed approval in Japan of Eylea (aflibercept) for central retinal vein occlusion (CRVO). Sales of the blockbuster drug grew 23 percent in the third quarter over the same period last year. In the U.S., European Union (EU) and Japan, it was already approved for wet age-related macular degeneration (AMD); Eylea was approved earlier for CRVO, too, in the U.S., and the EU and Japan already had the AMD label.
The company submitted a supplemental biologics license application (sBLA) for Eylea in diabetic macular edema (DME) a year ahead of schedule and recently disclosed positive Phase III results in branched retinal vein occlusion, for which an sBLA is due in the months ahead.
DME, Yancopoulos told BioWorld Today, is “a huge opportunity in the U.S. and worldwide. It’s going to be much larger than CRVO, which is a phenomenally important setting because it [strikes] patients who acutely lose vision, and we can show that the drug benefits those patients, but it’s a relatively small population.”