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Regeneron Beats Genentech In Rare Face Off Over Diabetes-Related Vision Loss

This article is more than 9 years old.

Drug companies usually avoid head-to-head clinical trials against tough competitors. Most prefer to spend their money showing they can beat a placebo, or old treatment. But head-to-head studies of powerful new drugs sometimes get done.

Today, two companies with billions at stake—Genentech and Regeneron Pharmaceuticals —are slugging it out over a trial that sought to determine who has the best eye drug for many people with diabetes. Neither company paid for the study or controlled its design, but Regeneron was able to walk away declaring victory.

The latest round in the Genentech vs. Regeneron battle is being described today in a study of 660 patients with diabetic macular edema—a leading cause of vision loss. The study found Regeneron’s afilbercept (Eylea) offered greater visual improvement than both Genentech’s ranibizumab (Lucentis) and bevacizumab (Avastin) in patients who entered the study with poor eyesight of 20/50 or worse. The three drugs, which bind with the same target to stop abnormal blood vessels from forming in the eye, provided similar vision improvements in people with more moderate vision loss. No major differences in safety were observed.

Results of the study, sponsored by the National Institutes of Health and conducted by an independent physician group,were published online today in the New England Journal of Medicine. Regeneron offered an early glimpse of the results to its stockholders in October, which sent its shares soaring.

The new study will likely help Regeneron gain market share in a field long dominated by Genentech. The biotech pioneer transformed ophthalmology a decade ago when it first won FDA approval for Lucentis—the first drug of its kind for the “wet” form of age-related macular degeneration that could improve eyesight. Groundbreaking as it was for a leading cause of blindness in the elderly, Lucentis came with a high price. Many physicians sought a way around the problem by using another Genentech drug (Avastin) that was developed for cancer, but could be compounded at pharmacies into much smaller and cheaper doses needed for eye diseases.

Regeneron’s drug arrived on the U.S. market in late 2011 with strong claims of effectiveness. Both companies have been seeking to expand their markets into various eye diseases related to formation of abnormal blood vessels in the retina. Lucentis won FDA clearance for diabetic macular edema in the summer of 2012, and Regeneron got the regulatory green light for those patients last summer. An estimated 750,000 people in the U.S. are affected by diabetic macular edema, and incidence is rising along with the rising tide of diabetes.

“This is a very important study,” said Jacque Duncan, a professor of clinical ophthalmology at the University of California, San Francisco, who wasn’t involved in the study. “It’s rare we have a well-designed, multi-center, randomized clinical trial that compares FDA approved treatments head-to-head.” The results in favor of Regeneron were “pretty convincing,” and likely to sway prescribing habits of many doctors, Duncan said. “Physicians who wish to practice evidence-based medicine will be intrigued,” she said.

Even with evidence mounting, Regeneron still has to make its case against Avastin, which has repeatedly been shown to be effective at a fraction of the cost. Many insurers prefer ophthalmologists to try it first for that reason. “Some people, I don’t won’t to say they’re fanatical, but they believe in the power of Avastin and the cost-effectiveness of it,” said Ted Leng, a clinical assistant professor of ophthalmology at the Byers Eye Institute at Stanford University School of Medicine. Leng wasn’t involved in the study.

Data from the study were collected from 89 clinical sites, and analyzed by the Diabetic Retinopathy Clinical Research Network. Patients who entered the study were randomly assigned to get one of the three study drugs, with a goal of measuring visual acuity after one year. People in the study were 61 years old on average, and had had a form of diabetes for an average of 17 years. When looking at all the patients, researchers saw that those on Regeneron’s Eylea were able to see an average of 13 more letters on the eye chart after a year, compared with 11 letters for Genentech’s Lucentis and 10 letters for Genentech’s Avastin.

That difference, authors of the New England Journal paper wrote, isn’t clinically meaningful on its own. But when researchers looked at patients who started the study with the worst eyesight—those with the most room to improve—the Regeneron drug flexed its muscles. Patients in that group, with 20/50 vision or worse at the start of the study, were able to read an average of 19 more letters on the eye chart when they took the Regeneron drug. That compared with 14 letters for Lucentis, and 12 letters for Avastin. The difference was both statistically significant—meaning it was unlikely the result of chance—and clinically meaningful, researchers said.

“This comparative effectiveness study will help doctors and patients make informed decisions when choosing treatments for diabetic macular edema,” said Paul Sieving, director of the National Eye Institute, in a statement.

Regeneron obviously has a huge stake in making sure that physicians prescribe the drug, which is the company’s bestseller. George Yancopoulos, the company’s chief scientific officer, declared victory, both in his drug’s advantage in visual acuity, and on an anatomical measurement that showed it was better at stopping blood vessel blockages in the retina. “It’s clear that Eylea outperformed the other anti-VEGF agents,” he said.

Dr. Jason Ehrlich, Genentech’s group medical director for ophthalmology, said the NIH-sponsored study was well-designed. It reinforced findings from earlier company-sponsored studies that showed the benefit of Lucentis, he said. The Genentech drug, as the first mover in the market, naturally has the most long-term body evidence, with more than 9,000 patients studied over 14 years. “We’ve generated a tremendous amount of information about the safety and efficacy of Lucentis across many retinal vascular diseases, and the results need to be interpreted in that context,” Ehrlich said.

Although doctors have plenty of hard clinical data to sort through in the New England Journal paper, that’s not the only factor at work. Drugs for the eye represent a huge and growing business. Regeneron generated $1.7 billion in net U.S. sales in 2014 from Eylea, mainly from patients with macular degeneration, because it’s still so new for diabetic macular edema. Roche, Genentech’s parent, reported revenue of 1.7 billion Swiss francs (roughly $1.8 billion) last year, with much of the growth attributable to diabetic macular edema.

Cost of the drugs has long been a source of controversy. On a per-injection basis in the doses used for the NIH-sponsored study, Eylea cost $1,960, while Lucentis cost about $1,200 and Avastin cost about $70. Avastin is much cheaper because it is purchased in a higher dose form as a cancer drug, and then packaged into smaller doses at a compounding pharmacy. Genentech has long argued that such usage is inappropriate because Avastin wasn’t designed for use in eye diseases, and the compounding process raises safety concerns.

The true cost to the system, Regeneron’s Yancopoulos said, is hard to measure. Although the Regeneron drug was most expensive in this study, he said that patients required one less injection on average, and a lower rate of rescue laser treatments for patients who weren’t responding. While both companies seek to mitigate the financial blow to patients, Genentech has offered rebates to physicians who prescribe Lucentis to give them more of a financial incentive to prescribe it. The rebate practice, which was questioned in an accompanying editorial in the New England Journal, isn’t used at Regeneron, Yancopoulos said. “We don’t use any rebate-based incentives to buy us more physician use. We’d rather have the data speak for itself,” Yancopoulos said.