Debate over market prospects was renewed by the publication of full outcomes from the Protocol T study comparing Regeneron Pharmaceuticals Inc.'s Eylea (aflibercept) with Roche AG unit Genentech's Lucentis (ranibizumab) and Avastin (bevacizumab) against moderate to severe vision loss in patients with diabetic macular edema (DME).

In the 660-patient study sponsored by the NIH and published in the New England Journal of Medicine (NEJM), Eylea beat the other drugs specifically in patients whose eyesight is 20/50 or worse when visual acuity was measured at one year.

An editorial about the data in the NEJM favored first-line use of Eylea from among the anti-vascular endothelial growth factor (VEGF) therapies in patients with poorer vision, but said about 75 percent of DME patients in the general population have vision of 20/40 or better, which means about 25 percent would be eligible for the drug, partnered with Leverkusen, Germany-based Bayer AG.

But Protocol T's enrollment shows 49 percent of patients turned up with 20/50 vision or worse, so Eylea may grab more of the market share than the editorial suggested. Regeneron's guidance calls for U.S. sales growth of 25 percent to 30 percent, or $2.17 billion to $2.26 billion, and Piper Jaffray forecasts $2.22 billion. In 2014, sales rose 23 percent to $1.74 billion, compared to $1.7 billion for Basel, Switzerland-based Roche with Lucentis.

Company officials were traveling and could not be reached, but during Tarrytown, N.Y.-based Regeneron's conference call on fourth quarter earnings earlier this month, CEO Leonard Schleifer said that "in terms of Protocol T and our guidance, everything we know went into the mix, and what came out was our best guess," adding that the company would wait "until we see how it gets received and how quickly it might or might not influence behavior. We hope it will. Things could change."

Price is an issue. Eylea goes for about $1,950, Lucentis for about $1,200 and Avastin – which performed favorably to the other two in people whose eyesight was less bad – is priced at just $50, indicating physicians may choose it for the less severe cases.

As the official sponsor, the Diabetic Retinopathy Clinical Research Network noted in a description of the trial that "although Eylea has a similar cost per unit dose to Lucentis, it has the potential to decrease treatment burden and associated cost. If results from a comparative trial demonstrate improved efficacy or suggest similar efficacy of Avastin or Eylea over Lucentis, this information might give clinicians scientific rationale to substitute either one of these drugs for Lucentis in the treatment of DME, and might thereby have substantial implications for public policy in terms of future estimates of health care dollars and possibly number of treatments necessary for anti-VEGF treatment of diabetic macular disease."

What's more, "because of its availability and lower cost, Avastin is already currently in widespread clinical use for treatment of DME despite the lack of FDA approval for this indication. Thus, a clinical trial that suggested whether Avastin could be used as a safe and efficacious alternative to Lucentis could substantially impact nationwide practice patterns for treatment of DME by either validating the current use of Avastin or by demonstrating improved outcomes with Lucentis or Eylea treatment for DME."

Deutsche Bank analyst Robyn Karnauskas said her discussions with specialists found that "they previously believed that Lucentis and Eylea are somewhat equal in terms of efficacy profile," but new data showing superiority – such as those from the Protocol T study – would cause them to choose Eylea.

"They also hinted at the possibility of these data increasing Eylea uptake in [age-related macular degeneration, AMD] as well," she wrote in a research report.

Biren Amin, analyst with Jefferies, called the Protocol T outcome a "clear win" for Regeneron.

He cited the U.S. Preferences and Trends Survey published in 2014 that suggests retina specialists will drive their use of anti-VEGF agents based on change in visual acuity at one year (38 percent), proportion of eyes with visual acuity gains of two or three lines on a chart (32.5 percent), change in retina thickness as measured by optical coherence tomography (21.4 percent) and number of injections (6.1 percent).

As with Protocol T, it was also the NIH that backed the Comparison of Age-Related Macular Degeneration Treatments Trials, data from which were published in the NEJM in 2011.

The two-year experiment pitted Avastin and Lucentis against each other in their approved indication of AMD and found that they performed about the same. (See BioWorld Today, May 2, 2011.)

Regeneron's stock (NASDAQ:REGN) closed Thursday at $426.60, up $20.80.