Novartis has been losing ground in the age-related macular degeneration (AMD) market, but a pair of positive phase 3 trials for new drug brolucizumab (aka RTH258) suggests a comeback could be on the cards.
AMD affects up to 25 million people worldwide and is the leading cause of early blindness in the industrialized world, and for some years Novartis' VEGF inhibitor Lucentis (ranibizumab) was the leading treatment for the wet or 'neovascular' form of the disease.
Latterly however the drugmaker, along with partner Roche, has been in a toe-to-toe battle with Bayer and Regeneron, whose rival VEGF/PIGF inhibitor Eylea (aflibercept) has been in the ascendency despite Lucentis' first-to-market advantage.
Eylea's rapid growth has been put down to a lower per-dose price as well as a less-frequent dosing schedule (typically every eight weeks versus once a month for Lucentis).
Now, Novartis says it now has data from two phase 3 trials—HARRIER and HAWK—showing that long-acting VEGF brolucizumab matches Eylea when dosed just four times a year. And analysts at Jefferies think this dosing schedule is "a significant differentiator and competitive advantage" for the Swiss group's new candidate, which is now heading for regulatory filings next year.
The new drug (at 6-mg and 3-mg doses) matched Eylea (2-mg) in the average change in best-corrected visual acuity (BCVA) over 48 weeks, and the two drugs had comparable side-effect profiles. More than half of the patients in HAWK and HARRIER (57% and 52% respectively) received brolucizumab every 12 weeks, with the remainder.
"Given these treatments are dosed via intravitreal injection directly into the eye, the ability to show non-inferiority on efficacy, but with injections given every 12 weeks instead of the more frequent dosing for the competitors … will be a key determinant to RTH258’s likely future success," said Jefferies' Jeffrey Holford in a research note, who predicts a US launch in 2019 and peak sales of $2 billion if it also claims approval in diabetic macular edema.
"We will now have to await presentation of these studies at an upcoming conference to see the full details, but the fact that RTH258 managed to meet the primary and key secondary endpoints at both the 6-mg and 3-mg dose should help underpin the perception of its potency," he added.
If all goes to Novartis' plan, brolucizumab could transform its AMD franchise, particularly after a big disappointment last year when its pegpleranib—an anti-PDGF aptamer originally developed by OphthoTech—failed phase 3 trials. It's also facing the threat of biosimilar competition to Lucentis.
Roche, which sells Lucentis in the U.S., reported sales down 10% to $1.44 billion last year, while Novartis' ex-U.S. sales dropped 11% to just over $2 billion. Eylea meanwhile grew 24% to $3.3 billion in the U.S.—where it is sold by Regeneron—with Bayer reporting sales up a third to €1.63 billion ($1.1 billion) in ex-U.S. markets.