Roche is forging ahead with plans to seek approval for an eye disease drug candidate despite missing the primary endpoint in one of its phase 3 trials.
The Swiss drugmaker ran two identical studies, MEERKAT and SANDCAT, to compare two doses of the IL-6 inhibitor vamikibart to a sham control in patients with uveitic macular edema (UME). Interest in targeting IL-6 to treat the eye disease is built on off-label use of tocilizumab, which Roche sells as Actemra. Whereas tocilizumab is given systemically, Roche engineered vamikibart for injection into the eye.
Roche believes it has exited phase 3 with data to support talks with regulatory agencies, but the mixed results raise questions about the chances of approval. More patients gained vision on vamikibart than on the control. However, the result in SANDCAT fell short of statistical significance, causing the trial to miss its primary endpoint.
MEERKAT hit on the same endpoint, which looked at how many patients gained at least 15 letters on the BCVA vision chart at Week 16. In a statement, Roche said “the underlying variability of BCVA as an endpoint, along with variations in patient baseline characteristics and concomitant medications, may have influenced the differences in trial primary outcomes.”
Data on the high dose of vamikibart underpinned SANDCAT’s failure on the primary endpoint. In that trial, 20.7% of patients on the low dose met the primary endpoint success criteria. The result was in line with the 19.9% seen in MEERKAT. Yet the high-dose data diverged, with the 10.9% success rate seen in SANDCAT falling well short of the 36.9% reported in MEERKAT.
Roche reported rapid and clinically meaningful improvements on key secondary endpoints that looked at the average change from baseline in BCVA and a measure of retinal thickness. With these hits to potentially offset missing one primary endpoint, Roche Chief Medical Officer Levi Garraway, M.D., Ph.D., said in a statement that the “totality of data” from the studies represents an important step for UME treatment.
Related
Regulators’ view of that argument will shape the future of vamikibart. Roche has already paused plans to develop the drug in diabetic macular edema, choosing instead to prioritize development of a VEGFxIL6 candidate in that indication. The action leaves Roche looking to UME for a return on its investment in vamikibart.
If approved, vamikibart will enter a market that is largely served by systemic, local and topical steroids. Analysts have relatively low expectations for the molecule’s commercial prospects. A consensus estimate collated by Roche put (PDF) vamikibart at bottom of a list of the phase 3 programs that will contribute the most to growth through 2029.
