Kodiak resurrects failed eye drug after phase 3 data rejuvenate approval prospects

Kodiak Sciences gave up on tarcocimab tedromer earlier this year after a pair of phase 3 trials ended in failure. But a fresh batch of late-stage data has now given the anti-VEGF drug another shot at approval.

Kodiak announced this morning that it will “reboot” the program after a 5-mg dose of tarcocimab tedromer met the primary endpoint in one-year data from the GLOW trial in non-proliferative diabetic retinopathy (NPDR).

A total of 41.1% of evaluable patients who received tarcocimab demonstrated at least a two-step improvement on the Diabetic Retinopathy Severity Scale versus 1.4% of evaluable patients in the sham group, meeting the study’s primary endpoint.

This marks a stunning turnaround for the drug’s fortunes after the biotech blamed an “unexpected increase in cataracts” for sinking tarcocimab’s chances of succeeding in a pair of identical trials evaluating the anti-VEGF drug against Regeneron and Bayer’s blockbuster Eylea in diabetic macular edema (DME). Those failures were especially galling for the Palo Alto, California-based biotech as it had already amended the design of both studies to increase their chances of success after a failed phase 2b study in wet age-related macular degeneration (AMD) last year.

The rates of serious ocular adverse events and intraocular inflammation were similar between the tarcocimab and the sham cohorts, the company noted.

Despite its past clinical woes, Kodiak executives said that the latest GLOW results, coupled with the drug’s success last year in matching Eylea in a phase 3 trial of macular edema due to retinal vein occlusion (RVO), now support rebooting the program.

The pair of phase 3 failures in July also cast into doubt the feasibility of Kodiak’s other clinical-stage candidate called KSI-501, a bispecific inhibitor of both IL-17 and VEGF in a phase 1 study for DME. But, now, the biotech has said the positive tarcocimab data mean the company will continue to pursue KSI-501 as both an enhanced bispecific and a bispecific-free protein.

The company ended June with $378.7 million in cash and equivalents, and Kodiak said this morning that it has sufficient funds to develop tarcocimab alongside the two different versions of KSI-501.

“This is the first time that six-month dosing in all patients succeeded in treating diabetic retinopathy, which we believe is a meaningful and clinically relevant achievement,” J. Pablo Velazquez-Martin, M.D., senior vice president of clinical sciences at Kodiak, said in the release.

"We think that the consistency of the data across all endpoints, where tarcocimab significantly improved the diabetic eye disease status and, importantly, significantly prevented sight-threatening complications, is remarkable,” Velazquez-Martin added.

Kodiak CEO Victor Perlroth, M.D., said recent discussions with the FDA have included the GLOW data. The company is now hoping to submit a single approval application to the agency for tarcocimab that spans wet AMD, RVO and NPDR—but will first need to return to the clinic one more time.

“We believe we have a clear regulatory pathway requiring one additional positive study to support a single BLA submission for all three indications,” Perlroth said.

Investors appear to be reserving their judgment, with Kodiak’s stock still sitting at $2.12 in premarket trading Monday, a far cry from the $7.29 share price it commanded before the phase 3 fails in July.