Kodiak ends attempt at an Eylea rival as its biologic fails two of three PhIII trials

Kodiak Sciences’ attempt at making an Eylea rival for patients with various eye conditions has come to an end.

The California biotech is scrapping its late-stage biologic after it failed two of three Phase III trials. Investors halved Kodiak’s shares $KOD before Monday’s opening bell.

The anti-VEGF candidate, tarcocimab tedromer, succeeded at showing non-inferiority to Regeneron’s Eylea in one study of 557 patients with wet age-related macular edema, or wet AMD, a big contributor to blindness. But tarcocimab failed to show non-inferiority to the Regeneron blockbuster in two late-stage studies of patients with diabetic macular edema, or DME.

It’s the final straw for Kodiak’s treatment candidate. In early 2022, the drug, called KSI-301, failed a key clinical trial against Eylea in wet AMD but had a turnaround story in August of that year when tarcocimab succeeded in a late-stage trial for retinal vein occlusion.

With Monday’s setbacks, the Palo Alto biotech decided to cull further development of tarcocimab. In the two new failed studies, at about 460 patients each, Kodiak pointed to an “unexpected increase in cataracts” in the tarcocimab arms. An early analysis of the data “suggests that this contributed meaningfully to the failure of each study.”

Victor Perlroth

Kodiak CEO Victor Perlroth said the company had altered the two failed studies, dubbed GLEAM and GLIMMER, after the 2022 setback to “increase their probability of success.”

“After getting these results, the immediate question is why did the GLEAM and GLIMMER studies fail?” Perlroth asked in the company’s Monday morning press release.

He answered himself with three observations: the three loading doses of both tarcocimab and Eylea showed vision and anatomic improvements that were “comparable.” In a subset of patients, more loading doses of Kodiak’s candidate might have led to better visual acuity going into the rest of the study, “but the overall effect of this was not a primary driver of study failure,” Perlroth said. Lastly, “and most critically,” the cataract adverse event imbalance was “unforeseen” — 19% of those on Kodiak’s treatment versus 9% on Eylea.

The CEO said they don’t know why there were more incidences of cataracts.

In GLEAM, the average visual acuity gains were 6.4 eye chart letters for those on Kodiak’s anti-VEGF and 10.3 letters for those on Eylea. In GLIMMER, the results were 7.4 letters and 12.2 letters, respectively, per Kodiak medical chief Jason Ehrlich.

“While we have not come to a final conclusion, we remain committed to our vision and mission of developing transformative therapies for high prevalence diseases,” the CEO said. “In this regard, we believe our KSI-501 program has a differentiated mechanism of action targeting both IL-6 mediated immune-inflammation as well as VEGF mediated angiogenesis and vascular permeability.”

KSI-501 is in a Phase I multiple dose escalation study. The company might make adjustments to the program based on the late-onset cataracts observed in the other trials, Kodiak said.

The company had about $379 million in cash and cash equivalents at the end of June, Perlroth said. The pipeline also includes a so-called triplet platform, protein therapeutic candidates and small molecules.

Trial investigator Charles Wykoff is set to deliver more results in a late-breaking presentation on July 30 at the American Society of Retina Specialists’ annual meeting.

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