'Unexpected' cataracts in phase 3 trials end Kodiak's hopes for eye drug, halving stock price

Kodiak Sciences has blamed an “unexpected increase in cataracts” as a reason for the failure of a pair of phase 3 trials that have led the biotech to drop its antibody biopolymer conjugate and halved its share price.

The anti-VEGF drug, called tarcocimab tedromer, was being assessed in two identical late-stage trials dubbed GLEAM and GLIMMER in 460 and 457 patients, respectively, with diabetic macular edema (DME). Neither study met its primary endpoint of showing non-inferior visual acuity gains after 64 weeks when compared to Regeneron’s approved therapy Eylea.

Despite tarcocimab tedromer having demonstrated efficacy in a separate trial of 557 patients with neovascular age-related macular degeneration (AMD)—the results of which Kodiak also unveiled today—the biotech said it had “made a business decision to discontinue further development of tarcocimab.”

In a pre-market release Monday, Kodiak CEO Victor Perlroth, M.D., explained that the company’s plans for the antibody had been based on achieving success with both the GLEAM and GLIMMER trials. In the wake of a failed phase 2b study in wet AMD last year, the Palo Alto, California-based biotech had already amended the design of both studies to increase their chances of success.

“After getting these results, the immediate question is why did the GLEAM and GLIMMER studies fail?" Perlroth said in the release.

Searching for a potential culprit, the company pointed to “an unforeseen imbalance in cataract adverse events” that appeared in the final third of the study. A total of 19% of patients on tarcocimab experienced these cataracts in the two studies, compared to 9% of patients on Eylea.

“We believe this likely was the primary driver for tarcocimab failing to achieve BCVA non-inferiority to aflibercept in these studies,” Perlroth said.

But as the development of cataracts didn’t appear linked to the timing or number of tarcocimab doses a patient received, and a similar increase in cataracts wasn’t observed in the successful AMD trial, the biotech was still left scratching its head.

“What drove the increased incidence of cataracts with tarcocimab in DME remains unclear at this time,” Perlroth said. “Given these findings and results, we are discontinuing development of the tarcocimab program.”

Kodiak ended June with around $379 million in cash and equivalents, which the CEO said gave the company “significant optionality following the wind-down of the tarcocimab program.”

“We will be assessing our capabilities and the many learnings gained by Kodiak during the development of tarcocimab as we reset our near-term plan.”

It didn’t appear to be enough to reassure jittery investors, who sent Kodiak’s stock plummeting 56% to $3.18 per share in pre-market trading from a Friday closing price of $7.29.

The case of the mysterious cataracts could even upend Kodiak’s plans for its other clinical-stage candidate, called KSI-501, a bispecific inhibitor of both IL-17 and VEGF in a phase 1 study for DME. Perlroth suggested that the biotech might continue to investigate KSI-501 as a retina program while “decreasing our reliance” on its antibody biopolymer conjugate (ABC) platform that was used to create both KSI-501 and tarcocimab.