The company also provided an update on tarcocimab development program for the treatment of neovascular age-related macular degeneration and diabetic macular edema.
Kodiak Sciences Inc has announced topline results from 3 phase 3 studies of tarcocimab tedromer.
The first of the 3 studies, DAYLIGHT, was a randomized, double-masked, active comparator-controlled study evaluating the efficacy and safety of a high-intensity dosing regimen of tarcocimab tedromer in 557 treatment-naïve subjects with wet age-related macular degeneration (AMD).
According to a press release from the company,1 the “DAYLIGHT study met the primary endpoint of non-inferior visual acuity gains for tarcocimab dosed monthly compared to aflibercept dosed every 8 weeks following 3 monthly loading doses.”
The 2 other studies, GLEAM and GLIMMER, are identically designed, randomized, double-masked, active comparator-controlled studies evaluating the efficacy, durability and safety of tarcocimab tedromer in 460 and 457 treatment-naïve subjects with diabetic macular edema (DME).
According to the company, the GLEAM and GLIMMER studies did not meet their primary efficacy endpoints of showing non-inferior visual acuity gains for tarcocimab dosed every 8 to 24 weeks after 3 monthly loading doses compared to aflibercept given every 8 weeks after 5 monthly loading doses.
The company noted that an increase in cataracts was observed over time in the tarcocimab arms of both GLEAM and GLIMMER, and Kodiak's initial evaluation suggests that this contributed “meaningfully to the failure of each study.”1
The company states based on these data, they have made the decision to discontinue further production of tarcocimab.
Victor Perlroth, MD, Kodiak's chief executive officer explained the decision in the press release.
"A successful efficacy, durability and safety outcome in both GLEAM and GLIMMER was the basis of our regulatory and clinical development strategy for tarcocimab," said Perlroth. "After our unsuccessful Phase 2b study in wet AMD last year, we made a number of changes to the GLEAM and GLIMMER study design to increase their probability of success, and we saw the positive impact of those changes in the GLEAM and GLIMMER data.”
Perlroth continued in his explanation of the results from the trials in the release.1
"We have gained three main insights from the initial data analysis. First, through the matched three loading doses, vision and anatomic improvements were strong and comparable between tarcocimab and aflibercept. Second, in a subset of patients to be determined, additional loading doses with tarcocimab might have helped better achieve early disease control to set an even higher visual acuity base entering into the dose interval adjustment phase, but the overall effect of this was not a primary driver of study failure. Third, and most critically, an unforeseen imbalance in cataract adverse events emerged in the last third of the study (19% of patients on tarcocimab versus 9% of patients on aflibercept by the primary endpoint), and we believe this likely was the primary driver for tarcocimab failing to achieve BCVA non-inferiority to aflibercept in these studies,” said Perlroth.
Finally, Perlroth explained what led to the discontinuation of development.1
“A sub-analysis of the pseudophakic patients (who enter the study having already had cataract surgery) and who represented 25% of the total study population supports this view as does initial analysis of the OCT anatomic data from the two studies. The development of cataracts did not appear to correlate with the timing or number of tarcocimab doses patients had received. Importantly, in the DAYLIGHT study which explored a maximal, monthly regimen of tarcocimab 5mg in wet AMD patients, a median of 12 tarcocimab doses were given over one year and patients experienced fewer events of cataract on tarcocimab than on aflibercept (3% versus 5%). Thus, what drove the increased incidence of cataracts with tarcocimab in DME remains unclear at this time. Given these findings and results, we are discontinuing development of the tarcocimab program," concluded Perlroth.
Detailed results of the GLEAM and GLIMMER studies are scheduled to be presented by study investigator Charles C. Wykoff, MD, PhD, as a late-breaking presentation at the 41st Annual Scientific Meeting of the American Society of Retina Specialists.