Kodiak paused further development of tarcocimab last summer after its GLEAM and GLIMMER studies in diabetic macular edema did not meet their primary endpoint.
Kodiak Sciences has announced its Phase 3 GLOW superiority study evaluating tarcocimab tedromer 5 mg in moderately severe to severe non-proliferative diabetic retinopathy (NPDR) met its one-year primary, and all key secondary endpoints.
Due to this, the company also announced that it will be “rebooting” the tarcocimab tedromer development program, and plans to conduct one additional pivotal study with a commercial formulation of tarcocimab.
The Phase 3 GLOW study investigated an every 24-week tarcocimab dosing regimen for all subjects, versus sham, in patients with moderately-severe and severe NPDR without DME.1
At one year, GLOW met its primary endpoint of the proportion of patients with at least a 2-step improvement on the Diabetic Retinopathy Severity Scale (DRSS) score, a grading system measuring the degree of retinopathy. Tarcocimab achieved a 29-fold increased response rate ratio, with 41.1% of evaluable patients on tarcocimab demonstrating at least 2-step improvement versus 1.4% of evaluable patients in the sham group (p less than 0.0001). Visual acuity and retinal anatomy were improved and stable with tarcocimab on its extended-dosing intervals.1
"This is the first time that 6-month dosing in all patients succeeded in treating diabetic retinopathy which we believe is a meaningful and clinically relevant achievement", J. Pablo Velazquez-Martin, MD, senior vice president of clinical sciences at Kodiak Sciences. "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. The GLOW data reinforce the durability potential of tarcocimab and the antibody biopolymer conjugate platform (ABC Platform) in the management of retinal vascular diseases."
The company believes that the one-year head-to-head BEACON results and primary endpoint and key secondary endpoint GLOW results support the development of 3 clinical prospects: enhanced tarcocimab ABC, enhanced bispecific KSI-501 ABC, and KSI-501 bispecific free protein (not conjugated). The company also stated it believes it has enough capital on hand to further develop all 3 projects in parallel.1
"We have actionable learnings from the tarcocimab clinical program that we used to develop an enhanced commercial formulation of tarcocimab that balances free antibody and conjugated antibody to improve manufacturability and, importantly, to improve usability by reducing injection time from 7-10 seconds to 2-3 seconds. This formulation has already been manufactured at commercial scale and is ready for use in clinical trials. After evaluation of the Phase 3 data across the tarcocimab program and based on conversations with members of the retina community, we believe our commercial tarcocimab formulation could be an important future therapeutic option. As a result, we have decided to run another pivotal study with the intent to file a single BLA for RVO, wet AMD and NPDR. This enhancement to the ABC Platform is also being implemented in our first-in-class anti-IL-6 and anti-VEGF bispecific, KSI-501 ABC," Perlroth said in the press release.
The company also stated it has had dialogue with US regulatory authorities New regulatory strategy could support a single Biologics License Application (BLA) for macular edema following retinal vein occlusion (RVO), wet age-related macular degeneration (wAMD) and NPDR.