Kodiak Sciences Inc.announced that its phase 3 GLOW superiority study evaluating tarcocimab tedromer 5 mg in moderately severe to severe NPDR met its one-year primary endpoint.
"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", said Dr. J. Pablo Velazquez-Martin, 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," continued, Dr. Velazquez-Martin. "The GLOW data reinforce the durability potential of tarcocimab and the antibody biopolymer conjugate platform (ABC Platform) in the management of retinal vascular diseases."
"We think that durability remains the most clinically relevant unmet patient need," said Dr. Victor Perlroth, CEO of Kodiak. "We now have three successful phase 3 pivotal studies with tarcocimab tedromer across three different retinal vascular and exudative diseases: wet AMD, RVO and NPDR. In recent discussions with the FDA, which included the GLOW data, we believe we have a clear regulatory pathway requiring one additional positive study to support a single BLA submission for all three indications," continued Dr. Perlroth.
"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," Dr. Perlroth concluded.
Kodiak paused further development of tarcocimab last summer after its GLEAM and GLIMMER studies in diabetic macular edema did not meet their primary endpoint, in order to evaluate learnings from its pivotal BEACON study in patients with macular edema due to retinal vein occlusion and from its GLOW study.
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 three attractive clinical prospects: enhanced tarcocimab ABC, enhanced bispecific KSI-501 ABC, and our KSI-501 bispecific free protein (not conjugated) and that Kodiak has on hand sufficient capital to further develop in parallel all three of these prospects.
Dr. Perlroth added, "Kodiak thanks the GLOW investigators and patients whose participation and commitment helped us to generate strong data in GLOW and thus to recognize the continued importance for patients of our ABC Platform and our platform-derived medicines."
About the GLOW Study Results
First time results from GLOW were presented at the American Academy of Ophthalmology retina subspecialty day on November 3, 2023. View original content: https://ir.kodiak.com/static-files/ee94e5bd-da6e-4038-b00c-1956c72e5c72.
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.
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.
GLOW also met all key secondary endpoints, including greater reductions in the proportion of patients developing sight-threatening complications (such as diabetic macular edema and proliferative diabetic retinopathy), versus sham, demonstrating an 89% decreased risk, achieving 21.0% versus 2.3% (p less than 0.0001). Tarcocimab also showed a 95% risk reduction in the development of DME, versus sham, from 13.7% on sham versus 0.7% on tarcocimab.
After the occurrence of a sight-threatening complication, all subjects were rescued with open-label tarcocimab, where subjects received two loading doses once monthly followed by continued every 12-week dosing. In patients developing sight-threatening complications, the initial visual acuity decrease and retinal anatomy worsening were both rapidly controlled and then stabilized with every 12-week dosing of tarcocimab.
The rates of serious ocular adverse events and intraocular inflammation in patients treated with tarcocimab and sham were similar in both groups.
About the GLOW Study Design
The Phase 3 GLOW study is a global, multi-center, randomized pivotal superiority study designed to evaluate the efficacy and safety of tarcocimab tedromer in treatment-naïve patients with moderately severe to severe NPDR. Patients are randomized to receive either tarcocimab every six months after initiating doses given at baseline, 8 weeks and 20 weeks into the study, or to receive sham injections. The primary endpoint is at one year. Outcomes include changes in diabetic retinopathy severity, measured on a standardized photographic grading scale, and the proportion of tarcocimab treated patients who developed a sight threatening complication due to diabetic retinopathy. Additional information about GLOW (also called Study KS301P106) can be found on www.clinicaltrials.gov under Trial Identifier NCT05066230 (https://clinicaltrials.gov/show/NCT05066230).
About the Primary Endpoint of ≥2-Step Improvement on the Diabetic Retinopathy Severity Scale (DRSS)
Derived from The Early Treatment Diabetic Retinopathy Study (ETDRS), the diabetic retinopathy severity scale (DRSS) is a systematic grading system developed to predict the risk of progression from NPDR to proliferative diabetic retinopathy (PDR). The DRSS characterizes retinopathy based on assessment of abnormalities in seven defined fields of fundus photographs. The scale divides diabetic retinopathy into levels ranging from absent to severe proliferative diabetic retinopathy. This scale is the most widely used standard for grading degrees of retinopathy in clinical studies.
About the Key Secondary Endpoint of Reducing Sight Threatening Complications
Approximately eight million people in the U.S. live with Diabetic Retinopathy (DR), a common complication of diabetes characterized by damage to the blood vessels in the retina. Diabetic retinopathy occurs when blood vessels in the retina are damaged by chronic high blood sugar levels caused by diabetes. DR is the leading cause of blindness among working-age American adults. The disease generally starts as NPDR and often has no warning signs or symptoms. Over time, patients with NPDR are at risk of suffering sight-threatening complications, including diabetic macular edema (DME), a swelling of the macula (the part of the retina responsible for central fine vision) and proliferative diabetic retinopathy (PDR) in which abnormal blood vessels grow on the surface of the retina and into the vitreous cavity. Sight-threatening complications can lead to severe vision loss in patients.