- Topline clinical data of the confirmatory registrational study GLOW2 expected in 1Q 2026.
- GLOW2 study design mirrors GLOW1 study, which met primary endpoint and all key secondary endpoints with high statistical significance
Kodiak Sciences Inc. (Nasdaq: KOD), today announced that it has completed enrollment in its GLOW2 phase 3 clinical trial of tarcocimab tedromer in patients with diabetic retinopathy (DR).
"We randomized more than 250 patients into our GLOW2 phase 3 study, exceeding our enrollment target," said Victor Perlroth, MD, CEO of Kodiak. "With its 48-week duration of treatment, all patients are expected to complete their primary endpoint visits by the end of January 2026, and we expect to announce topline clinical data in 1Q 2026."
"The GLOW2 design mirrors that of our successful GLOW1 study, with the advantage of an additional loading dose to provide dosing flexibility for providers. GLOW2 is our second registrational study in (DR) and if there is a successful outcome, we anticipate having a regulatory package for tarcocimab that is ready to file. We remain focused on completing enrollment in our ongoing DAYBREAK phase 3 study to broaden the efficacy profile for tarcocimab in wet age-related macular degeneration (wet AMD), and it is our plan to wait for DAYBREAK topline data expected in 2Q 2026 in order to file a single BLA for tarcocimab in wet AMD, DR and Retinal Vein Occlusion ("RVO")," concluded Dr. Perlroth.
Dr. Allen Hu, top enroller in the GLOW2 study and principal investigator at Cumberland Valley Retina Consultants commented on tarcocimab's potential in DR. "Fewer than 1% of subjects with (DR) are treated today due to high treatment burden associated with frequent injections needed with today's approved therapies. If diabetic retinopathy is left untreated, the majority of patients —and this is millions of patients— will experience disease progression and develop vision-threatening complications. With only 4 doses in Year 1 and every 6-month dosing in every patient, the GLOW1 data showed us as a community that tarcocimab can potentially achieve strong efficacy both in treating existing disease and preventing disease progression in (DR)."
"If GLOW2 mirrors these results, I believe tarcocimab as a biologic with twice yearly dosing in all patients can change the treatment landscape in (DR) and help millions of patients," concluded Dr. Hu.
About the phase 3 GLOW2 study
The phase 3 GLOW2 study is a prospective, randomized, double-masked, multi-center pivotal superiority study designed to evaluate the efficacy and safety of tarcocimab tedromer in treatment-naïve patients with DR.
Patients are randomized 1:1 and receive either sham injections or tarcocimab via intravitreal injection at baseline, Week 4, Week 8, Week 20 and Week 44.
The primary endpoint is the proportion of eyes improving ≥2 steps on Diabetic Retinopathy Severity Scale ("DRSS") from baseline at Week 48. Additional outcome measures include the proportion of eyes developing a sight threatening complication of DR and the proportion of eyes improving ≥3 steps on DRSS from baseline at Week 48. Additional information about GLOW2 (also called Study KS301P108) can be found on www.clinicaltrials.gov under Trial Identifier NCT06270836 (https://clinicaltrials.gov/show/NCT06270836).
About tarcocimab tedromer (tarcocimab, KSI-301)
Tarcocimab is an investigational anti-VEGF therapy built on Kodiak's proprietary Antibody Biopolymer Conjugate (ABC) Platform and is being developed as a "mainstay" intravitreal biologic monotherapy intended to provide high efficacy and high durability and a flexible 1-month through 6-month label.
To date, tarcocimab has completed three successful phase 3 pivotal clinical studies: the phase 3 GLOW1 study in DR, the phase 3 BEACON study in retinal vein occlusion (RVO) and the phase 3 DAYLIGHT study in wet AMD.
In the GLOW1 study, tarcocimab successfully treated DR patients and prevented disease progression with 100% of patients on extended 6-month dosing.
In the BEACON study, in the first 6 months tarcocimab-treated patients were dosed on every 8-week interval and in the second 6 months nearly half of tarcocimab patients did not require any treatment while achieving similar vision and anatomical outcomes as the aflibercept group at one year.
Tarcocimab is currently being studied in two phase 3 clinical trials, the GLOW2 study in DR and the DAYBREAK study in wet AMD.
The GLOW2 study has a similar design as GLOW1 in which all patients randomized to investigational therapy will receive tarcocimab on extended, 6-month dosing. GLOW2 features the benefit of an additional, third monthly loading dose (baseline, Week 4, Week 8) to explore even further benefits with tarcocimab in DR patients.
The DAYBREAK study includes tarcocimab in a second investigational arm against active comparator aflibercept and incorporates learnings from prior pivotal trials of tarcocimab to maximize the probability of meeting the primary endpoint of non-inferiority in visual acuity gains. Patients randomized to tarcocimab will receive individualized dosing every 4 to 24 weeks on an as needed basis following four monthly loading doses. Patients randomized to aflibercept will be dosed per its label.
The individualized dosing of tarcocimab is determined by a treat-to-dryness proactive approach, using presence of retinal fluid as a disease activity marker, which resembles retina specialists' practice and optimizes each patient's treatment, instead of a combination of central subfield thickness ("CST") and vision loss. The objectives for tarcocimab in DAYBREAK are to assess its 6-month durability potential, strengthen its competitive position in wet AMD and bolster the regulatory application package for the program.
Both GLOW2 and DAYBREAK use tarcocimab's enhanced 50 mg/mL formulation containing both conjugated and unconjugated antibody that is intended to balance immediacy and durability. DAYBREAK is actively enrolling patients. Additional information about GLOW2 can be found on www.clinicaltrials.gov under Trial Identifier NCT06270836 (https://clinicaltrials.gov/study/NCT06270836). Additional information about DAYBREAK can be found on www.clinicaltrials.gov under Trial Identifier NCT06556368 (https://clinicaltrials.gov/study/NCT06556368).
About diabetic retinopathy and tarcocimab
DR is a common complication of diabetes that affects the eye. If left untreated, DR progresses and eventually can lead to serious vision-threatening complications, such as diabetic macular edema and proliferative diabetic retinopathy. It is estimated that of the 36 million American adults living with diabetes, approximately 10 million have diabetic retinopathy and fewer than 1% will choose to be treated with today's available medicines due to the high treatment burden associated with frequent injections.
Long interval dosing is particularly important in the DR population, and our GLOW1 and GLOW2 studies are designed to explore the ability of tarcocimab, with all patients on an every 6-month dosing interval, to directly improve the disease (the primary endpoint) and to prevent vision threatening complications from the worsening of the disease (key secondary endpoint).
At one year, GLOW1 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-value less than 0.0001). Visual acuity and retinal anatomy were improved and stable with tarcocimab on its extended-dosing intervals.
GLOW1 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 DR), versus sham, demonstrating an 89% decreased risk, achieving 21.0% versus 2.3% (p-value 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.