First patients treated in Phase 3 GLOW2 study of tarcocimab tedromer in diabetic retinopathy from Kodiak Sciences

(Image Credit: AdobeStock/ipopba)

Kodiak Sciences Inc. announced the first patients with diabetic retinopathy (DR) have been treated in the randomized double masked Phase 3 GLOW2 study of tarcocimab tedromer.

According to a news release, GLOW2 (NCT06270836) is the second Phase 3 study of tarcocimab in diabetic retinopathy in which all patients on investigational therapy will receive tarcocimab on extended dosing intervals, including 6-month dosing for all patients.¹

The company noted the GLOW2 study follows its GLOW1 study in which tarcocimab-treated patients, over the 48-week study duration, saw 29-fold increased response rate in ≥ 2-step improvement in DRSS (treatment) and 89% decreased risk of developing sight-threatening complications (prevention).

Kodiak runs 6 pivotal studies in parallel for the tarcocimab program, and it noted GLOW2 is on an accelerating trajectory of site activations, new patient screenings and randomizations with the goal to complete enrollment before the end of this year.

Victor Perlroth, MD, Kodiak's CEO, noted it has been uphill climb in the race to develop a long-acting retinal therapy, with mixed treatment and prevention results in diabetic retinopathy.

“GLOW1 data showed unequivocally that treatment with tarcocimab in extended dosing intervals including 6-month dosing in all patients achieved two related but clinically distinct goals: treating existing disease (primary endpoint of 2-step improvement in DRSS) and preventing disease progression (key secondary endpoint of preventing sight-threatening complications),” Perlroth said in a news release. “This is a key differentiator in the long-acting therapy space, where many therapies are only designed to maintain a patient's current disease status and not to improve it."

If successful, GLOW2 could serve as 1 of the 2 successful pivotal studies in one foundational indication, diabetic retinopathy, to support marketing authorization application for tarcocimab.

The Phase 3 GLOW2 study is a prospective, randomly assigned, double-masked, multi-center pivotal superiority study designed to evaluate the efficacy and safety of tarcocimab tedromer in treatment-naïve patients with diabetic retinopathy (DR). The company noted in its news release that patients are randomized 1:1 and receive 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 diabetic retinopathy and the proportion of eyes improving ≥ 3 steps on DRSS from baseline at Week 48.

According to the company, tarcocimab is an investigational anti-VEGF therapy built on Kodiak's proprietary antibody biopolymer conjugate (ABC) platform and is designed to maintain potent and effective drug levels in ocular tissues for longer than existing available agents.

Moreover, the company noted its goal with tarcocimab is to enable earlier treatment and prevention of vision loss for patients with diabetic retinopathy and to develop a new durability agent to improve outcomes for patients with retinal vascular diseases.

To date, tarcocimab has completed 3 successful Phase 3 pivotal clinical studies: the Phase 3 GLOW1 study in diabetic retinopathy, the Phase 3 BEACON study in retinal vein occlusion, and the Phase 3 DAYLIGHT study in wet AMD.

Kodiak noted in the news release, it is initiating 2 additional BLA-facing Phase 3 studies: the GLOW2 study in diabetic retinopathy, and the DAYBREAK study in wet AMD. The GLOW2 study has a similar design as GLOW1 with the benefit of an additional, third monthly loading dose (weeks 0, 4 and 8). The DAYBREAK study will include investigational arms for tarcocimab and KSI-501, Kodiak's bispecific conjugate, to evaluate their efficacy, safety and durability versus aflibercept. DAYBREAK is designed to strengthen the competitive position of tarcocimab in wet AMD and bolster the ex-US regulatory dossier for the program.¹

Company officials said both GLOW2 and DAYBREAK will use a go-to-market formulation of tarcocimab. GLOW2 is actively enrolling patients, and we are operationalizing towards DAYBREAK study activation in mid-2024.

In November 2023, Kodiak announced its Phase 3 GLOW superiority study evaluating tarcocimab tedromer 5 mg in moderately severe to severe non-proliferative diabetic retinopathy (NPDR) met its 1-year primary, and all key secondary endpoints.²

At that time, the company announced that it would be “rebooting” the tarcocimab tedromer development program.

References:

1. Inc KS. Kodiak Sciences Announces Treatment of First Patients in Phase 3 GLOW2 Study of Tarcocimab Tedromer in Diabetic Retinopathy. www.prnewswire.com. Accessed May 14, 2024. https://www.prnewswire.com/news-releases/kodiak-sciences-announces-treatment-of-first-patients-in-phase-3-glow2-study-of-tarcocimab-tedromer-in-diabetic-retinopathy-302144051.html

2. Kodiak reboots tarcocimab tedromer development program following strong positive results in Phase 3 diabetic retinopathy GLOW study and following dialogue with US regulatory authorities on a regulatory pathway for BLA submission. Press Release. Released November 6, 2023. Accessed November 6, 2023. https://ir.kodiak.com/news-releases/news-release-details/kodiak-reboots-tarcocimab-tedromer-development-program-following