Kodiak Sciences Inc. has decided to reboot its tarcocimab tedromer clinical program following strong positive data from a phase 3 study assessing the candidate for treating diabetic retinopathy (DR).
Take note: this announcement follows the company’s announcement to halt the program in August 2023.
Lots to unpack here… start with this candidate.
KSI-301 (tarcocimab tedromer) is an investigational anti-vascular endothelial growth factor (VEGF) built on Kodiak’s antibody biopolymer conjugate (ABC) platform—designed to enable multi-mechanism therapies with durability and block all VEGF-A isoforms.
The candidate was previously in clinical trial testing for diabetic macular edema (DME) and was found to have a favorable safety profile and be well-tolerated in the following phase 3 trials:
- BEACON pivotal study (NCT04592419) for retinal vein occlusion (RVO)
- DAYLIGHT pivotal study (NCT04964088) for wet age-related macular degeneration (AMD)
Hold up. Didn’t the company discontinue testing on it?
Yes… but I can explain.
Earlier this year, the investigational candidate was being assessed in two identical phase 3 trials for DME: GLEAM (NCT04611152) and GLIMMER (NCT04603937).
However, in August 2023, the company announced that neither trials met their primary efficacy endpoint of non-inferior visual acuity (VA) gains for tarcocimab dosed every 8 to 24 weeks following 3 monthly loading doses (vs aflibercept every 8 weeks after 5 monthly loading doses).
What else went wrong?
While the candidate demonstrated strong durability—with half of the treated patients achieving every 24-week dosing at the primary endpoint—investigators noted, “an unexpected increase in cataract adverse events” reported over time in both trials.
This eventually led to the termination of both studies.
Gotcha. So how is there new data?
The prospective, randomized, double-masked, sham-controlled, two-arm, multicenter phase 3 GLOW study (NCT05066230) was launched in August 2021 and concluded in August 2023 (just a few weeks after the program was halted).
A total of 253 patients (ages 18+) were enrolled—all diagnosed with moderately severe to severe non-proliferative diabetic retinopathy (NPDR).
And what was evaluated?
The efficacy and safety of repeated 1:1 intravitreal dosing of KSI-301 (tarcocimab tedromer 5 mg) vs sham injection, with the following primary/secondary endpoints:
- Primary
- Proportion of eyes improving ≥2 steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) (Day 1 to Week 48).
- Secondary
- Proportion of eyes developing sight-threatening complications of DR such as DME, proliferative diabetic retinopathy (PDR), anterior segment neovascularization (ASNV). The timeframe was Day 1 to Week 48 and Week 96.
- See here for all secondary measures.
Now the findings.
In a turnaround from the GLEAM and GLIMMER trials for DME, the GLOW study met its 1-year primary endpoint for NPDR.
Per J. Pablo Velazquez-Martin, MD, Kodiak senior vice president of Clinical Science, tarcocimab significantly improved diabetic eye disease status and “significantly prevented sight-threatening complications.”
And the significance?
Dr. Velazquez-Martin also noted that this was the first time a 6-month dosing schedule in all patients was successful in treating DR, indicating a “meaningful and clinically relevant achievement” as well as its (and the ABC platform’s) durability potential for retinal vascular diseases.
See here for details on the study’s findings, presented by Charles C. Wykoff, MD, PhD, on behalf of the GLOW study group.
So what does this mean?
With three phase 3 pivotal trials now reporting success with tarcocimab for wet AMD, RVO, and NPDR, the company is moving toward the potential for a single Biologics License Application (BLA) submission for all three indications. “In recent discussions with the FDA, which included the GLOW data, we believe we have a clear regulatory pathway requiring one additional positive study,” stated Kodiak CEO Victor Perlroth, MD.
One more study?
Yup. The company has reportedly developed an updated formulation of tarcocimab—ready to be used in clinical trials—that improves usability via an injection time reduction from 7 to 10 seconds down to 2 to 3 seconds.
This formulation will be used in an upcoming trial that will be the final clinical data needed for that BLA submission.
So when will this study kick off?
No specific timeline has been released yet… so stay tuned for an update!