Kodiak Sciences released positive topline findings from its latest phase 3 clinical study evaluating Zenkuda (tarcocimab tedromer) for the treatment of diabetic retinopathy (DR).
First, a look at this candidate.
Zenkuda is an investigational anti-vascular endothelial growth factor (VEGF) under clinical development as a “mainstay” intravitreal (IVT) biologic monotherapy that provides:
- High efficacy and durability
- Based on its proprietary ABC platform (more on that in a moment)
- A flexible 1-month-through-6-month label
As Kodiak CEO Victor Perlroth, MD, noted: Zenkuda’s “enhanced commercial formulation” combines free (unconjugated) and conjugated protein in a single biologic.”
Tell me about its target patients.
These include patients diagnosed with retinal vascular disease—treatment-naïve, treatment-experienced, mild, and severe—including DR, retinal vein occlusion (RVO), and wet age-related macular degeneration (AMD).
- See here for background on these investigational indications.
Explain this ABC platform.
The biologics-based antibody biopolymer conjugate drug (ABCD) platform sits at the foundation of Kodiak's investigational therapy portfolio as a drug-engineering system.
What it does: Combines a targeting antibody (which binds VEGF in the eye) to a large, water-soluble biopolymer (attached to that antibody) to create a single, long-lasting therapeutic.
- See a step-by-step (and 3-D) look at this process.
A therapeutic such as Zenkuda?
Indeed. Aside from its durability, this therapeutic is capable of combining multiple modalities to target its target diseases (complex ocular and systemic included).
- See here for more on how the platform extends its ocular half-life to 20 days.
- And check out more on the company’s science of durability.
Now to its clinical data— what should we know?
We’ll focus solely on its DR indication (though Zenkuda has actually completed four phase 3 trials, including two for AMD).
The clinical study in question is GLOW2 (NCT06270836), a superiority, confirmatory trial designed to replicate and extend the findings from the original GLOW1 phase 3 study (NCT05066230).
To note: GLOW1 evaluated Zenkuda among patients with nonproliferative DR (NPDR).
- Its significance: This was the first time a 6-month dosing schedule in all participants was successful in treating DR (translating to the ABCD’s platform durability potential for retinal vascular diseases).
- See here for more on Zenkuda’s performance.
So … tell me more about GLOW2.
The difference between this registrational trial and GLOW1:
- The addition of an additional loading dose for greater flexibility
- A population extension to include three patient groups: moderately severe-and-severe DR, NPDR, and mild diabetic macular edema (DME)
- Click here for the full design and setup details.
- The enrolled study population included glucagon-like peptide (GLP-1) users
- 46.1% in the Zenkuda arm, 42.4% in the sham arm
And its outcome measures?
- 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:
- Eyes developing a sight-threatening complication of DR
- Eye improving ≥3 steps on DRSS from baseline at Week 48
Next up: this positive data.
We’ll start with the study meeting its primary endpoint: By Week 48, 62.5% of Zenkuda-treated patients achieved a ≥2-step improvement in DRSS score (versus 3.3% in the sham group; p< 0.0001).
How about the secondary outcomes?
Superiority was also demonstrated, with Zenkuda reducing the risk of developing prespecified sight-threatening complications (see here).
- The numbers: By 85% (versus 15.8% in the sham group, p = 0.001).
- And compare this to GLOW1’s 89% reduced risk.
Further: A total of 13.7% of Zenkuda-treated patients achieved a ≥3-step improvement in DRSS compared to 0% in the sham group (p < 0.0001).
- Compare that to GLOW1’s 5.6% and 0%, respectively.
… and how did those GLP-users fare?
A ≥2-step improvement in DRSS from baseline to Week 48 was achieved from baseline to Week 48 among:
- 60% of Zenkuda-treated patients
- 64.4% sham-treated patients
Let’s talk adverse events.
Per Kodiak, Zenkuda was well-tolerated—and only low rates (3.1% and under) of common ocular adverse events (AEs) were observed in 22% of treated patients’ study eye.
Among them: Dry eye, vitreous floaters, diabetic retinal edema, conjunctival hemorrhage, and DR.
Importantly: No cases of retinal vasculitis or occlusive retinal vasculitis were observed—along with no reports of intraocular inflammation (IOI), and a low incidence of cataract in the study eye (2.3% versus 1.6% for Zenkuda and sham, respectively, [and expected]).
This bodes well in supporting the ABCD Platform’s safety profile, according to Kodiak CEO Victor Perlroth, MD.
Nice! Now to the significance.
As Charles Wkyoff, MD, PhD, noted, GLOW2’s uniqueness as a DR approval-targeted registrational trial extends to its use of two key higher-risk populations: center-involved DME and PDR.
- “Zenkuda showed strong efficacy while incorporating a 6-month treatment interval after 3 monthly injections, supporting flexible dosing,” he stated.
Dr. Wykoff, chairman of Research, Retina Consultants of Texas, professor of Clinical Ophthalmology, and deputy chair of Ophthalmology at Blanton Eye Institute, Houston Methodist Hospital, will present the full end-of-study GLOW results at an upcoming (not specified) medical meeting.
So! What’s next for the company?
In light of the FDA’s recent pivot to a new single pivotal trial option for approvals, Kodiak is eyeing a potential expedited biologics license application (BLA) submission for two other candidates in its pipeline:
- KSI-501 for wet AMD
- Following a primary endpoint readout from the DAYBREAK study (NCT06556368)
- Expected: Q3 2026 (pending its success)
- Following a primary endpoint readout from the DAYBREAK study (NCT06556368)
- KSI-101 for macular edema secondary to inflammation (MESI)
- Following the PEAK study (NCT06990399) pivotal analysis 1 readout
- Expected: Q4 2026, if successful
- Following the PEAK study (NCT06990399) pivotal analysis 1 readout
See here for more details on these therapeutics.
But what about for Zenkuda—any FDA approval plans?
These plans appear to also include Zenkuda’s DR indication (though no specific timeframe has been provided). So you know what that means … stay tuned for developments later this year.