KSI-101 completes first pivotal cohort in phase 3 PEAK trial

Kodiak Sciences recently announced its completed enrollment of the first pivotal cohort in PEAK, a phase 3 trial evaluating the investigational bispecific biologic KSI-101 (tabirafusp alfa) in patients with macular edema secondary to inflammation (MESI), and reaffirmed that topline 24-week data from that cohort remain on track for December 2026.¹

MESI remains a leading cause of vision loss in patients with uveitis, and there is currently no intravitreal biologic approved specifically for the condition.¹ A positive, adequately controlled phase 3 readout would represent the first pivotal-scale test of dual interleukin-6 (IL-6) and VEGF inhibition delivered locally to the eye for inflammatory macular edema.

David A. Eichenbaum, MD, FASRS, one of the lead investigators of the trial, said KSI-101 could open treatment for MESI to many more patients and meaningfully change the treatment paradigm.

“If we see rapid and dramatic anatomical improvement—along with significant visual function increase—in these inflammatory macular edema patients, combined with a safety profile similar to our existing biologics, we will have a remarkable new, effective option for MESI with a safety profile superior to corticosteroid treatment,” he told the Eye Care Network.

Trial overview

PEAK (NCT06990399) is a randomized, double-masked, sham-controlled, multicenter phase 3 study with a planned enrollment of approximately 600 participants across 3 arms: intravitreal KSI-101 5 mg, KSI-101 10 mg, and sham injection.³ Patients receive fixed monthly dosing for 6 doses followed by individualized dosing through approximately week 44. The primary efficacy endpoint is mean change in best-corrected visual acuity (BCVA) from day 1 to the average of week 20 and week 24.³ Eligibility requires active or inactive non-infectious intraocular inflammation with central subfield thickness of at least 400 µm and baseline BCVA between 20/40 and 20/320; eyes with edema attributable to diabetic retinopathy, retinal vein occlusion, or age-related macular degeneration are excluded.³

According to the company, the roughly 300 patients currently enrolled constitute the first cohort supporting the trial's initial pivotal analysis, with a second analysis planned across approximately 600 patients pooled from PEAK and the companion PINNACLE trial (NCT06996080), which enrolls patients with milder disease.^1,4 Kodiak reaffirmed that topline data from the first pivotal analysis are expected in December 2026, with the second analysis anticipated in the second quarter of 2027.¹ Chief executive officer Victor Perlroth said completion of enrollment allowed the company to "confidently plan for the topline data to be released in December 2026."¹

Clinical context and unmet need

Macular edema is the most common structural cause of vision impairment in uveitis. Standard management relies on controlling intraocular inflammation with corticosteroids—delivered by intravitreal injection or sustained-release implants such as the dexamethasone and fluocinolone acetonide implants—and, in many patients, systemic immunomodulatory therapy.⁵⁶ Adalimumab remains the only biologic with regulatory approval for non-infectious intermediate, posterior, and panuveitis, and it acts on tumor necrosis factor rather than directly on the IL-6 or VEGF pathways implicated in edema.⁵⁷ Corticosteroid-based approaches, while effective, carry well-recognized risks of cataract progression and elevated intraocular pressure, underscoring interest in steroid-sparing, pathway-targeted alternatives.⁶

Drug background

KSI-101 is an investigational bispecific biologic engineered to inhibit both IL-6—a cytokine central to inflammatory vascular leakage—and VEGF, a principal driver of vascular permeability.² It is the higher-strength (100 mg/mL) member of a bispecific program that also includes KSI-501, an antibody biopolymer conjugate that Kodiak is developing for retinal vascular diseases such as diabetic macular edema and neovascular age-related macular degeneration.² The rationale for dual blockade in MESI is that inflammatory and vascular-permeability pathways jointly contribute to fluid accumulation in the macula.

Supporting phase 1b evidence comes from the open-label APEX study, in which the MESI cohort was treated across 2.5-mg, 5-mg, and 10-mg dose groups of 13 patients each. Reported mean BCVA gains were 13.4 letters in the 5-mg group and 15.4 letters in the 10-mg group by week 20, and at least 90% of patients across doses achieved absence of intraretinal and subretinal fluid, with reductions in central subfield thickness of roughly 150 to 230 µm and a favorable early safety profile.⁴⁸

Interpretation and limitations

The APEX signal is encouraging but should be read with caution. The MESI cohorts were small, open-label, and uncontrolled, and short-term anatomic drying and letter gains do not by themselves establish durable, clinically meaningful benefit or a fully characterized safety profile. PEAK's randomized, sham-controlled, masked design directly addresses those weaknesses and is the appropriate test of efficacy. Because MESI encompasses a heterogeneous population—varied uveitis etiologies and both active and quiescent inflammation—generalizability across subgroups, durability beyond the individualized-dosing phase, and comparative performance against corticosteroid standards will remain open questions even with a positive readout. The December 2026 disclosure will report the 24-week primary endpoint for the first cohort only; the pooled second pivotal analysis and longer-term follow-up will be needed to fully judge the therapy's role, and regulatory review lies beyond these datasets.¹³

References

1. Kodiak Sciences Completes Enrollment in First Pivotal Cohort in the Phase 3 PEAK Trial of KSI-101 for Macular Edema Secondary to Inflammation and Reaffirms Topline Clinical Data Release Remains on Track for December 2026. PR Newswire. August 6, 2026. https://www.prnewswire.com/news-releases/kodiak-sciences-completes-enrollment-in-first-pivotal-cohort-in-the-phase-3-peak-trial-of-ksi-101-for-macular-edema-secondary-to-inflammation-and-reaffirms-topline-clinical-data-release-remains-on-track-for-december-2026-302844806.html

2. Our Pipeline. Kodiak Sciences. Accessed August 18, 2026. https://kodiak.com/our-pipeline/

3. A Phase 3 Study to Evaluate the Efficacy and Safety of Intravitreal Tabirafusp Alfa (KSI-101) in Participants With Macular Edema Secondary to Inflammation (MESI) — PEAK. ClinicalTrials.gov identifier: NCT06990399. Accessed August 18, 2026. https://clinicaltrials.gov/study/NCT06990399

4. A Phase 3 Study to Evaluate the Efficacy and Safety of Intravitreal KSI-101 in Participants With Macular Edema Secondary to Inflammation (MESI) — PINNACLE. ClinicalTrials.gov identifier: NCT06996080. Accessed August 18, 2026. https://clinicaltrials.gov/study/NCT06996080

5. Fabiani C, et al. Update on non-infectious uveitis treatment: anti-TNF-alpha and beyond. Front Ophthalmol. 2024. https://www.frontiersin.org/journals/ophthalmology/articles/10.3389/fopht.2024.1412930/full

6. Pharmacotherapy for non-infectious uveitis: spotlight on phase III clinical trials of locally injected or implanted therapeutics and systemic immunomodulatory drugs. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC12141190/

7. A systematic review and economic evaluation of adalimumab and dexamethasone for treating non-infectious intermediate uveitis, posterior uveitis or panuveitis in adults. Health Technol Assess. 2017. PubMed. https://pubmed.ncbi.nlm.nih.gov/29183563/

8. Kodiak Sciences releases follow-up, 20-week data from APEX study. Ophthalmology Times. https://www.ophthalmologytimes.com/view/kodiak-sciences-releases-follow-up-20-week-data-from-apex-study