Kodiak Sciences Completes Enrollment in First Pivotal Cohort of Phase 3 PEAK Trial for KSI-101 in Macular Edema Secondary to Inflammation
核心洞察
Kodiak Sciences has completed enrollment of the first 300-patient cohort in the Phase 3 PEAK trial of KSI-101 for macular edema secondary to inflammation (搜索) (MESI), with topline data expected in December 2026.
KSI-101 is a novel bispecific protein targeting both IL-6 and VEGF (搜索), and there are currently no approved intravitreal biologic therapies for the spectrum of MESI diseases.
Phase 1b APEX data showed robust efficacy, with more than half of patients achieving ≥15-letter gains in best corrected visual acuity and over 90% resolution of intraretinal and subretinal fluid by Week 8.
Kodiak Sciences Inc. (Nasdaq: KOD) has completed enrollment of the first 300-patient cohort in its Phase 3 PEAK trial, marking a critical milestone for the KSI-101 registrational program in macular edema secondary to inflammation (搜索) (MESI). The Palo Alto-based, retina-focused biotechnology company also reaffirmed that topline clinical data from Pivotal Analysis 1, evaluating the 24-week primary endpoint, remains on track for release in December 2026.
"We were pleased to complete this important enrollment milestone in early June, and we can now confidently plan for the topline data to be released in December 2026," said Victor Perlroth, M.D., Chief Executive Officer of Kodiak. "Our data from the Phase 1b APEX study meaningfully increased our conviction in KSI-101's potential to be a cornerstone therapy for MESI patients. The global registrational PEAK trial is the first pivotal test of that conviction, and we look forward to sharing topline data before the end of this year."
An Unmet Need in Retinal Disease
MESI represents a heterogeneous group of diseases characterized by macular edema and visual impairment driven by a common pathophysiology of inflammation and blood retinal barrier disruption. The condition encompasses a broad range of etiologies, including autoimmune-associated, idiopathic, post-procedural, and inflammatory choroidal neovascularization, irrespective of the anatomical location of inflammation within the eye.
Currently, no intravitreal biologic therapies are approved to address the spectrum of MESI diseases. Existing treatment options remain limited by side effects and tolerability concerns, underscoring the need for safer and more effective alternatives. MESI represents a new macular edema market segment distinct from the established anti-VEGF (搜索) market.
"Many of these patients have experience with corticosteroid use and understand its limitations, including the risks of elevated intraocular pressure and cataract," said David Eichenbaum, M.D., Director of Research at Retina Vitreous Associates of Florida and a principal investigator in the PEAK and PINNACLE clinical trials. "I am encouraged by the data generated to date with KSI-101 in which the therapy appears to work well and to date is demonstrating a favorable safety profile."
KSI-101: Dual-Targeting Bispecific Protein
KSI-101 is a novel, potent bispecific protein formulated at high strength (100 mg/mL) that targets both IL-6 and VEGF (搜索). Data from the dose-finding Phase 1b APEX study demonstrated robust anatomical and visual responses across MESI patients. More than half of patients achieved ≥15-letter gains in best corrected visual acuity, with additional benefit observed at higher dose levels.
Rapid vision improvements were documented, with 10-letter gains by Week 4 in top dose groups and OCT central subfield thickness below 325 microns achieved as early as Week 1. Continued anatomical improvement was observed over time, with greater than 90% resolution of intraretinal fluid (IRF) and subretinal fluid (SRF) by Week 8, and 20/25 Snellen visual acuity achieved by Week 20. In top dose groups, at least 90% of patients achieved complete absence of IRF and SRF, indicating retinal dryness and normalization of retinal architecture. KSI-101 was well tolerated with a favorable safety profile throughout the study.
PEAK and PINNACLE Trial Design
The PEAK and PINNACLE studies are superiority trials evaluating two dose levels of KSI-101 (5 mg and 10 mg) compared to sham treatment in patients with MESI. While identical in study design, the two trials differ in patient populations: PEAK enrolls patients with more severe disease (moderate to severe macular edema and vision impairment), while PINNACLE includes patients with milder disease as well as those with moderate to severe macular edema who retain good vision.
Patients randomized to KSI-101 treatment arms receive fixed monthly dosing for six doses (Day 1 to Week 20), followed by individualized dosing for six additional visits (Week 24 to Week 44). Patients in the sham arm receive monthly sham dosing for six doses followed by sham as needed. The primary and key secondary endpoints will be evaluated at Week 24.
"Pivotal Analysis 1 gives us the opportunity to evaluate KSI-101 in patients with more severe MESI across our global site footprint," said J. Pablo Velazquez-Martin, M.D., Chief Medical Officer of Kodiak. "These are patients at high risk of losing meaningful vision, and the goal of treatment is not only to reduce inflammation but to dry the retina and improve vision without the toxicities and other limitations associated with today's complex patchwork of systemic and ocular therapies."
Upcoming Milestones
Completion of enrollment in the second pivotal cohort, evaluating 600 subjects across the PEAK and PINNACLE studies, is expected in the fourth quarter of 2026, with topline clinical data anticipated in the second quarter of 2027. Kodiak Sciences is also advancing two additional late-stage clinical programs: Zenkuda (tarcocimab tedromer), which has a BLA-ready profile in diabetic retinopathy, retinal vein occlusion, and wet AMD, and KSI-501, both being explored in the Phase 3 DAYBREAK wet AMD study with topline data expected in September 2026.