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KODIAK: KSI-301 Wet AMD Phase 2b/3 Study Summary

Core Content

KODIAK is an ophthalmology medicines company that has conducted a Phase 2b/3 study evaluating KSI-301, a novel biologic designed to enhance durability and extend dosing intervals for patients with retinal vascular diseases. The study focused on wet age-related macular degeneration (AMD), comparing KSI-301 with aflibercept, a commonly used treatment.

Key Information

Study Design

• KSI-301: Administered every 12 to 20 weeks (Q12W-Q20W)
• Aflibercept: Administered every 8 weeks (Q8W)
• The study was randomized, multicenter, and involved 277 KSI-301 and 280 aflibercept patients.
• The primary endpoint was non-inferiority in BCVA (Best Corrected Visual Acuity) change from baseline.

Patient Demographics

• Gender: 64.3% female in KSI-301 group vs. 60.0% in aflibercept group.
• Age: Mean age of 76.6 years in KSI-301 group vs. 76.2 years in aflibercept group.
• Geographical Region: 82.7% of KSI-301 patients were from the USA vs. 83.9% for aflibercept.
• Ethnicity and Race: The groups were well-balanced, with a majority of non-Hispanic or Latino White patients.

Baseline Ocular Characteristics

• BCVA (ETDRS Letters): Mean of 63.6 in both groups.
• CST (Central Subfield Thickness): Mean of 350.4 μm for KSI-301 vs. 359.5 μm for aflibercept.
• Intraretinal fluid: 43.7% of KSI-301 patients had visible fluid vs. 38.9% for aflibercept.
• Subretinal fluid: 80.9% of KSI-301 patients had visible fluid vs. 82.5% for aflibercept.
• Intraocular Pressure: Mean of 15.1 mmHg for KSI-301 vs. 14.6 mmHg for aflibercept.

Main Findings

Primary Endpoint Not Met

• Non-inferiority in BCVA was not demonstrated for KSI-301 compared to aflibercept.
• The majority of KSI-301-treated patients achieved durable visual gains, but the impact of undertreatment in some patients is believed to be the reason for the failure to meet the primary endpoint.

Durability

• 60% of KSI-301 patients were on Q20W dosing at Year 1.
• 59.4% on Q20W and 69.7% on ≥ Q16W achieved meaningful reductions in CST and vision improvements comparable to aflibercept.
• Durability was observed in most patients, with visual acuity gains comparable to the aflibercept group.

Safety

• KSI-301 was safe and well-tolerated.
• Intraocular inflammation occurred in 3.2% of KSI-301 patients, which is within the reported range for aflibercept (1 - 4.5%).
• No cases of intraocular inflammation with vascular occlusion were observed.
• Treatment-emergent adverse events (TEAEs) were more common in the KSI-301 group, possibly due to undertreatment in some patients.

Discontinuation

• A greater number of discontinuations occurred in the KSI-301 group, mainly due to undertreatment events.

Key Points

• KSI-301 is a conjugate of an IgG1 antibody and a biopolymer, designed for ocular durability and extended dosing intervals.
• The ABC Platform is intended to enhance treatment durability and reduce the frequency of injections.
• KSI-301 showed robust durability in patients who could be treated every 20 weeks, but some patients required more frequent dosing.
• Safety was a strong point, with low rates of intraocular inflammation and no serious adverse events related to the treatment.
• Undertreatment was a significant factor in the failure to meet the primary endpoint, as more frequent dosing was not allowed under the protocol.

Comparison with Other Indications

Conclusion

The Phase 2b/3 study of KSI-301 in wet AMD showed durable visual gains and good safety profile, but failed to meet the primary endpoint of non-inferiority in BCVA. This was attributed to undertreatment in some patients, as more frequent dosing was not permitted under the study protocol. Despite this, KSI-301 demonstrated potential for extended dosing intervals and improved patient outcomes, suggesting its value in reducing the burden of frequent injections. Further studies are needed to optimize dosing regimens and confirm long-term efficacy and safety.