The Phase 3 Registration STAR Study of Efdamrofusp Alfa (IBI302) Met its Primary Endpoint, Making it the First Self-developed Extended-interval Treatment for nAMD in China

STAR (NCT05972473) is a Phase 3 clinical study evaluating the efficacy and safety of IB302 8 mg in Chinese participants with nAMD. A total of 600 participants were randomized in a 1:1 ratio to the IBI302 8 mg group and the aflibercept 2 mg group. Both groups received 3 loading doses administered every 4 weeks. After the completion of the loading doses, participants in the IBI302 8 mg group were administered at Q16W, Q12W, or Q8W intervals based on the disease activity assessment at Weeks 16 and 20. Participants in the aflibercept 2 mg group completed the subsequent treatment at Q8W intervals. The study lasts for 100 weeks, and the primary endpoint is the change from baseline in the best corrected visual acuity (BCVA) of the study eye at Week 52. The randomization stratification factors in this study were: the presence or absence of Type 2 choroidal neovascularization (CNV) on optical coherence tomography (OCT) in the study eye, and whether the study eye had previously received anti-VEGF treatment.

The study enrolled 600 participants (including 65% treatment-naïve participants) with a baseline mean BCVA of 58.1 ETDRS letters and a baseline mean central subfield thickness (CST) of 420.75 μm.

The study results showed that in nAMD patients receiving IBI302 8 mg,

• Visual acuity improvement non-inferior to aflibercept: The study met the primary endpoint. At Week 52, the least squares mean estimate (SE) of the mean BCVA change from baseline in the IBI302 8 mg and aflibercept 2 mg groups was 10.37 (0.547) and 10.11 (0.545) ETDRS letters, respectively.
• Extension of dosing interval: Approximately 86% of participants in the IBI302 8 mg group achieved a dosing interval of Q12W or above during the maintenance period; 72.8% of participants achieved a dosing interval of Q16W. At Week 52, approximately 95% of the participants receiving the Q12/16W dosing maintained their interval without requiring retreatment. Furthermore, 56.3% of the participants showed no disease activity at Week 24, demonstrating the potential to extend the dosing interval to Q20W.

Table 1. Dosing intervals in Phase 3 trials of efdamrofusp alfa and faricimab (cross-trial indirect comparison)

• Improvement in anatomical efficacy endpoints: The proportion of participants with no intraretinal fluid and no subretinal fluid in the fovea at Week 16 was comparable between the two groups, and the improvements from baseline in the change in CST from baseline and other anatomical endpoints were similar at Week 52.
• Potential to inhibit macular atrophy (MA): At Week 52, the incidence of MA in the IBI302 8 mg group and aflibercept 2 mg group was 1.5% and 2.9%, respectively. The incidence of MA after IBI302 treatment was 50% lower than that in the aflibercept group, and the trend was consistent with the results of Phase 2 studies, suggesting that IBI302 has the potential to inhibit MA.
• Favorable safety: The overall incidence of AEs in the IBI302 8 mg group were comparable to those in the aflibercept 2 mg group. Most ocular adverse events were mild to moderate and resolved after observation or routine management.

The follow-up of this study is still ongoing, and the complete data will be published in future academic conferences or peer-reviewed academic journals.

Professor Xiaodong Sun, Principal Investigator of the Study, Director of the Eye Center, Deputy Director of National Center for Clinical Ophthalmology, Deputy Director of Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, stated: " As the Principal Investigator, I am delighted to witness the outstanding performance of IBI302 in the STAR study. Although anti-VEGF agents are the first-line therapy for nAMD, the requirement for frequent intravitreal injections and follow-up visits severely compromises patient adherence and quality of life. A key direction in current drug development is exploring multi-target therapeutic strategies and achieving extended dosing intervals to alleviate the treatment burden on patients. As the world's first innovative anti-VEGF/anti-complement dual-target molecule, IBI302 met the primary endpoint in the Phase 3 STAR study, demonstrating non-inferiority to aflibercept in vision improvement (an average gain of approximately 10.37 letters). Furthermore, most participants were able to achieve a personalized dosing interval of every 12 weeks or longer. Notably, over 70% of these patients could maintain a 16-week dosing interval, significantly reducing the number of injections. This is the first domestically developed novel anti-VEGF fusion protein for ophthalmic use in China to demonstrate the capability of a 16-week dosing interval in a Phase 3 study. We also observed the potential of IBI302 in reducing the incidence of new-onset macular atrophy. We look forward to the timely regulatory approval of this innovative therapy, bringing an alternative treatment option to nAMD patients in China and worldwide. The 2-year results will also be continuously observed to explore the effect on MA inhibition"

Dr. Lei Qian, Chief R&D Officer of General Biomedicine of Innovent, stated, "We are delighted that our innovative ophthalmic drug candidate, efdamrofusp alfa, has achieved a breakthrough in the Phase 3 STAR study. Efdamrofusp alfa demonstrated vision improvement comparable to aflibercept and enabled over 70% of participants to maintain a personalized dosing interval of every 16 weeks, significantly alleviating the treatment burden on patients. Concurrently, the study observed that efdamrofusp holds a potential advantage in inhibiting macular atrophy. These encouraging results lay a solid foundation for subsequent development. We will actively prepare to submit a New Drug Application (NDA), striving to provide a more convenient, patient-friendly, and highly efficacious treatment option for nAMD patients as early as possible. Meanwhile, we will comprehensively advance the lifecycle management and strategic layout of our ophthalmic products, focusing on therapies with a faster onset of action, more durable efficacy, and superior long-term treatment benefits (such as lowering the incidence of macular atrophy and achieving a more complete resolution of retinal edema). Our goal is to bring a greater number of high-quality, innovative ophthalmic drugs to the vast population of patients with nAMD and other fundus diseases."

About Efdamrofusp Alfa (IBI302)

IBI302 is a recombinant fully human bispecific fusion protein of Innovent Biologics with global proprietary rights. The N- terminal is a VEGF domain that can bind to the VEGF family, block VEGF-mediated signaling pathway, inhibit vascular epithelium proliferation and angiogenesis, and improve vasopermeability and reduce leakage. The C- terminal of IBI302 is the complement binding domain that can inhibit the activation of the classic pathway and alternative pathway of complement through the specific binding of C3b and C4b, and reduce the inflammatory response mediated by the complement. IBI302 may exert its therapeutic effect by inhibiting both VEGF-mediated angiogenesis and complement activation pathways.

About Innovent Biologics

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 18 products in the market. It has 5 assets in Phase 3 or pivotal clinical trials and 14 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Lilly, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action" Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

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