Bispecific vs. Bispecific: Innovent Announces First Patient Dosed in the Phase 2 Clinical Study of Efdamrofusp Alfa (IBI302), a First-in-class Anti-VEGF and Anti-Complement Bispecific Fusion Protein for the Treatment of Diabetic Macular Edema
Studi clinici precedenti hanno evidenziato che l'efdamrofusp alfa ad alta dose (8 mg) migliora significativamente l'acuità visiva e l'edema retinico, con la possibilità di estendere gli intervalli di somministrazione a 12-16 settimane. Il farmaco mira a superare i limiti delle terapie attuali per il DME, che richiedono iniezioni frequenti ogni 4-8 settimane.
Il mercato potenziale è rilevante, considerando che in Cina ci sono oltre 140 milioni di pazienti diabetici, di cui circa un terzo sviluppa retinopatia diabetica. Il tasso di prevalenza del DME tra questi pazienti varia dal 7% al 14%, stimando così un numero di 4-5 milioni di pazienti con DME in Cina.
Estudios clínicos previos han demostrado que la dosis alta (8 mg) de efdamrofusp alfa mejora significativamente la agudeza visual y el edema retiniano, con potencial para extender los intervalos de dosificación a 12-16 semanas. El medicamento busca superar las limitaciones de los tratamientos actuales para el DME, que requieren inyecciones frecuentes cada 4-8 semanas.
La oportunidad de mercado es considerable, ya que en China hay más de 140 millones de pacientes diabéticos, de los cuales aproximadamente un tercio desarrolla retinopatía diabética. La prevalencia de DME entre estos pacientes varía del 7% al 14%, estimando así entre 4 y 5 millones de pacientes con DME en China.
이전 임상 연구에서 고용량(8mg) efdamrofusp alfa는 시력과 망막 부종을 크게 개선했으며, 투약 간격을 12~16주로 연장할 가능성이 있음을 보였습니다. 이 약물은 현재 DME 치료가 4~8주마다 자주 주사해야 하는 한계를 극복하는 것을 목표로 합니다.
시장 기회도 큽니다. 중국에는 1억 4천만 명 이상의 당뇨병 환자가 있으며, 그 중 약 3분의 1은 당뇨병성 망막병증을 앓고 있습니다. 이 환자들 중 DME 유병률은 7%에서 14% 사이로, 중국 내 DME 환자는 약 400만에서 500만 명으로 추산됩니다.
Des études cliniques antérieures ont montré que la dose élevée (8 mg) d'efdamrofusp alfa améliore significativement l'acuité visuelle et l'œdème rétinien, avec un potentiel d'extension des intervalles de dosage à 12-16 semaines. Le médicament vise à surmonter les limites des traitements actuels du DME, qui nécessitent des injections fréquentes toutes les 4 à 8 semaines.
Le potentiel de marché est important, la Chine comptant plus de 140 millions de patients diabétiques, dont environ un tiers développent une rétinopathie diabétique. Le taux de prévalence du DME parmi ces patients varie de 7 % à 14 %, ce qui suggère un nombre estimé de 4 à 5 millions de patients atteints de DME en Chine.
Frühere klinische Studien zeigten, dass die Hochdosis (8 mg) von efdamrofusp alfa signifikante Verbesserungen der Sehschärfe und des Netzhautödems bewirkt, mit der Möglichkeit, die Dosierungsintervalle auf 12-16 Wochen zu verlängern. Das Medikament zielt darauf ab, die Einschränkungen der aktuellen DME-Behandlungen zu überwinden, die häufige Injektionen alle 4-8 Wochen erfordern.
Der Markt ist groß: In China gibt es über 140 Millionen Diabetiker, von denen etwa ein Drittel eine diabetische Retinopathie entwickelt. Die Prävalenz von DME liegt bei diesen Patienten zwischen 7 % und 14 %, was auf schätzungsweise 4-5 Millionen DME-Patienten in China hinweist.
- First-in-class bispecific fusion protein showing promising results in previous clinical trials
- Potential for extended dosing intervals (12-16 weeks) compared to current treatments (4-8 weeks)
- Large market opportunity with 4-5 million DME patients in China
- Favorable safety and tolerability profile demonstrated in previous studies
- Still in early Phase 2 trials, facing competition from established treatments
- Long development timeline before potential commercialization
- Will need to prove superior efficacy compared to current standard of care (Faricimab)
This randomized, double-masked, multi-center, active-controlled Phase 2 clinical study (NCT06908876) aims to evaluate the efficacy and safety of intravitreal injections of efdamrofusp alfa in DME patients. A total of 150 participants will be enrolled and randomized in a 1:1:1 ratio to the IBI302 4 mg group, the IBI302 8 mg group, and the Faricimab (anti-VEGF/ANG-2 bispecific antibody) 6 mg group. The primary endpoint is the change in best corrected visual acuity (BCVA) from baseline in the study eye at week 16.
DME has become the leading cause of vision impairment among the diabetic population in
DME development is primarily driven by microvascular damage mediated by VEGF upregulation and inflammatory factors2. Complement activation is also involved in the development of DME by damaging the neurovascular units through cytolysis, opsonization, and promotion of proinflammatory microenvironment, leading to retinal microvascular lesions, neurodegeneration, and macular edema3. At present, intravitreal injections of anti-VEGF agents or glucocorticoids are key treatment strategies, effectively improving visual acuity and retinal edema. However, frequent intravitreal injections (every 4 to 8 weeks) can result in poor patient compliance and increased risk of complications such as cataract and elevated intraocular pressure, making it challenging to achieve sustained visual acuity benefits with long-term treatment4,5. In recent years, bispecific antibodies represented by Faricimab have demonstrated significant efficacy and extended dosing intervals in patients with DME; Faricimab currently represents the highest global treatment standard for DME.
Efdamrofusp alfa, the first-in-class bispecific fusion protein targeting VEGF and complement, can simultaneously inhibit angiogenesis and vascular leakage mediated by VEGF, and inflammatory responses mediated by complement activation. To date, multiple clinical studies of efdamrofusp alfa have been conducted in patients with neovascular age-related macular degeneration (nAMD) and DME, among which high-dose (8 mg) efdamrofusp alfa has shown significant efficacy in improving visual acuity and retinal edema. Meanwhile, efdamrofusp alfa has demonstrated the potential for extended dosing intervals (up to 12-16 weeks), with favorable safety and tolerability.
Professor Xiaodong Sun, the leading Principal Investigator of this Study, Deputy Director of Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and Director of the Ophthalmology Center, stated, " DME is one of the most common ocular fundus diseases in
Dr. Lei Qian, Senior Vice President of Clinical Development of Innovent, stated, "Efdamrofusp alfa is an anti-VEGF-complement bispecific fusion protein self-developed by Innovent with global proprietary rights. This clinical study will be globally the first study comparing two dual-target agents, using Faricimab, the global standard of care in DME. We look forward to the success of this study, which could provide support for a Phase 3 clinical trial and a new treatment option for patients. Innovent's general biomedicine pipeline covers cardiovascular, endocrine and metabolic, ophthalmology, and autoimmune disease areas. We will continue to develop new therapies, providing physicians with more clinical treatment options and benefiting more patients."
About diabetic macular edema
Diabetic retinopathy (DR) is a series of lesions caused by retinal microvascular damage resulting from diabetes and is the main microvascular complication of diabetes. Diabetic macular edema (DME), featuring retinal edema, thickening and exudation, is caused by capillary leakage in the macular area. It is the result of the blood-retinal barrier (BRB) destruction and mainly affects central vision. At present, DR has become the leading cause of blindness among the working-age population worldwide, while DME has become the main cause of visual impairment among the diabetic population6.
The pathological mechanisms of DR and DME are multifactorial, involving metabolic abnormalities related to hyperglycemia, oxidative stress, and inflammation. These processes lead to the upregulation of vasoactive factors such as VEGF, which subsequently disrupt the BRB and increase vascular permeability, manifesting clinically as retinal edema and exudation. When the macular area is involved, it develops into DME2. Additionally, complement system activation contributes to disease progression by damaging the neurovascular units through cytolysis, opsonization, and promotion of proinflammatory microenvironment, causing retinal microvascular lesions, neurodegeneration, macular edema, and retinal neovascularization3.
About Effamrofusp Alfa (IBI302)
Efdamrofusp alfa is a recombinant, fully human bispecific fusion protein developed by Innovent Biologics with global intellectual property rights. The N-terminal is the VEGF-binding domain, which can bind to the VEGF family to block the VEGF-mediated signaling pathway, inhibiting the survival and proliferation of vascular endothelial cells, thereby inhibiting angiogenesis, reducing vascular permeability, and reducing vascular leakage. The C-terminal is the complement binding domain, which can inhibit complement activation through the classical pathway and the bypass pathway by specifically binding to C3b and C4b, and thereby alleviate the inflammatory response mediated by complement activation. Through this dual mechanism, efdamrofusp alfa exerts its therapeutic effects by inhibiting both VEGF-mediated angiogenesis and complement activation pathways.
About Innovent
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 15 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, 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.
Statement: Innovent does not recommend the use of any unapproved drugs/indications.
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References
1. 中华医学会眼科学分会眼底病学组, 中国医师协会眼科医师分会眼底病学组. 我国糖尿病视网膜病变临床诊疗指南（2022年）. 中华眼底病杂志. 2023;39(02):99-124.
2. Kusuhara S, Fukushima Y, Ogura S, Inoue N, Uemura A. Pathophysiology of Diabetic Retinopathy: The Old and the New. Diabetes Metab J. 2018;42(5):364-376.
3. Jiang F, Lei C, Chen Y, Zhou N, Zhang M. The complement system and diabetic retinopathy. Surv Ophthalmol. 2024;69(4):575-584.
4. Ehlken C, Ziemssen F, Eter N, et al. Systematic review: non-adherence and non-persistence in intravitreal treatment. Graefes Arch Clin Exp Ophthalmol. 2020;258(10):2077-2090.
5. Ciulla TA, Bracha P, Pollack J, Williams DF. Real-world Outcomes of Anti-Vascular Endothelial Growth Factor Therapy in Diabetic Macular Edema in
6. Tan GS, Cheung N, Simó R, et al. Diabetic macular oedema. Lancet Diabetes Endocrinol, 2017, 5(2): 143-155.
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FAQ
What is efdamrofusp alfa (IBI302) and how does it treat DME?
How many patients will be enrolled in IVBIY's Phase 2 trial for efdamrofusp alfa?
What advantages does efdamrofusp alfa offer over current DME treatments?
What is the market size for DME treatment in China?
What is the primary endpoint of IVBIY's Phase 2 trial for efdamrofusp alfa?
