Delving into the Latest Updates on Eflimrufusp alfa with Synapse

Overview

Basic Info

Drug Type

Antibody fusion proteins

Synonyms

Target

VEGF x bFGF

Mechanism

VEGF inhibitors(Vascular endothelial growth factor inhibitors), bFGF inhibitors(Fibroblast growth factor 2 inhibitors)

Therapeutic Areas

Cardiovascular DiseasesCongenital DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Diabetic macular oedemaWet age-related macular degenerationNonproliferative diabetic retinopathy

Inactive Indication-

Originator Organization

RemeGen Co., Ltd.

Active Organization

RemeGen Co., Ltd.

Inactive Organization-

Drug Highest PhasePhase 3

First Approval Date-

RegulationSpecial Review Project (CN)

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Gene Sequence

Sequence Code 524756270

Source: *****

INTRODUCTIONTo assess the safety and efficacy of repeated intravitreal injections of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with neovascular age-related macular degeneration (AMD). This was a prospective, multicenter, open-label clinical trial; 37 patients with choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) letter scores between 73 and 34 were enrolled.METHODSTreatment regimens consisted of a 3-month loading phase and a pro re nata (PRN) maintenance phase. This study included three treatment groups: the 0.5, 1.0, and 2.0 mg RC28-E groups, with escalating doses ranging from 0.5 to 2.0 mg. Patients were evaluated monthly for 48 weeks. Safety was assessed based on ocular and systemic adverse events (AEs), pharmacokinetic characteristics, and the presence of anti-RC28-E antibodies. Efficacy was assessed using the mean change in BCVA and central subfield thickness (CST) from baseline to week 48.RESULTSMost AEs were mild or moderate. The most common AE was a minor injection-related subconjunctival hemorrhage (16.2%). The AEs did not increase with dose or repeated injections. At week 48, mean improvements in BCVA from baseline in the 0.5, 1.0, and 2.0 mg groups were 6.1 ± 8.3, 9.9 ± 10.7, and 7.6 ± 9.38 letters, respectively; mean reductions in CST in the three groups were 112.1 ± 160.5, 175.1 ± 212.4, and 128.7 ± 145.8 μm, respectively. The serum RC28-E concentrations in 95% of the patients were below the quantification limit of the assay. No significant change from baseline was observed in the mean plasma concentrations of VEGF or FGF over the 48 weeks of treatment. Pre-treatment antibodies to RC28-E were detected in 1 of the 37 patients. Antibodies to RC28-E were detected in two patients after dosing with RC28-E for 48 weeks.CONCLUSIONRC28-E was well tolerated and exhibited an overall favorable safety profile with evidence of improvements in BCVA and anatomical parameters.

01 Jan 2020·Experimental Eye ResearchQ3 · MEDICINE

In vivo characterization of RC28-E, a fusion protein targeting VEGF and bFGF: Pharmacokinetics and ocular distribution in primates

Q3 · MEDICINE

Article

Author: Wu, Chuandong ; Kou, Xiangying ; Huang, Min ; Wang, Ling ; Liu, Zhihao ; Jiang, Jing ; Li, Hongzhen

Administration of RC28-E, a VEGF/bFGF dual decoy receptor (IgG1 Fc-fusion protein), have shown relative therapeutic value in ocular in vivo models, including laser-induced choroidal neovascularization (CNV) in monkeys and streptozotocin (STZ)-induced diabetic retinopathy (DR) in rats. In the present study, we have elucidated the pharmacokinetics profiles of RC28-E at the systemic, vitreous and aqueous humor after administration in a primate model (Macaca fascicularis). Moreover, here we tease out the ocular tissue distribution of RC28-E after intravitreal administration, and we also determine the systemic bioavailability after both intravitreal and intravenous administration. Our results show that RC28-E is rapidly and well-distributed into ocular tissues after intravitreal administration. Drug exposure in choroid and retina was approximately one-quarter and one-twelfth of that in vitreous humor, while its half-life in vitreous and aqueous humor were well-sustained (3.3 and 3.0 days). Remarkably, RC28-E could cross the blood-ocular barrier, and the systemic bioavailability of RC28-E was ~25%. No drug accumulation after multiple administration was noticed, but low titers of antibody produce against RC28-E were detected. Overall, RC28-E exhibited high clinical value due to adequate pharmacokinetic profiling, safety and efficacy.

01 Aug 2018·European Journal of Pharmaceutical SciencesQ2 · MEDICINE

Pharmacology study of a chimeric decoy receptor trap fusion protein on retina neovascularization by dual blockage of VEGF and FGF-2

Q2 · MEDICINE

Article

Author: Fang, Jianmin ; Wang, Ling ; Xu, Ke ; Xin, Wei ; Zhao, Guorui ; Jiang, Jing ; Luan, Xuejing ; Huang, Min ; Li, Shenjun

BACKGROUNDClinical anti-vascular epithelial growth factor (VEGF) therapy trials faced a major challenge due to upregulated expression of other pro-angiogenic factors, such as fibroblast growth factor-2 (FGF-2). RC28, a novel recombinant dual decoy receptor IgG1 Fc-fusion protein, can block VEGFA and FGF-2 simultaneously. It is designed for the treatment of neovascular age-related macular degeneration and other pathological ocular neovascularization. The present study investigated the prevention efficacy of RC28 on choroidal neovascularization (CNV) in a monkey model and compared to the other mono VEGF antagonists; biodistribution and pharmacokinetics performance were also investigated.METHODSELISA and endothelial cell proliferation, migration, and tubule formation assay evaluated the bioactivity of RC28 in vitro, and an initial comparison was made among the mono target antagonists, Bevacizumab (Avastin), Ranibizumab (Lucentis), Aflibercept (EYLEA), Conbercept (KH902), and Ranibizumab (Lucentis). Laser-induced CNV in monkeys, and both VEGF and FGF-2 serum levels were detected in animals before and after the CNV model were induced. RC28 prevention efficacy was compared to other VEGF antagonists on CNV with respect to the incidence of CNV and several ophthalmic examinations. Ocular and systemic levels of RC28 were analyzed by ⁸⁹Zr-labeled RC28 after single intravitreal administration for the biodistribution and pharmacokinetic profiles.RESULTSRC28 is a unique fusion protein with high affinity to both VEGF and FGF-2, and beneficial to in vitro and in vivo bioactivity. The in vivo pharmacological studies demonstrated that the incidence of CNV formation was largely reduced in RC28 treatment groups with a low dosage as compared to other VEGF antagonist control groups. Furthermore, traces of RC28 were detected as dispersing from eyeballs to the liver after 20 days, and a prolonged half-time pharmacokinetic profile was exhibited.

100 Deals associated with Eflimrufusp alfa

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetic macular oedema	Phase 3	CN	RemeGen Co., Ltd.	08 Jun 2023
Wet age-related macular degeneration	Phase 3	CN	RemeGen Co., Ltd.	14 Mar 2023
Nonproliferative diabetic retinopathy	Phase 2	CN	RemeGen Co., Ltd.	25 May 2021

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04270669 \| CTR20192638 (NEWS) Manual	Phase 1	Wet age-related macular degeneration	-	RC28-E	(dvpeegcjht) = Patients using Rongchang BioRC28 demonstrated good tolerability and safety, with significant improvements in vision and disease, and were effective in patients who had previously received anti-VEGF therapy and PCV (fundus polypoid choroidal vasculopathy). zwwdvwvsct (nfnjmyebwh )	Positive	15 Sep 2022
ARVO2012	Not Applicable	-	-	RC28	(auxxchvsud) = ajvjkenwqs bkslmklwto (izblanqbbh ) View more	-	01 Mar 2012