Conbercept is contraindicated in patients with known hypersensitivity to the active ingredient,[6] in patients with ocular or periocular infections,[12] and in patients with active intraocular inflammation.[6]
Adverse effects
Common adverse effects of the eye formulation include eye pain, transient
intraocular pressure (IOP) increase and conjunctival hemorrhage.[13][14]
Mechanism of action
Conbercept is a soluble receptor decoy that binds specifically to
VEGF-B,
placental growth factor (PlGF), and various
isoforms of
VEGF-A.[1][4][15] Conbercept has a VEGF-R2
kinase insert domain receptor (KDR) Ig-like region 4 (KDRd4) which improves the three-dimensional structure and efficiency of dimer formation, thereby increasing the binding capacity of conbercept to VEGF.[16]
Composition
Conbercept is a
recombinant fusion protein composed of VEGFR-1 (second domain) and VEGFR-2 (third and fourth domains) regions fused to the Fc portion of human IgG1 immunoglobulin.[4][17]
History
Chengdu Kanghong Pharmaceutical Group, a medical company based in
Sichuan, started the development of conbercept in 2005.[18] In 2012, the drug was included on the
World Health Organization’s Drug Information 67th List of Recommended International Nonproprietary Names,[19] which was the first Chinese innovator biotech drug to be recognized on the list.[20]
In November 2013, the Chinese Food and Drug Administration approved conbercept for the treatment of AMD.[21] By 2014, conbercept was marketed for treatment of wAMD in China.[22] In 2016, Phase III clinical trials of conbercept were authorized by the U.S. Food and Drug Administration.[23]
In 2017, Kanghong Pharmaceutical Group partnered with
Syneos Health to process Phase III clinical trials simultaneously in more than 30 countries around the world with an investment of $228 million.[24] In 2020, conbercept was approved for use in
Mongolia.[25]
Clinical trials in China
Conbercept is the only anti-VEGF drug confirmed by randomized controlled trials (RCT) to sustain visual improvements with 3+Q3M regimens (PHOENIX study)[26]
Conbercept significantly improves visual acuity and anatomical outcomes in patient with
PCV (AURORA Study).[27]
In 2013, the CFDA approved conbercept for the treatment of neovascular age-related macular degeneration (nAMD)[30]
In 2017, the CFDA approved it for the treatment of pathologic myopia associated choroidal neovascularization (pmCNV) [31]
In 2019, the CFDA approved it for the treatment of diabetic macular edema (DME)[28]
Economic
Conbercept has been shown to be a cost-effective wAMD treatment option in China. Compared to two similar anti-VEGF intravitreal drugs,
ranibizumab and
aflibercept, conbercept has been shown to be the most cost-effective option for treatment of wAMD in China.[32]
In 2017, the national basic medical insurance in China began covering conbercept.[33]
^
abcClinical trial number NCT03577899 for "A Multicenter, Double-Masked, Randomized, Dose-Ranging Trial to Evaluate the Efficacy and Safety of Conbercept Intravitreal Injection in Subjects With Neovascular Age-Related Macular Degeneration (AMD) (PANDA-1)" at
ClinicalTrials.gov
^Clinical trial number NCT03630952 for "A Multicenter, Double-Masked, Randomized, Dose-Ranging Trial to Evaluate the Efficacy and Safety of Conbercept Intravitreal Injection in Subjects With Neovascular Age-Related Macular Degeneration (AMD) (PANDA-2)" at
ClinicalTrials.gov
^Clinical trial number NCT03108352 for "Conbercept Ophthalmic Injection for Patients With Macular Edema Caused by Branch Retinal Vein Occlusion (BRAVE)" at
ClinicalTrials.gov
^Liu K, Song Y, Xu G, Ye J, Wu Z, Liu X, et al. (January 2019). "Conbercept for Treatment of Neovascular Age-related Macular Degeneration: Results of the Randomized Phase 3 PHOENIX Study". American Journal of Ophthalmology. 197: 156–167.
doi:
10.1016/j.ajo.2018.08.026.
PMID30148987.
S2CID52100991.
^Qu J, Cheng Y, Li X, Yu L, Ke X (May 2016). "EFFICACY OF INTRAVITREAL INJECTION OF CONBERCEPT IN POLYPOIDAL CHOROIDAL VASCULOPATHY: Subgroup Analysis of the Aurora Study". Retina. 36 (5): 926–37.
doi:
10.1097/IAE.0000000000000875.
PMID26595362.
S2CID23512450.