Conbercept

Conbercept, sold under the commercial name Lumitin, is a novel vascular endothelial growth factor (VEGF) inhibitor used to treat neovascular age-related macular degeneration (AMD)[1][2] and diabetic macular edema (DME).[3] The anti-VEGF was approved for the treatment of neovascular AMD by the China State FDA (CFDA) in December 2013.[4][5] As of December 2020, conbercept is undergoing phase III clinical trials through the U.S. Food and Drug Administration’s PANDA-1 and PANDA-2 development programs.[6][7]

Conbercept
Clinical data
Trade namesLumitin
Routes of
administration		Intravitreal Injection
Identifiers
CAS Number
UNII
Chemical and physical data
Molar mass142 KDa

Conbercept was developed by Chengdu Kanghong Biotech Company in the People’s Republic of China and is marketed under the name Lumitin.[3][8]

Medical uses

It is used for the treatment of neovascular age-related macular degeneration (nAMD),[1][4][8] choroidal neovascularization secondary to pathologic myopia (pmCNV),[9][10] diabetic macular edema (DME).[3][11] The medication is given through intravitreal injection (IVT).[3][1]

Contraindications

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]
  • Conbercept provides significantly visual acuity improvement in DME patients (SAILING study).[28][29]

Society and culture
  • 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]

References
  1. Zhang J, Liang Y, Xie J, Li D, Hu Q, Li X, et al. (June 2018). "Conbercept for patients with age-related macular degeneration: a systematic review". BMC Ophthalmology. 18 (1): 142. doi:10.1186/s12886-018-0807-1. PMC 6003117. PMID 29902977.
  2. Lu X, Sun X (2015). "Profile of conbercept in the treatment of neovascular age-related macular degeneration". Drug Design, Development and Therapy. 9: 2311–20. doi:10.2147/DDDT.S67536. PMC 4410828. PMID 25960634.
  3. Cai S, Yang Q, Li X, Zhang Y (2018). "The efficacy and safety of aflibercept and conbercept in diabetic macular edema". Drug Design, Development and Therapy. 12: 3471–3483. doi:10.2147/DDDT.S177192. PMC 6197825. PMID 30410308.
  4. Wang L, Zhang C, Hua R (2018). "Clinical effectiveness of ranibizumab and conbercept for neovascular age-related macular degeneration: a meta-analysis". Drug Design, Development and Therapy. 12: 3625–3633. doi:10.2147/DDDT.S176021. PMC 6211581. PMID 30464394.
  5. Wang Y, Shen M, Cheng J, Sun X, Kaiser PK (2020). "The Efficacy of Conbercept in Polypoidal Choroidal Vasculopathy: A Systematic Review". Journal of Ophthalmology. 2020: 4924053. doi:10.1155/2020/4924053. PMC 7442996. PMID 32855818.
  6. Clinical 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
  7. 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
  8. de Oliveira Dias JR, de Andrade GC, Novais EA, Farah ME, Rodrigues EB (2016). "Fusion proteins for treatment of retinal diseases: aflibercept, ziv-aflibercept, and conbercept". International Journal of Retina and Vitreous. 2: 3. doi:10.1186/s40942-016-0026-y. PMC 5088480. PMID 27847621.
  9. Zhang Y, Han Q, Ru Y, Bo Q, Wei RH (2015). "Anti-VEGF treatment for myopic choroid neovascularization: from molecular characterization to update on clinical application". Drug Design, Development and Therapy. 9: 3413–21. doi:10.2147/DDDT.S87920. PMC 4494177. PMID 26170626.
  10. Yan M, Huang Z, Lian HY, Song YP, Chen X (August 2019). "Conbercept for treatment of choroidal neovascularization secondary to pathologic myopia". Acta Ophthalmologica. 97 (5): e813–e814. doi:10.1111/aos.13632. PMID 30187680. S2CID 52162973.
  11. Sun X, Zhang J, Tian J, Chen S, Zeng F, Yuan G (2020). "Comparison of the Efficacy and Safety of Intravitreal Conbercept with Intravitreal Ranibizumab for Treatment of Diabetic Macular Edema: A Meta-Analysis". Journal of Ophthalmology. 2020: 5809081. doi:10.1155/2020/5809081. PMC 7125465. PMID 32280526.
  12. "EU Clinical Trials Register". Clinical Trials Register.
  13. Li X, Xu G, Wang Y, Xu X, Liu X, Tang S, et al. (AURORA Study Group) (September 2014). "Safety and efficacy of conbercept in neovascular age-related macular degeneration: results from a 12-month randomized phase 2 study: AURORA study". Ophthalmology. 121 (9): 1740–7. doi:10.1016/j.ophtha.2014.03.026. PMID 24793528.
  14. Cui J, Sun D, Lu H, Dai R, Xing L, Dong H, et al. (February 2018). "Comparison of effectiveness and safety between conbercept and ranibizumab for treatment of neovascular age-related macular degeneration. A retrospective case-controlled non-inferiority multiple center study". Eye. 32 (2): 391–399. doi:10.1038/eye.2017.187. PMC 5805597. PMID 28937147. S2CID 44026758. (p. 397, Table 2)
  15. Stewart MW (January 2018). "Extended Duration Vascular Endothelial Growth Factor Inhibition in the Eye: Failures, Successes, and Future Possibilities". Pharmaceutics. 10 (1): 21. doi:10.3390/pharmaceutics10010021. PMC 5874834. PMID 29382038.
  16. Sacconi R, Giuffrè C, Corbelli E, Borrelli E, Querques G, Bandello F (2019-08-12). "Emerging therapies in the management of macular edema: a review". F1000Research. 8: 1413. doi:10.12688/f1000research.19198.1. PMC 6694451. PMID 31448093.
  17. Cui C, Lu H (2018). "Clinical observations on the use of new anti-VEGF drug, conbercept, in age-related macular degeneration therapy: a meta-analysis". Clinical Interventions in Aging. 13: 51–62. doi:10.2147/CIA.S151225. PMC 5747960. PMID 29343949.
  18. "China Focus: Innovation boosts development of China's private medical companies". www.xinhuanet.com. Archived from the original on 2018-12-17. Retrieved 2021-02-05.
  19. "International Nonproprietary Names for Pharmaceutical Substances (INN)" (PDF). World Health Organization. 2012.
  20. "China Focus: Innovation boosts development of China's private medical companies". www.xinhuanet.com. Archived from the original on 2018-12-17. Retrieved 2021-02-24.
  21. "The Phase 3 Clinical Trial of Conbercept for Exudative AMD". Retinal Physician. Retrieved 2021-02-05.
  22. Ferro Desideri L, Traverso CE, Nicolò M (May 2020). "An update on conbercept to treat wet age-related macular degeneration". Drugs of Today. 56 (5): 311–320. doi:10.1358/dot.2020.56.5.3137164. PMID 32406878.
  23. Clinical trial number NCT03108352 for "Conbercept Ophthalmic Injection for Patients With Macular Edema Caused by Branch Retinal Vein Occlusion (BRAVE)" at ClinicalTrials.gov
  24. "创新赋能 责任担当 康弘药业高成长性再获认可 | 每经网". www.nbd.com.cn. Retrieved 2021-03-15.
  25. "走进"一带一路"，中国创新药康柏西普在蒙古国获批上市--人民健康网--人民网". health.people.com.cn. Retrieved 2021-03-15.
  26. Liu, Kun; Song, Yanping; Xu, Gezhi; Ye, Jian; Wu, Zhifeng; Liu, Xiaoling; Dong, Xiaoguang; Zhang, Mingzhi; Xing, Yiqiao; Zhu, Shaoping; Chen, Xia (August 2018). "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. PMID 30148987.
  27. 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. PMID 26595362. S2CID 23512450.
  28. Wang H, Guo J, Tao S, Wang X, Liu X, Li T, et al. (May 2020). "One-Year Effectiveness Study of Intravitreously Administered Conbercept® Monotherapy in Diabetic Macular Degeneration: A Systematic Review and Meta-Analysis". Diabetes Therapy. 11 (5): 1103–1117. doi:10.1007/s13300-020-00806-0. PMC 7192996. PMID 32236812.
  29. Clinical trial number NCT02194634 for "Safety and Efficacy Study of Conbercept in Diabetic Macular Edema (DME) (Sailing)" at ClinicalTrials.gov
  30. "The Phase 3 Clinical Trial of Conbercept for Exudative AMD". www.retinalphysician.com. Retrieved 2021-02-17.
  31. "In-depth company research, Kanghong Pharmaceutical" (PDF).
  32. Chen R, Wu B (August 2020). "Cost-effectiveness of intravitreal conbercept versus other treatments for wet age-related macular degeneration". Annals of Translational Medicine. 8 (15): 939. doi:10.21037/atm-20-1334. PMC 7475432. PMID 32953739.
  33. Gao L, Liu J, Zhang P, Ma J, Wang H (May 2020). "Clinical outcomes of 1 + PRN and 3 + Q3M regimens of intravitreal conbercept injection for exudative age-related macular degeneration". Scientific Reports. 10 (1): 8010. Bibcode:2020NatSR..10.8010G. doi:10.1038/s41598-020-65000-5. PMC 7224199. PMID 32409739.
  • Conbercept, Drug Information Portal. U.S. National Library of Medicine.
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