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Conbercept

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

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 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

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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

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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

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Common adverse effects of the eye formulation include eye pain, transient intraocular pressure (IOP) increase and conjunctival hemorrhage.[13][14]

Mechanism of action

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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

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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

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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

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  • 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

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[edit]
  • 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

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  • 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

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  1. ^ a b c d 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. ^ a b c d 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. ^ a b c d 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. ^ a b c 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. ^ a b 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. S2CID 218632826.
  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 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. PMID 30148987. S2CID 52100991.
  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. ^ a b 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).[permanent dead link]
  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.
[edit]
  • Conbercept, Drug Information Portal. U.S. National Library of Medicine.
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