CASE STUDY3: INFLIXIMAB & ITS BIOSIMILAR
Infliximab is a chimeric, anti-tumor necrosis factor monoclonal antibody which is effective in patients with active rheumatoid arthritis. Infliximab is traded under the name “remicade” and is originally licensed by Janssen. It works by binding to TNF-α and inhibits the binding of TNF-α with its receptor. TNF-α is a cytokine (chemical messenger) that is involved in systemic inflammation. CT-P13 (brand name- inflectra) is a biosimilar of infliximab approved by FDA in 2016.
A Phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54 week results from the PLANETRA study
Dae Hyun Yoo et al conducted a study to compare the safety and efficacy of CT-P13 (biosimilar) with the reference infliximab (remicad) [8]. To assess this equivalence, a PLANETRA study was conducted, i.e, Programme evaLuating the Auto immune disease iNvEstigational drug cT-p13 in RA patients. Patients were randomly given ct-p13 and reference product upto 54 weeks along with methotrexate which is a immune system suppressant. Then after 54 weeks, safety and efficacy of both the drugs were compared on the basis of ACR response rates, disease activity score in 28 joints (DAS28), etc. Also the immunogenicity, safety, PK & PD parameters were assessed. ACR response rates:- ACR criteria stands for American College for Rheumatology criteria, developed n 1980. The criteria consists of clinical symptoms and signs of inflammation that include joint pain, joint swelling, morning stiffness, erythrocyte sedimentation rate, etc. FINDINGS:- • Comparable ACR response rates as shown in graph8. ACR criteria RP CT-P13 ACR20 71.3% 74.7% ACR50 43.1% 43.6% ACR70 19.9% 21.3% • Similar changes is DAS28 as shown in graph9. • The proportion of patients positive for antidrug antibodies at week 54 was similar between the two groups. • Similar safety profiles • Comparable PK/PD results. …show more content…
Graph8: ACR response curve for both groups Graph9: DAS28 response curves for both groups
CASE STUDY 4: RITUXIMAB & ITS BIOSIMILAR
Rituximab is monoclonal antibody used to reduce auto-immune disorders, transplant rejections, etc. Rituximab binds to CD20 proteins which are found on the surface of B cells and decrease the effectiveness of natural killer cells in killing these B cells. It destroys B cells and hence treat dysfunctional or excessive number of B cells. Rituximab was developed at IDEC Pharmaceuticals and its patent got expired in 2015.
“Physicochemical and functional comparability between the proposed biosimilar Rituximab GP2013 and originator Rituximab”
Jan Visser et al conducted a study to demonstrate the similarity among the originator rituximab and GP2013 [9].
Methods Involved: 1) Functional Bioassay 2)Cation exchange chromatography 3)Glycan analysis
Functional bioassays:- Using a cell based competitive binding assay, binding of rituximab to CD20 is determined. In this, test samples are used to displace fluorescently labelled rituximab from CD20. This helps to quantify Fc effector functions and ADCC activity. Cation- exchange chromatography:- It is a form of ion exchange chromatography which is used to separate molecules on the basis of net surface charge. It is used when molecules to be separated are cations. Glycan Analysis:- It is a highly sensitive method for quantitatively and qualitatively analysing glycans in monoclonal antibodies. The method involves separating the glycans using gel filtration chromatography and then the sample is analysed under fluorescent detectors. FINDINGS: • GP013 was found to be comparable with original rituximab in CDC and ADCC activity. • The
Infliximab is a chimeric, anti-tumor necrosis factor monoclonal antibody which is effective in patients with active rheumatoid arthritis. Infliximab is traded under the name “remicade” and is originally licensed by Janssen. It works by binding to TNF-α and inhibits the binding of TNF-α with its receptor. TNF-α is a cytokine (chemical messenger) that is involved in systemic inflammation. CT-P13 (brand name- inflectra) is a biosimilar of infliximab approved by FDA in 2016.
A Phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54 week results from the PLANETRA study
Dae Hyun Yoo et al conducted a study to compare the safety and efficacy of CT-P13 (biosimilar) with the reference infliximab (remicad) [8]. To assess this equivalence, a PLANETRA study was conducted, i.e, Programme evaLuating the Auto immune disease iNvEstigational drug cT-p13 in RA patients. Patients were randomly given ct-p13 and reference product upto 54 weeks along with methotrexate which is a immune system suppressant. Then after 54 weeks, safety and efficacy of both the drugs were compared on the basis of ACR response rates, disease activity score in 28 joints (DAS28), etc. Also the immunogenicity, safety, PK & PD parameters were assessed. ACR response rates:- ACR criteria stands for American College for Rheumatology criteria, developed n 1980. The criteria consists of clinical symptoms and signs of inflammation that include joint pain, joint swelling, morning stiffness, erythrocyte sedimentation rate, etc. FINDINGS:- • Comparable ACR response rates as shown in graph8. ACR criteria RP CT-P13 ACR20 71.3% 74.7% ACR50 43.1% 43.6% ACR70 19.9% 21.3% • Similar changes is DAS28 as shown in graph9. • The proportion of patients positive for antidrug antibodies at week 54 was similar between the two groups. • Similar safety profiles • Comparable PK/PD results. …show more content…
Graph8: ACR response curve for both groups Graph9: DAS28 response curves for both groups
CASE STUDY 4: RITUXIMAB & ITS BIOSIMILAR
Rituximab is monoclonal antibody used to reduce auto-immune disorders, transplant rejections, etc. Rituximab binds to CD20 proteins which are found on the surface of B cells and decrease the effectiveness of natural killer cells in killing these B cells. It destroys B cells and hence treat dysfunctional or excessive number of B cells. Rituximab was developed at IDEC Pharmaceuticals and its patent got expired in 2015.
“Physicochemical and functional comparability between the proposed biosimilar Rituximab GP2013 and originator Rituximab”
Jan Visser et al conducted a study to demonstrate the similarity among the originator rituximab and GP2013 [9].
Methods Involved: 1) Functional Bioassay 2)Cation exchange chromatography 3)Glycan analysis
Functional bioassays:- Using a cell based competitive binding assay, binding of rituximab to CD20 is determined. In this, test samples are used to displace fluorescently labelled rituximab from CD20. This helps to quantify Fc effector functions and ADCC activity. Cation- exchange chromatography:- It is a form of ion exchange chromatography which is used to separate molecules on the basis of net surface charge. It is used when molecules to be separated are cations. Glycan Analysis:- It is a highly sensitive method for quantitatively and qualitatively analysing glycans in monoclonal antibodies. The method involves separating the glycans using gel filtration chromatography and then the sample is analysed under fluorescent detectors. FINDINGS: • GP013 was found to be comparable with original rituximab in CDC and ADCC activity. • The