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ACG Public Forum

Monday, 12:45 pm 2:15 pm

Biosimilars for IBD: What the Gastroenterologist Needs

to Know

Tara Altepeter, MDClinical Team Leader

Division of Gastroenterology and Inborn Errors ProductsUS Food and Drug Administration

10/16/2017

2

Disclosures The views expressed in this presentation are my

own and are not intended to convey official FDA policy.

I have no financial conflicts of interest to disclose.

The product specific details presented are used to exemplify the principles being discussed. All of this information is available in the public domain, and is not intended to promote any particular product.

3

What Questions Do Clinicians Have? What does biosimilarity mean to a clinician?

How is this different from a generic drug? Why was the biosimilar product not studied in IBD?

What evidence is there that it will work for my patient? Should I be concerned about immunogenicity that may

occur with switching products? Do I have a choice in prescribing a biosimilar or not?

What about an interchangeable product?

4


How is this different from a generic drug? Why was the biosimilar product was never studied in IBD?

What evidence is there that it will work for my patient? What is known about immunogenicity that may occur with

switching products? Do I have a choice in prescribing a biosimilar or not?

What about an interchangeable product? Case study

5

Biosimilarity: Definition

Biosimilar or Biosimilarity means: that the biological product is highly similar to the

reference product notwithstanding minor differences in clinically inactive components; and

there are no clinically meaningful differencesbetween the biological product and the reference product in terms of the safety, purity, and potency of the product

5

6

Framework to consider what Biosimilar means

8



What evidence is there that it will work for my patient? What is known about immunogenicity that may occur with

switching products? Do I have a choice in prescribing a biosimilar or not?


9

Stepwise Approach to Demonstrating Similarity

10

Extrapolation The potential exists for a biosimilar product to be approved

for one or more conditions of use for which the US-licensed reference product is licensed based on extrapolation of clinical data intended to demonstrate biosimilarity in one condition of use

Sufficient scientific justification for extrapolating data is necessary

11

Scientific Justification Mechanism of Action (MOA) if known, in each condition

of use for which licensure is sought PK and bio-distribution of the product in different patient

populations Immunogenicity of the product in different patient

populations Differences in expected toxicities in each condition of use

and patient population Any other factor that may affect the safety or efficacy of

the product in each condition of use and patient population

12

Extrapolation Example Inflectra (infliximab-dyyb) developed as CT-P13 (Celltrion) First biosimilar to a TNF blocker approved by FDA Application included controlled clinical studies in Rheumatoid

Arthritis (RA) and Ankylosing Spondylitis (AS)

Did receive all the (eligible) indications as the US-licensed reference product (Remicade). Psoriatric Arthritis Plaque Psoriasis Adult and Pediatric Crohns Disease Adult Ulcerative Colitis*

1313

Known and Potential MOA of Infliximab

* Modest shift in mean activity of CT-P13 vs. reference product, within the established quality range

MOA of infliximab RA AS PsA PsO CDPediatric CD

UCPediatric UC

Similarity Criteria

Met

Blocking TNFR1 and TNFR2 activity via binding and neutralization of s/tmTNFYes Yes Yes Yes Likely Likely

Reverse (outside-to-inside) signaling via tmTNF:

Apoptosis of lamina propria activated T cells - - - - Likely Likely

Suppression of cytokine secretion - - - - Likely Likely

Mechanisms involving the Fc region of the antibody:

Induction of CDC on tmTNF-expressing target cells (via C1q binding)

- - - - Plausible Plausible

Induction of ADCC on tmTNF-expressing target cells (via FcRIIIa binding expressed on effector cells)

- - - - Plausible Plausible *

Induction of regulatory M in mucosal healing

- - - - Plausible Plausible

Adapted from Arthritis Advisory Committee, February 09, 2016

14

PK / Biodistribution PK is known to be similar across various patient

populations* For this reason, since the applicant demonstrated

PK similarity between CT-P13 and EU approved Remicade in multiple usage scenarios, the Agency accepted the rationale that PK differences would not be expected in the IBD population.

*as described in the reference product labelling

15

Immunogenicity Immunogenicity is primarily affected by the use

of concomitant medications across different indications, rather than patient populations.

As a result, meeting similarity criteria for immunogenicity in a sensitive population (with concomitant methotrexate in RA patients, and as monotherapy in AS patients) was felt to be sufficient extrapolate that immunogenicity is not expected to be different in IBD patients.

16

Toxicity Across multiple indications, the common and rare

but serious adverse events are noted to be similar. Major toxicities such as serious infections and

malignancies are similar across disease populations.

As a result, there was no reason to expect a different safety profile in IBD patients treated with CT-P13, compared to the reference product

17

Extrapolation Summary In summary, the applicant addressed the

mechanism(s) of action, PK, Immunogenicity and Safety across multiple indications

The Agency determined that the scientific justification was sufficient to extrapolate the approval of the Biosimilar to all of the eligible indications held by the reference product.

18



What evidence is there that it will work for my patient? What about immunogenicity that may occur with switching

products? Do I have a choice in prescribing a biosimilar or not?


19

Impact of Immunogenicity

19

20

Interchangeability: DefinitionInterchangeable or Interchangeability means:

The biological product is biosimilar to the reference product; It can be expected to produce the same clinical result as

the reference product in any given patient; and For a product that is administered more than once to an

individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the product and its reference product is not greater than the risk of using the reference product without such alternation or switch

Note: The interchangeable product may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product

20

21

Conclusions A biosimilar is highly similar to the reference product, and has no

clinically meaningful differences from the reference product. Biosimilars are evaluated very stringently to ensure that they are

highly similar. Despite not necessarily being studied in IBD, GI providers should feel

confident that the biosimilar has met a strict bar for similarity, and IBD indications were granted because there is no scientific basis to expect differences in clinical outcomes for IBD patients, compared to the reference product based on totality of the evidence, where clinical studies are a small piece of the overall data package.

Currently FDA has not approved any biosimilar as interchangeable.

22

Resources: FDA Guidance on Biosimilars:

https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM537135.pdf

FDA Draft Guidance on Interchangeability: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryI

nformation/Guidances/UCM537135.pdf

FDA Information of Biosimilars: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsare

DevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/default.htm

23

Additional Slides

24

QR Analysis: PBMC ADCC

ADCC assay uses Transfected transmembrane TNF- Jurkat cells as target cells PBMC from healthy donor as effector cells

24

405060708090

100110120130140150160170180

0 5 10 15 20 25 30 35

ADCC

PBM

C Re

lativ

e Po

tenc

y (%

)

US Licensed Remicade CT-P13 EU Licensed Remicade

Chart1

989792

101105106

93111104

105116108

111104126

123108102

11192107

8892103

11199107

121106108

US Licensed Remicade

CT-P13

EU Licensed Remicade

ADCC PBMC Relative Potency (%)

Data edit

(1)- US Remicade98

(1)- US Remicade101

(1)- US Remicade93

(1)- US Remicade105

(1)- US Remicade111

(1)- US Remicade123

(1)- US Remicade111

(1)- US Remicade88

(1)- US Remicade111

(1)- US Remicade121

(2)- CT-P1397

(2)- CT-P13105

(2)- CT-P13111

(2)- CT-P13116

(2)- CT-P13104

(2)- CT-P13108

(2)- CT-P1392

(2)- CT-P1392

(2)- CT-P1399

(2)- CT-P13106

(3)- EU Remicade92

(3)- EU Remicade106

(3)- EU Remicade104

(3)- EU Remicade108

(3)- EU Remicade126

(3)- EU Remicade102

(3)- EU Remicade107

(3)- EU Remicade103

(3)- EU Remicade107

(3)- EU Remicade108

Data

SourceADCC PMBC Relative Potency (%)US Licensed RemicadeCT-P13EU Licensed Remicade

(1)- US Remicade9899819972992

(1)- US Remicade10191011910529106

(1)- US Remicade939931911129104

(1)- US Remicade1059.510519.511630.5108

(1)- US Remicade1119.511119.510430126

(1)- US Remicade1239.512319.510830.5102

(1)- US Remicade1119.5111209230107

(1)- US Remicade8810.588209230103

(1)- US Remicade11110.511120.59929.5107

(1)- US Remicade1211012120.510629108

(2)- CT-P1397

(2)- CT-P13105

(2)- CT-P13111

(2)- CT-P13116

(2)- CT-P13104

(2)- CT-P13108

(2)- CT-P1392

(2)- CT-P1392

(2)- CT-P1399

(2)- CT-P13106

(3)- EU Remicade92

(3)- EU Remicade106

(3)- EU Remicade104

(3)- EU Remicade108

(3)- EU Remicade126

(3)- EU Remicade102

(3)- EU Remicade107

(3)- EU Remicade103

(3)- EU Remicade107

(3)- EU Remicade108

Data


CT-P13


ADCC PBMC Relative Potency (%)

Stats

ProductStats

US RemicadeMean106

SD11.4

+3SD-

-3SD-

CTP-13Mean103

SD7.9

+3SD140.43

-3SD71.97

EU RemicadeMean106

SD8.4

+3SD140.43

-3SD71.97

25

QR Analysis: NK-ADCC Cytotoxicity

NK-ADCC assay: Transfected transmembrane TNF- Jurkat cells used as target cells NK cells purified from peripheral blood used as effector cells

25

92% of CT-P13 Samples are within QR

2 ng/ml

4 ng/ml

8 ng/ml

Chart1

28.622.126.4

2826.623.7

29.923.625.3

26.122.525.7

26.621.227.9

24.723.925.9

24.420.823.8

2423.218.6

20.316.819.1

18.320.122.7

19.916.929.5

18.614.729.1

2017.424.2

24.726.530.6

32.42431.6

25.224.421.9

28.626.422.6

24.926.722.9

25.127.522.1

27.127.721.7

25.425.431.2

25.42628.4

24.426.530.2

25.722.125.7

23.314.322.3

27.120.323.9

25.628.528.1

28.733.129.1

26.332.928

32.326.328.7

32.431.533.9

30.728.536.9

31.829.934.8

27.935.342.7

23.928.840.5

43.13035.6

36.931.536.1

38.53136.9

3329.834.3

34.13443

37.932.635.4

38.831.239

36.231.341.9

37.233.442.1

40.23238.8

35.33522.7

33.835.730.2

38.530.527

41.930.427.5

36.824.631.7

32.528.436.7

34.424.537.8

28.734.635

37.242.135.2

35.437.633.7

37.834.930.9

28.23737

30.738.934.6

33.834.633.7

38.739.333.3

30.436.848.3

36.436.842

37.836.245.7

31.733.346.6

37.241.347.3

38.842.846.2

36.536.445

34.936.150.7

3351.245.9

33.149.348.5

48.853.942.1

44.352.759.3

47.449.768.9

43.55148.1

46.848.549.8

49.345.832.3

46.930.538.9

44.928.335.6

39.635

41.545.3

4748.6

44.939.9

50.745.6

57.938.4

59.138

53.236

4544.9

44.842

43.947.4

46.446.8

55

44.5

43.5

46.4

55.3

38.5

44.1

47

47.2

41.3

47.5

44.1

49.3

44.1

36.7


CT-P13


Absolute Cytotoxicity (%)

ADCC Cytotox (2)

ManufacturerCytotoxity (%)EU Remicade

(5) US-Remicade (8 ng/mL)48.82RMA6010348.333.926.4

(5) US-Remicade (8 ng/mL)44.31RMA649014236.923.7


(5) US-Remicade (8 ng/mL)43.53RMKA8070246.642.725.7



(5) US-Remicade (8 ng/mL)46.91RMKA871034536.123.8




(5) US-Remicade (8 ng/mL)474RMA6930442.135.429.5






(5) US-Remicade (8 ng/mL)454RMA7330438.930.222.6




(5) US-Remicade (8 ng/mL)555RMKA8060148.636.731.2







(5) US-Remicade (8 ng/mL)475RMA611044234.629.1



(5) US-Remicade (8 ng/mL)47.5





(6) CT-P13 (8 ng/ml)34.6

(6) CT-P13 (8 ng/ml)42.1

(6) CT-P13 (8 ng/ml)37.6

(6) CT-P13 (8 ng/ml)34.9

(6) CT-P13 (8 ng/ml)37

(6) CT-P13 (8 ng/ml)38.9

(6) CT-P13 (8 ng/ml)34.6

(6) CT-P13 (8 ng/ml)39.3

(6) CT-P13 (8 ng/ml)36.8

(6) CT-P13 (8 ng/ml)36.8

(6) CT-P13 (8 ng/ml)36.2

(6) CT-P13 (8 ng/ml)33.3

(6) CT-P13 (8 ng/ml)41.3

(6) CT-P13 (8 ng/ml)42.8

(6) CT-P13 (8 ng/ml)36.4

(6) CT-P13 (8 ng/ml)36.1

(6) CT-P13 (8 ng/ml)51.2

(6) CT-P13 (8 ng/ml)49.3

(6) CT-P13 (8 ng/ml)53.9

(6) CT-P13 (8 ng/ml)52.7

(6) CT-P13 (8 ng/ml)49.7

(6) CT-P13 (8 ng/ml)51

(6) CT-P13 (8 ng/ml)48.5

(6) CT-P13 (8 ng/ml)45.8

(6) CT-P13 (8 ng/ml)30.5

(6) CT-P13 (8 ng/ml)28.3




(3) US-Remicade (4 ng/mL)33
































(4) CT-P13 (4 ng/ml)28.5

(4) CT-P13 (4 ng/ml)33.1

(4) CT-P13 (4 ng/ml)32.9

(4) CT-P13 (4 ng/ml)26.3

(4) CT-P13 (4 ng/ml)31.5

(4) CT-P13 (4 ng/ml)28.5

(4) CT-P13 (4 ng/ml)29.9

(4) CT-P13 (4 ng/ml)35.3

(4) CT-P13 (4 ng/ml)28.8

(4) CT-P13 (4 ng/ml)30

(4) CT-P13 (4 ng/ml)31.5

(4) CT-P13 (4 ng/ml)31

(4) CT-P13 (4 ng/ml)29.8

(4) CT-P13 (4 ng/ml)34

(4) CT-P13 (4 ng/ml)32.6

(4) CT-P13 (4 ng/ml)31.2

(4) CT-P13 (4 ng/ml)31.3

(4) CT-P13 (4 ng/ml)33.4

(4) CT-P13 (4 ng/ml)32

(4) CT-P13 (4 ng/ml)35

(4) CT-P13 (4 ng/ml)35.7

(4) CT-P13 (4 ng/ml)30.5

(4) CT-P13 (4 ng/ml)30.4

(4) CT-P13 (4 ng/ml)24.6

(4) CT-P13 (4 ng/ml)28.4

(4) CT-P13 (4 ng/ml)24.5




































(2) CT-P13 (2 ng/ml)22.1

(2) CT-P13 (2 ng/ml)26.6

(2) CT-P13 (2 ng/ml)23.6

(2) CT-P13 (2 ng/ml)22.5

(2) CT-P13 (2 ng/ml)21.2

(2) CT-P13 (2 ng/ml)23.9

(2) CT-P13 (2 ng/ml)20.8

(2) CT-P13 (2 ng/ml)23.2

(2) CT-P13 (2 ng/ml)16.8

(2) CT-P13 (2 ng/ml)20.1

(2) CT-P13 (2 ng/ml)16.9

(2) CT-P13 (2 ng/ml)14.7

(2) CT-P13 (2 ng/ml)17.4

(2) CT-P13 (2 ng/ml)26.5

(2) CT-P13 (2 ng/ml)24

(2) CT-P13 (2 ng/ml)24.4

(2) CT-P13 (2 ng/ml)26.4

(2) CT-P13 (2 ng/ml)26.7

(2) CT-P13 (2 ng/ml)27.5

(2) CT-P13 (2 ng/ml)27.7

(2) CT-P13 (2 ng/ml)25.4

(2) CT-P13 (2 ng/ml)26

(2) CT-P13 (2 ng/ml)26.5

(2) CT-P13 (2 ng/ml)22.1

(2) CT-P13 (2 ng/ml)14.3

(2) CT-P13 (2 ng/ml)20.3

Combined (2)

US RemicadeCT-P13EU Remicade

Sample Lot8 ng/mL4 ng/mL2 ng/mLSample Lot8 ng/mL4 ng/mL2 ng/mL2RMA6010348.333.926.4

CBS13015P112813811912B1C0029191921RMA649014236.923.7

CBM14012P111711811712B1C0031111061112RMA6190545.734.825.3

CHD56013P112512312512B1C00499105983RMKA8070246.642.725.7

CHF59013P110810212312B1C01587811061RMA6580447.340.527.9

CHM62015P111610512512B1C01692971001RMA6131046.235.625.9

CLM91012P112211711612B1C01797881121RMKA871034536.123.8

CKS86016P112011511512B1C0188889983RMA6970150.736.918.6

CBM12011P111510811312B1C0191001051094RMKA8010345.934.319.1

CJM76016P111012011112B1C02010293924RMA6060148.54322.7

DAD96011P111513010012B1C021102971104RMA6930442.135.429.5

14A124P112611410912B1C01297102924RMA6560459.33929.1

ECD18012P112110910212B1C01390100804RMA6490268.941.924.2

ECD19016P113612510912B1C01411196954RMA6870648.142.130.6

14F091P11091199412B1C0061191091145RMKA8050149.838.831.6

14K014P110711112714B1C0011011041034RMA7400132.322.721.9

EJM8201511111110315B4C021001001054RMA7330438.930.222.6

EJM77012P112511012315B1C011071071084RMA7280135.62722.9

DGD53016P11129511515B1C02A1031141094RMA733023527.522.1

FAM12013P111012411615B1C03A1061071155RMKA8050245.331.721.7

14K022P111611812515B1C04A1041171165RMKA8060148.636.731.2

14K013P113812511715B1C05981191064RMA7440239.937.828.4

EKL04012P11139211212B1C0051031031123RMA7050245.63530.2

FBM18012P111110010715B4C01981031155RMA6120138.435.225.7

FBM19014P111911011312B1C007112891135RMKA801013833.722.3

FBM19016P114112610212B1C00897105815RMKA801033630.923.9

EKL04011P19910412815B4C0390911155RMA6110144.93728.1

ELM08016P11131251215RMA611044234.629.1

14M063P11381281214RMKA8160247.433.728

14M064P11391081114RMA7220246.833.328.7

DED38015P1122126136

15A091P1138135150

15A101P1128127142

DDD33013P1143121147

14G054P1132122131

FCL21011P1110122113

Mean120.94116.66118.23Mean100.19100.69104.12

SD11.4910.8712.70SD7.929.2810.36

(+3SD)155.40149.26156.34(+3SD)123.95128.54135.19

(-3SD)86.4884.0580.12(-3SD)76.4372.8573.04

RSD9.49739322889.316223060410.74416790147.90449213239.21743359889.9494118043

JMP format ADCC Cytotox

ManufacturerCytotoxity (%)




































(6) CT-P13 (8 ng/ml)34.6

(6) CT-P13 (8 ng/ml)42.1

(6) CT-P13 (8 ng/ml)37.6

(6) CT-P13 (8 ng/ml)34.9

(6) CT-P13 (8 ng/ml)37

(6) CT-P13 (8 ng/ml)38.9

(6) CT-P13 (8 ng/ml)34.6

(6) CT-P13 (8 ng/ml)39.3

(6) CT-P13 (8 ng/ml)36.8

(6) CT-P13 (8 ng/ml)36.8

(6) CT-P13 (8 ng/ml)36.2

(6) CT-P13 (8 ng/ml)33.3

(6) CT-P13 (8 ng/ml)41.3

(6) CT-P13 (8 ng/ml)42.8

(6) CT-P13 (8 ng/ml)36.4

(6) CT-P13 (8 ng/ml)36.1

(6) CT-P13 (8 ng/ml)51.2

(6) CT-P13 (8 ng/ml)49.3

(6) CT-P13 (8 ng/ml)53.9

(6) CT-P13 (8 ng/ml)52.7

(6) CT-P13 (8 ng/ml)49.7

(6) CT-P13 (8 ng/ml)51

(6) CT-P13 (8 ng/ml)48.5

(6) CT-P13 (8 ng/ml)45.8

(6) CT-P13 (8 ng/ml)30.5

(6) CT-P13 (8 ng/ml)28.3




































(4) CT-P13 (4 ng/ml)28.5

(4) CT-P13 (4 ng/ml)33.1

(4) CT-P13 (4 ng/ml)32.9

(4) CT-P13 (4 ng/ml)26.3

(4) CT-P13 (4 ng/ml)31.5

(4) CT-P13 (4 ng/ml)28.5

(4) CT-P13 (4 ng/ml)29.9

(4) CT-P13 (4 ng/ml)35.3

(4) CT-P13 (4 ng/ml)28.8

(4) CT-P13 (4 ng/ml)30

(4) CT-P13 (4 ng/ml)31.5

(4) CT-P13 (4 ng/ml)31

(4) CT-P13 (4 ng/ml)29.8

(4) CT-P13 (4 ng/ml)34

(4) CT-P13 (4 ng/ml)32.6

(4) CT-P13 (4 ng/ml)31.2

(4) CT-P13 (4 ng/ml)31.3

(4) CT-P13 (4 ng/ml)33.4

(4) CT-P13 (4 ng/ml)32

(4) CT-P13 (4 ng/ml)35

(4) CT-P13 (4 ng/ml)35.7

(4) CT-P13 (4 ng/ml)30.5

(4) CT-P13 (4 ng/ml)30.4

(4) CT-P13 (4 ng/ml)24.6

(4) CT-P13 (4 ng/ml)28.4

(4) CT-P13 (4 ng/ml)24.5




































(2) CT-P13 (2 ng/ml)22.1

(2) CT-P13 (2 ng/ml)26.6

(2) CT-P13 (2 ng/ml)23.6

(2) CT-P13 (2 ng/ml)22.5

(2) CT-P13 (2 ng/ml)21.2

(2) CT-P13 (2 ng/ml)23.9

(2) CT-P13 (2 ng/ml)20.8

(2) CT-P13 (2 ng/ml)23.2

(2) CT-P13 (2 ng/ml)16.8

(2) CT-P13 (2 ng/ml)20.1

(2) CT-P13 (2 ng/ml)16.9

(2) CT-P13 (2 ng/ml)14.7

(2) CT-P13 (2 ng/ml)17.4

(2) CT-P13 (2 ng/ml)26.5

(2) CT-P13 (2 ng/ml)24

(2) CT-P13 (2 ng/ml)24.4

(2) CT-P13 (2 ng/ml)26.4

(2) CT-P13 (2 ng/ml)26.7

(2) CT-P13 (2 ng/ml)27.5

(2) CT-P13 (2 ng/ml)27.7

(2) CT-P13 (2 ng/ml)25.4

(2) CT-P13 (2 ng/ml)26

(2) CT-P13 (2 ng/ml)26.5

(2) CT-P13 (2 ng/ml)22.1

(2) CT-P13 (2 ng/ml)14.3

(2) CT-P13 (2 ng/ml)20.3

JMP format ADCC Cytotox

Cytotoxity (%)

Old

US RemicadeCT-P13

Sample Lot8 ng/mL4 ng/mL2 ng/mLSample Lot8 ng/mL4 ng/mL2 ng/mL

CBS13015P1US- Remicade12813811912B1C002CT-P13919192

CBM14012P1US- Remicade11711811712B1C003CT-P13111106111

CHD56013P1US- Remicade12512312512B1C004CT-P139910598

CHF59013P1US- Remicade10810212312B1C015CT-P138781106

CHM62015P1US- Remicade11610512512B1C016CT-P139297100

CLM91012P1US- Remicade12211711612B1C017CT-P139788112

CKS86016P1US- Remicade12011511512B1C018CT-P13888998

CBM12011P1US- Remicade11510811312B1C019CT-P13100105109

CJM76016P1US- Remicade11012011112B1C020CT-P131029392

DAD96011P1US- Remicade11513010012B1C021CT-P1310297110

14A124P1US- Remicade12611410912B1C012CT-P139710292

ECD18012P1US- Remicade12110910212B1C013CT-P139010080

ECD19016P1US- Remicade13612510912B1C014CT-P131119695

Mean119.92117.23114.15Mean97.4696.1599.62

SD7.6610.197.97SD7.877.579.60

(+3SD)142.92147.80138.06(+3SD)121.07118.86128.40

(-3SD)96.9386.6690.25(-3SD)73.8573.4470.83

RSD6.39112744998.69321458656.97924771728.07491491387.87299180749.6333916206

Old

8 ng/mL

4 ng/mL

2 ng/mL

New

US RemicadeCT-P13

Sample Lot8 ng/mL4 ng/mL2 ng/mLSample Lot8 ng/mL4 ng/mL2 ng/mL

14F091P11091199412B1C006119109114

14K014P110711112714B1C001101104103

EJM8201511111110315B4C02100100105

EJM77012P112511012315B1C01107107108

DGD53016P11129511515B1C02A103114109

FAM12013P111012411615B1C03A106107115

14K022P111611812515B1C04A104117116

14K013P113812511715B1C0598119106

EKL04012P11139211212B1C005103103112

FBM18012P111110010715B4C0198103115

FBM19014P111911011312B1C00711289113

FBM19016P114112610212B1C0089710581

EKL04011P19910412815B4C039091115

ELM08016P1113125121

14M063P1138128121

14M064P1139108111

DED38015P1122126136

15A091P1138135150

15A101P1128127142

DDD33013P1143121147

14G054P1132122131

FCL21011P1110122113

Mean121.55116.32120.64Mean102.92105.23108.62

SD13.3811.4714.44SD7.258.809.36

(+3SD)161.69150.73163.97(+3SD)124.68131.65136.69

(-3SD)81.4181.9177.30(-3SD)81.1778.8280.54

RSD11.00814267259.860872141711.9730073047.04506204398.36719591358.6165871137

Combined

US RemicadeCT-P13EU Remicade

Sample Lot8 ng/mL4 ng/mL2 ng/mLSample Lot8 ng/mL4 ng/mL2 ng/mL8 ng/mL4 ng/mL2 ng/mL

CBS13015P112813811912B1C0029191922RMA6010348.333.926.4

CBM14012P111711811712B1C0031111061111RMA649014236.923.7

CHD56013P112512312512B1C00499105982RMA6190545.734.825.3

CHF59013P110810212312B1C01587811063RMKA8070246.642.725.7

CHM62015P111610512512B1C01692971001RMA6580447.340.527.9

CLM91012P112211711612B1C01797881121RMA6131046.235.625.9

CKS86016P112011511512B1C0188889981RMKA871034536.123.8

CBM12011P111510811312B1C0191001051093RMA6970150.736.918.6

CJM76016P111012011112B1C02010293924RMKA8010345.934.319.1

DAD96011P111513010012B1C021102971104RMA6060148.54322.7

14A124P112611410912B1C01297102924RMA6930442.135.429.5

ECD18012P112110910212B1C01390100804RMA6560459.33929.1

ECD19016P113612510912B1C01411196954RMA6490268.941.924.2

14F091P11091199412B1C0061191091144RMA6870648.142.130.6

14K014P110711112714B1C0011011041035RMKA8050149.838.831.6

EJM8201511111110315B4C021001001054RMA7400132.322.721.9

EJM77012P112511012315B1C011071071084RMA7330438.930.222.6

DGD53016P11129511515B1C02A1031141094RMA7280135.62722.9

FAM12013P111012411615B1C03A1061071154RMA733023527.522.1

14K022P111611812515B1C04A1041171165RMKA8050245.331.721.7

14K013P113812511715B1C05981191065RMKA8060148.636.731.2

EKL04012P11139211212B1C0051031031124RMA7440239.937.828.4

FBM18012P111110010715B4C01981031153RMA7050245.63530.2

FBM19014P111911011312B1C007112891135RMA6120138.435.225.7

FBM19016P114112610212B1C00897105815RMKA801013833.722.3

EKL04011P19910412815B4C0390911155RMKA801033630.923.9

ELM08016P11131251215RMA6110144.93728.1

14M063P11381281215RMA611044234.629.1

14M064P11391081114RMKA8160247.433.728

DED38015P11221261364RMA7220246.833.328.7

15A091P1138135150

15A101P1128127142

DDD33013P1143121147

14G054P1132122131

FCL21011P1110122113

Mean120.94116.66118.23Mean100.19100.69104.12

SD11.4910.8712.70SD7.929.2810.36

(+3SD)155.40149.26156.34(+3SD)123.95128.54135.19

(-3SD)86.4884.0580.12(-3SD)76.4372.8573.04

RSD9.49739322889.316223060410.74416790147.90449213239.21743359889.9494118043

JMP Format

Manufacturer8 ng/mL4 ng/mL2 ng/mL

US-Remicade128138119













US-Remicade10911994




US-Remicade11295115




US-Remicade11392112




US-Remicade99104128










CT-P13919192

CT-P13111106111

CT-P139910598

CT-P138781106

CT-P139297100

CT-P139788112

CT-P13888998

CT-P13100105109

CT-P131029392

CT-P1310297110

CT-P139710292

CT-P139010080

CT-P131119695

CT-P13119109114

CT-P13101104103

CT-P13100100105

CT-P13107107108

CT-P13103114109

CT-P13106107115

CT-P13104117116

CT-P1398119106

CT-P13103103112

CT-P1398103115

CT-P1311289113

CT-P139710581

CT-P139091115

JMP Format

8 ng/mL

4 ng/mL

2 ng/mL

JMP format ADCC Potency

ManufacturerRelative Potency (%)




































(6) CT-P13 (8 ng/ml)91

(6) CT-P13 (8 ng/ml)111

(6) CT-P13 (8 ng/ml)99

(6) CT-P13 (8 ng/ml)87

(6) CT-P13 (8 ng/ml)92

(6) CT-P13 (8 ng/ml)97

(6) CT-P13 (8 ng/ml)88

(6) CT-P13 (8 ng/ml)100

(6) CT-P13 (8 ng/ml)102

(6) CT-P13 (8 ng/ml)102

(6) CT-P13 (8 ng/ml)97

(6) CT-P13 (8 ng/ml)90

(6) CT-P13 (8 ng/ml)111

(6) CT-P13 (8 ng/ml)119

(6) CT-P13 (8 ng/ml)101

(6) CT-P13 (8 ng/ml)100

(6) CT-P13 (8 ng/ml)107

(6) CT-P13 (8 ng/ml)103

(6) CT-P13 (8 ng/ml)106

(6) CT-P13 (8 ng/ml)104

(6) CT-P13 (8 ng/ml)98

(6) CT-P13 (8 ng/ml)103

(6) CT-P13 (8 ng/ml)98

(6) CT-P13 (8 ng/ml)112

(6) CT-P13 (8 ng/ml)97

(6) CT-P13 (8 ng/ml)90




































(4) CT-P13 (4 ng/ml)91

(4) CT-P13 (4 ng/ml)106

(4) CT-P13 (4 ng/ml)105

(4) CT-P13 (4 ng/ml)81

(4) CT-P13 (4 ng/ml)97

(4) CT-P13 (4 ng/ml)88

(4) CT-P13 (4 ng/ml)89

(4) CT-P13 (4 ng/ml)105

(4) CT-P13 (4 ng/ml)93

(4) CT-P13 (4 ng/ml)97

(4) CT-P13 (4 ng/ml)102

(4) CT-P13 (4 ng/ml)100

(4) CT-P13 (4 ng/ml)96

(4) CT-P13 (4 ng/ml)109

(4) CT-P13 (4 ng/ml)104

(4) CT-P13 (4 ng/ml)100

(4) CT-P13 (4 ng/ml)107

(4) CT-P13 (4 ng/ml)114

(4) CT-P13 (4 ng/ml)107

(4) CT-P13 (4 ng/ml)117

(4) CT-P13 (4 ng/ml)119

(4) CT-P13 (4 ng/ml)103

(4) CT-P13 (4 ng/ml)103

(4) CT-P13 (4 ng/ml)89

(4) CT-P13 (4 ng/ml)105

(4) CT-P13 (4 ng/ml)91




































(2) CT-P13 (2 ng/ml)92

(2) CT-P13 (2 ng/ml)111

(2) CT-P13 (2 ng/ml)98

(2) CT-P13 (2 ng/ml)106

(2) CT-P13 (2 ng/ml)100

(2) CT-P13 (2 ng/ml)112

(2) CT-P13 (2 ng/ml)98

(2) CT-P13 (2 ng/ml)109

(2) CT-P13 (2 ng/ml)92

(2) CT-P13 (2 ng/ml)110

(2) CT-P13 (2 ng/ml)92

(2) CT-P13 (2 ng/ml)80

(2) CT-P13 (2 ng/ml)95

(2) CT-P13 (2 ng/ml)114

(2) CT-P13 (2 ng/ml)103

(2) CT-P13 (2 ng/ml)105

(2) CT-P13 (2 ng/ml)108

(2) CT-P13 (2 ng/ml)109

(2) CT-P13 (2 ng/ml)115

(2) CT-P13 (2 ng/ml)116

(2) CT-P13 (2 ng/ml)106

(2) CT-P13 (2 ng/ml)112

(2) CT-P13 (2 ng/ml)115

(2) CT-P13 (2 ng/ml)113

(2) CT-P13 (2 ng/ml)81

(2) CT-P13 (2 ng/ml)115

JMP format ADCC Potency

Relative Potency (%)

Summary Table

8 ng/mL (Mean)4 ng/mL (mean)2 ng/mL (mean)8 ng/mL (RSD)4 ng/mL (RSD)2 ng/mL (RSD)

US Remicade- Original Data119.9230769231117.2307692308114.15384615386.39112744998.69321458656.9792477172

US Remicade- New Data121.5454545455116.3181818182120.636363636411.00814267259.860872141711.973007304

US Remicade- Combined Data120.9428571429116.6571428571118.22857142869.49739322889.316223060410.7441679014

% Change from original to new1.35%-0.78%5.68%72.24%13.43%71.55%

% change from original to combined0.85%-0.49%3.57%48.60%7.17%53.94%

CT-P13- Original Data97.461538461596.153846153899.61538461548.07491491387.87299180749.6333916206

CT-P13- New Data102.9230769231105.2307692308108.61538461547.04506204398.36719591358.6165871137

CT-P13- Combined Data100.1923076923100.6923076923104.11538461547.90449213239.21743359889.9494118043

% Change from original to new5.60%9.44%9.03%-12.75%6.28%-10.56%

% change from original to combined2.80%4.72%4.52%-2.11%17.08%3.28%

Summary Table

US Remicade- Original Data

US Remicade- New Data

US Remicade- Combined Data

Simplified

AC Cytotox

US Licensed RemicadeCT-P13EU Licensed Remicade8

3.528.6722.111.526.4

3.5287.526.611.523.7

429.9723.611.525.3

4.526.1722.51225.7

426.67.521.21227.9

4.524.7723.91225.9

4.524.4720.81223.8

3.5247.523.212.518.6

3.520.37.516.81219.1

4.518.3820.11122.7

419.9716.911.529.5

4.518.6714.71229.1

320717.41224.2

324.77.526.512.530.6

432.47241231.6

4.525.27.524.412.521.9

428.6826.411.522.6

424.9826.71222.9

325.1827.512.522.1

427.1827.71221.7

525.4825.41231.2

4.525.48261228.4

424.4826.51130.2

325.7822.11125.7

3.523.3814.31122.3

3.527.1820.31123.9

525.62328.51128.1

528.72333.11129.1

526.32332.91128

532.32326.31128.7

532.42331.52733.9

530.72328.52736.9

531.82329.92734.8

527.92335.32742.7

523.92328.82740.5

1943.123302735.6

1936.92331.52736.1

19.538.523.5312736.9

203323.529.82734.3

20.534.123.53427.543

20.537.923.532.627.535.4

20.538.823.531.227.539

20.536.223.531.327.541.9

2037.223.533.427.542.1

2040.223.53227.538.8

1935.3243527.522.7

19.533.82435.727.530.2

19.538.52430.527.527

19.541.92430.427.527.5

20.536.82424.627.531.7

1932.52428.42836.7

19.534.42424.52837.8

2028.737.534.62835

20.537.237.542.12835.2

20.535.437.537.62833.7

20.537.837.534.928.530.9

20.528.237.53728.537

1930.737.538.928.534.6

1933.837.534.628.533.7

2038.73839.328.533.3

2030.43836.84248.3

2036.43836.84242

2037.83836.24245.7

2031.73833.34246.6

1937.23841.34247.3

2038.83842.84246.2

2036.538.536.44245

2034.938.536.14250.7

19.53338.551.242.545.9

2033.138.549.342.548.5

3548.838.553.942.542.1

34.544.338.552.742.559.3

34.547.43949.742.568.9

34.543.5395142.548.1

3546.83948.542.549.8

34.549.33945.842.532.3

3546.93930.542.538.9

35.544.93928.342.535.6

3539.64335

3441.54345.3

34.5474348.6

3544.94339.9

3550.74345.6

3557.94338.4

34.559.14338

3553.243.536

354543.544.9

34.544.843.542

3543.943.547.4

34.546.443.546.8

3555

34.544.5

3543.5

34.546.4

3555.3

3538.5

34.544.1

34.547

3547.2

3541.3

3547.5

34.544.1

3549.3

3444.1

3436.7

AC Cytotox


CT-P13


Absolute Cytotoxicity (%)

Biosimilars for IBD: What the Gastroenterologist Needs to KnowDisclosuresWhat Questions Do Clinicians Have?What Questions Do Clinicians Have?Biosimilarity: DefinitionFramework to consider what Biosimilar meansSlide Number 7What Questions Do Clinicians Have?Stepwise Approach to Demonstrating Similarity Extrapolation Scientific JustificationExtrapolation Example Slide Number 13PK / BiodistributionImmunogenicityToxicity Extrapolation SummaryWhat Questions Do Clinicians Have?Impact of Immunogenicity Interchangeability: DefinitionConclusionsResources: Additional SlidesQR Analysis: PBMC ADCCQR Analysis: NK-ADCC CytotoxicityFDA EMA slide.pdfSlide Number 1

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