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Biosimilar Monoclonal
Antibodies: Experience of
Galway University Hospitals
Prof. LJ Egan
Disclosures
• Research support from:
• MSD
• AbbVie
• Unrestricted educational grants from:
• Takeda
• Shire
• AbbVie
• Ho...
Biosimilars: increasing pace of development
Scientific Advice Requested from EMA by Biosimilars Companies
Schneider et al,...
Biosimilar Monoclonal Antibodies EMA
framework: 2012
FDA process for Biosimilar MAbs
• Highly similar to originator with respect to physicochemical properties
• No clinically ...
General requirements for FDA approval
• Biosimilarity
• Same Mechanism of action
• Analytical studies
• Animal studies
• C...
Extrapolation of indications: considerations
• Mechanism of action the same?
• Pharmacokinetic biodistribution the same?
•...
Anti-TNFs on the Top of Biologicals Sales
INN EU patent
exp date
US patent
exp date
Biosimilars in
development *
Adalimuma...
Infliximab
• Chimeric mouse-human Mab
• Potently and specifically
neutralizes TNFα
• Dampens inflammation
• Licensed Indic...
Infliximab
• Problems with its use
• Expense
• Life threatening infusion reactions
(rare)
• Loss of response
• Common side...
Pharmacokinetic Profile
PLANET AS
Park et al, Ann Rheum Dis 2012;71 (Suppl 3):111
n= 221
Safety - Infections
Treatment-Emergent Infections reported for at least 1% of patients
Remsima
5 mg/kg (n = 128)
Inflixima...
Efficacy Secondary Endpoint
N=220
PLANET AS
Park et al, Ann Rheum Dis 2012;71 (Suppl 3):111
PLANET RA – Primary Endpoint:
Equivalence by Clinical Response at Week 30
Yoo et al, Ann Rheum Dis 2012;71 (Suppl 3):359
CT-P13 Open Label Extension Trials in RA and AS
• Open label extension, all pts receiving CT-P13
• Approx. 66% entering OL...
Continued CT-P13 vs Switching From Remicade to CT-
P13 in PLANET-RA
Yoo et al. ACR 2013, L1
76.8
45.7
21.9
71.5
48.3
24.5
...
EMA approval of biosimilar infliximab
On 27 June 2013, the Committee for Medicinal Products for Human
Use (CHMP) adopted a...
European Crohn’s and Colitis Organization:
Position statement on biosimilar medications
GUH response
• Can biosimilar IFX provide advantages for our patients and hospital?
• Rheumatoid patients already on infli...
GUH
• Tertiary referral centre for the west
of Ireland
• Extensive use of biological drugs
across a host of indications
• ...
GUH Drug and Therapeutics committee
Galway University Hospitals (GUH)
Drug and Therapeutics Committee
Terms of Reference
T...
Introduction of Biosimilar monoclonal
antibodies in practice: Issues
• Chequered history of biosimilar recombinant protein...
GUH Drug and Therapeutics committee:
Introduction of Biosimilar Medicines Policy
TITLE: Policy for the Use of Biosimilar M...
GUH Biosimilar Medicines Policy
• Purpose
• The purpose of this policy is to provide guidance and a standardised
methodolo...
GUH Biosimilar Medicines Policy: checklist
Yes No
Is the biosimilar under consideration licensed by the EMA/IMB for its
in...
Introduction of Biosimilar Infliximab at GUH
• Rheumatology Patients
• Consultants satisfied with Switch data
• Patients a...
Introduction of Biosimilar Infliximab at GUH
• Inflammatory bowel disease patients
• Consultants not confident in lack of ...
GUH: Use of biological drugs in chronic
inflammatory bowel disease
• Current usage data
IBD 2015 2014 2013 2012 2011
vials...
GUH: Use of biological drugs in chronic
inflammatory bowel disease
• Results of biosimilar infliximab at GUH
• Too few pat...
Conclusions
• Successful introduction of biosimilar infliximab at GUH
• Different approach for rheumatic and IBD patients ...
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Biologics & Biosimilars - Prof Larry Egan - April 5th, 2016

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Professor Larry Egan of NUI Galway provides a clinical perspective on biologic and biosimilar medicines.

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Biologics & Biosimilars - Prof Larry Egan - April 5th, 2016

  1. 1. Biosimilar Monoclonal Antibodies: Experience of Galway University Hospitals Prof. LJ Egan
  2. 2. Disclosures • Research support from: • MSD • AbbVie • Unrestricted educational grants from: • Takeda • Shire • AbbVie • Hospira
  3. 3. Biosimilars: increasing pace of development Scientific Advice Requested from EMA by Biosimilars Companies Schneider et al, Nat Biotechnol 2012:30:1179-85
  4. 4. Biosimilar Monoclonal Antibodies EMA framework: 2012
  5. 5. FDA process for Biosimilar MAbs • Highly similar to originator with respect to physicochemical properties • No clinically significant differences in “most sensitive” disease • Specific regulatory pathway: • Abbreviated licensure pathway • Needs to demonstrate “Biosimilarity” • Biosimilar • Highly similar not withstanding minor differences in clinically inactive components And • No clinically significant differences • Not the same as interchangeability
  6. 6. General requirements for FDA approval • Biosimilarity • Same Mechanism of action • Analytical studies • Animal studies • Clinical studies • Pharmacokinetic • Pharmacodynamic • Immunogenicity • Clinical efficacy in one indication
  7. 7. Extrapolation of indications: considerations • Mechanism of action the same? • Pharmacokinetic biodistribution the same? • Immunogenicity in different populations? • Toxicity in different populations?
  8. 8. Anti-TNFs on the Top of Biologicals Sales INN EU patent exp date US patent exp date Biosimilars in development * Adalimumab 2018 2016 13 Etanercept 2015 2028 21 Infliximab 2014 2018 9 Insulin Glargine 2014 2014 5 Rituximab 2013 2016 30 Bevacizumab 2019 2017 14 Interferon B-1a Expired Expired N/A Trastuzumab 2015 2015 N/A Insulin Aspart 2014 2019 N/A Glatiramer acet 2017 2015 N/A Pegfilgrastim 2015 2014 14 Ranibizumab 2016 2016 2 8.1 7.3 7.1 6.2 5.9 5.3 5 5 4.9 4.3 4.3 4 0 5 10 global sales, USD billion Source: IMS MIDAS, 09/2012, IMS Patent focus, Adapted from G. Morelli, IMS Health *Rader RA, Biosimilars markets. BioProcess International 2013;11(6)suppl:16-23 Total USD 67 billion
  9. 9. Infliximab • Chimeric mouse-human Mab • Potently and specifically neutralizes TNFα • Dampens inflammation • Licensed Indications • Rheumatoid arthritis • Ankylosing spondylitis • Psoriatic arthritis • Psoriasis • Ulcerative colitis • Crohn’s disease • Paediatric UC and CD
  10. 10. Infliximab • Problems with its use • Expense • Life threatening infusion reactions (rare) • Loss of response • Common side effects • Infections • Skin reactions • Rare side effects • CNS demyelination • Cancers (?) Infliximab Human Fc Region Mouse FAB Arm Adalimumab Certolizumab pegol Human Fc Region VH VL CL CH CL Mouse FAB Region Human FAB Arm Human Fc Region Human FAB Arm Golimumab
  11. 11. Pharmacokinetic Profile PLANET AS Park et al, Ann Rheum Dis 2012;71 (Suppl 3):111 n= 221
  12. 12. Safety - Infections Treatment-Emergent Infections reported for at least 1% of patients Remsima 5 mg/kg (n = 128) Infliximab 5 mg/kg (n = 122) Total No. of patient with infection and infestation 55 49 -15 -10 -5 0 5 10 15 Bacteriuria Bronchitis Cervicitis Herpes simplex Influenza Latent tuberculosis Nasopharyngitis Oral herpes Pharyngitis Respiratory tract infection Rhinitis Sinusitis Tinea pedis Tonsillitis Upper respiratory tract infection Urinary tract infection Viral upper respiratory tract infection Number of Events Park W et al. Ann Rheum Dis 2013 PLANET AS
  13. 13. Efficacy Secondary Endpoint N=220 PLANET AS Park et al, Ann Rheum Dis 2012;71 (Suppl 3):111
  14. 14. PLANET RA – Primary Endpoint: Equivalence by Clinical Response at Week 30 Yoo et al, Ann Rheum Dis 2012;71 (Suppl 3):359
  15. 15. CT-P13 Open Label Extension Trials in RA and AS • Open label extension, all pts receiving CT-P13 • Approx. 66% entering OLE Posters presented as late breaking abstracts at ACR CT-P13 Remicade R Wk 0 Wk 102Wk 54 Double-blind Open label extension Continue CT-P13 Switch to CT-P13
  16. 16. Continued CT-P13 vs Switching From Remicade to CT- P13 in PLANET-RA Yoo et al. ACR 2013, L1 76.8 45.7 21.9 71.5 48.3 24.5 72.2 48.3 24.5 77.5 50. 23.9 78.2 47.9 29.6 71.8 51.4 26.1 0. 10. 20. 30. 40. 50. 60. 70. 80. 90. ACR20 ACR50 ACR70 ACR20 ACR50 ACR70 ACR20 ACR50 ACR70 CT-P13 maintenance (n=158) Remicade to CT-P13 (n=144) Wk 78 Wk 102 Percentofpatients(%) Wk 52
  17. 17. EMA approval of biosimilar infliximab On 27 June 2013, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Inflectra (and Remsima), 100 mg powder for concentrate for solution for infusion intended for the treatment of rheumatoid arthritis, adult Crohn’s disease, paediatric Crohn’s disease, ulcerative colitis, paediatric ulcerative colitis, ankylosing spondylitis, psoriatic arthritis and psoriasis.
  18. 18. European Crohn’s and Colitis Organization: Position statement on biosimilar medications
  19. 19. GUH response • Can biosimilar IFX provide advantages for our patients and hospital? • Rheumatoid patients already on infliximab? • Rheumatoid patient starting infliximab? • IBD patients? • Concerns that no published data on use of biosimilar infliximab in IBD • What are the cost implications of adopting biosimilar infliximab for some or all of our patients at GUH?
  20. 20. GUH • Tertiary referral centre for the west of Ireland • Extensive use of biological drugs across a host of indications • Chronic inflammatory diseases • Inflammatory bowel disease • Inflammatory arthritis • Psoriasis • Cancer • Haematological • Solid tumours • Administration setting • Outpatient infusions unit • Haematology/Oncology day ward • Increasing cost of biological drugs
  21. 21. GUH Drug and Therapeutics committee Galway University Hospitals (GUH) Drug and Therapeutics Committee Terms of Reference Title The committee will be known as the Galway University Hospitals Drug and Therapeutics Committee Purpose and Objectives of the Committee. To ensure the safe, rational and cost-effective use of medicines in GUH.
  22. 22. Introduction of Biosimilar monoclonal antibodies in practice: Issues • Chequered history of biosimilar recombinant proteins • Eprex recombinant erythropoietin • Pure red cell aplasia • Efficacy long term • Safety long term • Supply • Pharmacovigilence • Extrapolation of indications • Physician autonomy • Impact on cost savings due to vial sharing
  23. 23. GUH Drug and Therapeutics committee: Introduction of Biosimilar Medicines Policy TITLE: Policy for the Use of Biosimilar Medicines in Galway University Hospitals REFERENCE NO: CLN-PHAR/UCH-091 REVISION NO: 1 OWNER: Andrew Barber AUTHOR: Tom Walsh, Andrew Barber APPROVED BY: Andrew Barber Page 1 of 6 EFFECTIVE FROM: 6th March 2014 REVIEW DATE: 6th March 2016
  24. 24. GUH Biosimilar Medicines Policy • Purpose • The purpose of this policy is to provide guidance and a standardised methodology for the safe introduction and use of licensed biosimilar medicines in GUH. It is important that clinicians should have confidence when prescribing biosimilars for all their licensed indications
  25. 25. GUH Biosimilar Medicines Policy: checklist Yes No Is the biosimilar under consideration licensed by the EMA/IMB for its intended indication? Is there at least one published (or submitted) randomised comparative clinical study, using hard clinical outcomes that demonstrates equivalence with the reference product? Was human safety (including immunogenicity) data required and provided for the biosimilar’s approval? Is the clinician/specialist satisfied based on the totality of evidence, that the biosimilar has demonstrated similarity in nature to the reference product, in terms of quality, efficacy and safety? Have the full projected savings/costs for the hospital been assessed and outlined for the DTC? Are prescribers aware that prescribing of biosimilars is by brand (or trade) name only? Will the reference product remain available to clinicians if needed in exceptional circumstances? Is Pharmacy satisfied with the post-licensing surveillance requirements of the new product? Is Pharmacy satisfied with the supply arrangements for the new biosimilar? Is Pharmacy satisfied with the new product packaging, labelling and patient/product information?
  26. 26. Introduction of Biosimilar Infliximab at GUH • Rheumatology Patients • Consultants satisfied with Switch data • Patients asked for agreement to switch • All (approximately 40) agreed • All switched to biosimilar infliximab in 2014
  27. 27. Introduction of Biosimilar Infliximab at GUH • Inflammatory bowel disease patients • Consultants not confident in lack of data on IBD patients • Agreed to start new infliximab patients on biosimilar for a trial period • No obvious problems arose • Continued since • No patients switched from the originator
  28. 28. GUH: Use of biological drugs in chronic inflammatory bowel disease • Current usage data IBD 2015 2014 2013 2012 2011 vials vials vials vials vials REMICADE 100MG 1729 1973 1669 1442 1219 INFLECTRA 100MG 695 88 Total 2424 2061 1669 1442 1219 RHEUMATOLOGY vials vials vials vials vials REMICADE 100MG 16 145 663 633 694 INFLECTRA 100MG 1079 706 Total 1095 851 663 633 694 OVERALL 3519 2912 2332 2075 1913
  29. 29. GUH: Use of biological drugs in chronic inflammatory bowel disease • Results of biosimilar infliximab at GUH • Too few patients to detect differences in • Efficacy • Safety • Subsequent recommendation of approval of biosimilar infliximab for all 7 indications by FDA advisory panel • Subsequent adoption of biosimilar infliximab by several other Irish hospitals • Subsequent approval for funding by Irish private health insurers
  30. 30. Conclusions • Successful introduction of biosimilar infliximab at GUH • Different approach for rheumatic and IBD patients based on availability of clinical data • Key role of prescribing consultants • Supported by a policy adopted by the hospital Drug and Therapeutics committee • Pharmacovigilance maintained • Increased usage of infliximab

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