Biosimilars 101: How similar are they? Matthew Marston, Pharm.D., - - PDF document

▶
biosimilars 101 how similar are they
SMART_READER_LITE
LIVE PREVIEW

Biosimilars 101: How similar are they? Matthew Marston, Pharm.D., - - PDF document

Aug 15, 2022 322 likes •495 views

3/20/2018 Biosimilars 101: How similar are they? Matthew Marston, Pharm.D., BCPS, BCOP Senior Manager of Clinical Pharmacy Services Miller Drug, LLC Outline Describe the approval and manufacturing process of biologics Identify

slide-1
SLIDE 1

3/20/2018 1

Biosimilars 101: How “similar” are they?

Matthew Marston, Pharm.D., BCPS, BCOP Senior Manager of Clinical Pharmacy Services Miller Drug, LLC

  • Describe the approval and manufacturing

process of biologics

  • Identify differences between generics and

biosimilars

  • Describe financial and operational

implications for oncology practices

Outline

slide-2
SLIDE 2

3/20/2018 2

Review of Biologics

  • Hospira. http://www.hospira.co.uk/en/about_hospira/biologics/biosimilars_generic_drugs. Accessed 4/1/2016.
  • Examples:
  • Aspirin
  • Warfarin
  • Gabapentin
  • Made through chemical

reactions

  • Easily reproduced
  • Identical active

ingredient

Small Molecules Biologics

  • Examples:
  • Filgrastim
  • Rituximab
  • Cetuximab
  • Made from a variety of

natural sources

  • Human, animal, or

microorganism

  • Complex (proprietary)

manufacturing process

  • Variability is unavoidable
slide-3
SLIDE 3

3/20/2018 3

Biologic Manufacturing

D’Haens, GR, et al. Journal of Crohn’s and Colitis (2014) 8, 726‐34.

  • Significant variations in

potency exist between lots

  • FDA requires notification
  • f any change in

manufacturing

  • Variations are not

thought to produce clinically meaningful differences

Natural Protein Variation

slide-4
SLIDE 4

3/20/2018 4

“The ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human or animal.”

Immunogenicity

Kahn FA. CRC Press, 2011; 518.

http://bcn2012.europeanbioanalysisforum.eu/slides/day%202/ii%20biosimilars/4_sauerborn.pdf

slide-5
SLIDE 5

3/20/2018 5

  • Rising cost negatively impacts patient access
  • European study demonstrated a direct

relationship between GDP and biologic use

  • Biosimilar competition in US expected to

produce $250 billion in cost savings from 2014 to 2024

Cost of Biologics

  • 1. Péntek M, et al. Eur J Health Econ 2014; 15(suppl 1):S35‐43.
  • 2. Express Scripts. http://lab.express‐scripts.com/lab/insights/industry‐updates/the‐$250‐billion‐potential‐of‐
  • biosimilars. Accessed 4/1/2016

http://www.sandoz‐biosimilars.com/en/biosimilars/why‐biologics‐matter‐en.shtml

slide-6
SLIDE 6

3/20/2018 6

Ventola, C. P&T. 2013; 38(5):270‐87.

“A biosimilar product is a biological product that is approved based on a showing that it is highly similar to an FDA‐approved biological product, known as a reference product, and has no clinically meaningful differences in terms of safety and effectiveness from the reference product.”

What is a Biosimilar?

FDA.http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/A pprovalApplications/TherapeuticBiologicApplications/Biosimilars/. Accessed 4/1/2016.

slide-7
SLIDE 7

3/20/2018 7

  • Biologics Price Competition and

Innovation Act of 2009 (BPCI Act)

  • Part of the Affordable Care Act
  • Signed into law on March 23, 2010
  • 1st biosimilar filgrastim-sndz (Zarxio)

approved in US on March 6, 2015

Biosimilars in the U.S.

FDA Approval Process

Christl, L. FDA. FDA.gov. Accessed April 7, 2016.

slide-8
SLIDE 8

3/20/2018 8 STRUCTURE

McCamish M, Woollett G. Clin Pharm & Ther. 2012; 91(3); 405‐17

FUNCTION

McCamish M, Woollett G. Clin Pharm & Ther. 2012; 91(3); 405‐17

slide-9
SLIDE 9

3/20/2018 9

McCamish M, Woollett G. Clin Pharm & Ther. 2012; 91(3); 405‐17

PK & PD

McCamish M, Woollett G. Clin Pharm & Ther. 2012; 91(3); 405‐17

EFFICACY & SAFETY

slide-10
SLIDE 10

3/20/2018 10

  • Quintiles. http://www.quintiles.com/microsites/biosimilars‐knowledge‐connect/regulatory‐requirements. Accessed 4/1/2016.

Reference Product (Trade Name) Manufacturer Biosimilar Manufacturer Biosimilar’s Availability on the U.S. Market

Adalimumab (Humira) Abbvie Adalimumab‐adbm (Cyltezo) Adalimumab‐atto (Amjevita) Boehringer Ingelheim Amgen Unavailable Unavailable (delayed until 2023) Bevacizumab (Avastin) Genentech Bevacizumab‐awwb (Mvasi) Genentech Unavailable Etanercept (Enbrel) Amgen Etanercept‐szzs (Erelzi) Sandoz Unavailable Filgrastim (Neupogen) Amgen Filgrastim‐sndz (Zarxio) Sandoz Available Infliximab (Remicade) Janssen Infliximab‐abda (Renflexis) Infliximab‐dyyb (Inflectra) Infliximab‐qbtx (Ixifi) Merck Pfizer Pfizer Available Available Unavailable Trastuzumab (Herceptin) Genentech /Roche Trastuzumab‐dkst (Ogivri) Mylan / Biocon Unavailable

slide-11
SLIDE 11

3/20/2018 11

“Extrapolation”

  • The FDA may extrapolate approval to indications other

than what was studied

  • “Sufficient scientific justification” required for each

indication

  • Example: Infliximab
  • Studied in rheumatoid arthritis and ankylosing spondylitis
  • FDA recently approved biosimilar Inflectra across all

infliximab indications

Other Biosimilar Concepts

“Interchangeability”

  • Requires additional crossover design trials
  • Allows pharmacists to interchange without physician

approval

  • Trials conducted in Europe indicate interchanging

therapies results in no added risk of immunogenicity

Other Biosimilar Concepts

slide-12
SLIDE 12

3/20/2018 12

  • Should demonstrate efficacy and safety, including lack of

immunogenicity.

  • Establish a transparent regulatory pathway for approval of

biosimilars.

  • Physician choice between biologic products should not be

restricted.

  • Biosimilars should be subject to careful post-market safety

surveillance.

  • Interchangeability should be established by clinical trials.
  • Congress should ensure adequate FDA funding to meet new

demands.

2015 ASCO Policy Brief

Lyman, GH. ASCO. 2017. https://am.asco.org/biosimilars‐changing‐cancer‐care‐landscape.

  • 2017 Pfizer vs. J&J – infliximab biosimilar
  • First litigation on biosimilars
  • Alleged anticompetitive contracts
  • Possibly linked to slow biosimilar market

development

  • High development cost
  • Generic drug $1-5 million vs. biosimilar ~$250

million

  • Lack of understanding in U.S. market

Challenges to Biosimilars

slide-13
SLIDE 13

3/20/2018 13

  • Reference product dispensed

when biosimilar is preferred

  • Biosimilar dispensed when

reference product is preferred

  • Biosimilar or reference

product dispensed prior to

  • btaining authorization
  • Authorization for one

product obtained and the

  • ther is dispensed

Payment Pitfalls

  • Naming convention:
  • Generic name plus manufacturer suffix
  • E.g. filgrastim-sndz
  • Many sites choosing to utilize brand names
  • Limiting number of formulary products
  • Inpatient vs. Outpatient
  • Medication reconciliation
  • Need for pharmacovigilance

Medication Safety

slide-14
SLIDE 14

3/20/2018 14

  • Treatment vs. Supportive Care vs. Palliative
  • Problem with extrapolation?
  • Ex. Trastuzumab, bevacizumab, cetuximab
  • Plant–Made Biologics (PMBs)
  • Low production cost
  • Low risk of pathogen contamination
  • Ex. Zmapp, Elelyso

On The Horizon

Chen Q. F1000Res. 2016; 5: F1000 Faculty Rev‐912.

  • Biosimilars offer an opportunity to lower the

cost of biologic therapies

  • Biosimilars are more complex than generics
  • Significant barriers to market entry currently

exist

  • Careful consideration must be made prior to

administering therapy to avoid losses in reimbursement

Conclusions

slide-15
SLIDE 15

3/20/2018 15

Biosimilars 101: How “similar” are they?

Matthew Marston, Pharm.D., BCPS, BCOP Senior Manager of Clinical Pharmacy Services Miller Drug, LLC

  • Chen Q. The potential of plants as a system for the development and production of human
  • biologics. F1000Res. 2016; 5: F1000 Faculty Rev‐912.
  • Christl L. FDA. FDA’s Overview of the Regulatory Guidance for the Development and Approval
  • f Biosimilar Products in the US. FDA. FDA.gov. Accessed April 7, 2016.
  • D’Haens GR, et al. Future directions in inflammatory bowel disease management. Journal of

Crohn’s and Colitis (2014) 8, 726‐34.

  • Dörner T, et al. The hanging landscape of biosimilars in rheumatology. Ann Rheum Dis

2016;0:1‐9.

  • Express Scripts. The $250 billion potential of biosimilars. http://lab.express‐

scripts.com/lab/insights/industry‐updates/the‐$250‐billion‐potential‐of‐biosimilars. Accessed 4/1/2016.

  • FDA. Information on biosimilars.

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApprov ed/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/. Accessed 4/1/2016.

  • Hospira. Biosimilars Compared to Generic Drugs.

http://www.hospira.co.uk/en/about_hospira/biologics/biosimilars_generic_drugs. Accessed 4/1/2016.

slide-16
SLIDE 16

3/20/2018 16

  • Kahn FA. Biotechnology Fundamentals. CRC Press, 2011; 518.
  • Lai Z, La Noce A. Key design considerations on comparative clinical efficacy studies for

biosimilars: adalimumab as an example. RMD Open. 2016; 2(1): e000154.

  • Lyman, GH. Biosimilars in the Changing Cancer Care Landscape . ASCO. 2017.

https://am.asco.org/biosimilars‐changing‐cancer‐care‐landscape.

  • McCamish M, Woollett G. The State of the Art in the Development of Biosimilars. Clin Pharm

& Ther. 2012; 91(3); 405‐17.

  • Péntek M, et al. Patients’ access to biological therapy in chronic inflammatory conditions; per

capita GDP does not explain the intercountry differences. Eur J Health Econ 2014; 15(suppl 1):S35‐43.

  • Sandoz. http://www.sandoz‐biosimilars.com/en/biosimilars/why‐biologics‐matter‐en.shtml.

Accessed 4/1/2016.

  • Schiestl M, et al. Acceptable changes in quality attributes of glycosylated biopharmaceuticals.

Nature Biotechnology (2011) 29, 310‐12.

  • Ventola C. Biosimilars Part 1: Proposed Regulatory Criteria for FDA Approval. P&T. 2013;

38(5):270‐87.