This presentation was developed by the Government & Industry Affairs Committee of the Crohn s & Colitis Foundation of America

This presentation was developed by the Government & Industry Affairs Committee of the Crohn s & Colitis Foundation of America

The development of this presentation was supported in 2016 by a sponsorship from AbbVie, Inc. and an educational grant from Amgen. Additional support is provided through CCFA s annual giving programs and donors.

Speaker Richard P. Rood, MD, FACP, FACG, AGAF, FASGE Medical Director, IBD Program Associate Professor of Clinical Medicine University of Cincinnati College of Medicine

Needs of Patients with Inflammatory bowel diseases (IBD) Cures Prevention strategies More research High quality and available care More therapies Medical options for patients who don t respond to therapy Medical options for patients who lose response to therapy Affordable medical care

Medical Treatment Options for IBD Antibiotics Aminosalicylates Oral 5-ASA therapies Rectal therapies Steroids Prednisone Budesonide Immunomodulators Azathioprine, 6- mercaptopurine methotrexate Biological therapies Anti-TNF therapies Anti-integrin therapies Interleukin-12 and 23 antagonists

What are Biologics Biologics are made of complex proteins and some are made to target the immune system Biologics are not the same as simple medicines Conventional medicines can have identical copies made (these are called generics ) Biologics are too complex to create an identical copy, but a similar copy can be created, which is called a biosimilar product Image source: AbbVie Inc

How are Biologics Made? It s complex! Final Molecular Structure is Unique to Manufacturing Process Variations between batches of the same drug from the same plant Adapted from: Kozlowski, S. Biosimilars An update focused on quality considerations. Office of Biotechnology Products. FDA; 2012.

What Are Biosimilars?

Biosimilars Biosimilars are a similar copy of an originator biologic therapy. The originator is also sometimes called the reference product or innovator. What should be the same? What is different? Strength Route of administration Effectiveness Safety profile They are NOT an identical copy in every way (glycosylation may differ)

Thousands of participants for disease indications such as: Rheumatoid arthritis, Crohn s, ulcerative colitis Originator Biologics Biologic developed and tested FDA Application Clinical Trials Biosimilars Biologic developed and tested FDA Application Clinical Trials Clinical trials on one or more disease indication(s) from originator Example: Rheumatoid arthritis Must demonstrate safety and effectiveness FDA and Drug Sponsor Review Meeting Biologic License Application FDA and Drug Sponsor Review Meeting Biosimilar Biologics License Application Must demonstrate high similarity to reference drug. No clinically meaningful differences Example: Approval for IBD, RA, AS Drug Approval and Labeling Drug Approval and Labeling Example: Approval for IBD, RA, AS

Biosimilars Can be Extrapolated to Other Indications Comparison studies of a biosimilar that show equivalent efficacy and safety to the originator in ONE INDICATION may be EXTRAPOLATED to all indications for the originator using analytical studies EXAMPLE: biosimilar infliximab that works equally well in rheumatoid arthritis can be extrapolated and receive FDA approval without additional clinical trials for Crohn s disease, ulcerative colitis, ankylosing spondylitis, psoriasis and psoriatic arthritis. Indication 6 Indication 6 Indication 1 Indication 4 Indication 2 Indication 3 Mechanism of action Pharmacokinetics Immunogenicity Toxicities Adapted from: US Biologics Price Competition and Innovation Act of 2009

Interchangeable Biosimilars Interchangeable designation of biosimilars may allow for free exchange with originator biologics with no greater risk of adverse effects or diminished efficacy Statute allows pharmacy substitution of interchangeable biosimilars without prescriber intervention Subject to each state s laws and regulations governing drug FDA determines whether a biosimilar is interchangeable or not Requires studies of cross-over between originator and biosimilar Adapted from: US Biologics Price Competition and Innovation Act of 2009

State variations on: Prescriber notification Patient notification Medically Necessary Pharmacy records www.ncsl.org, accessed October 24 th, 2016

<<CALIFORNIA>> In order for substitution to take place... The biosimilar must be approved as interchangeable by the FDA The prescriber did not personally indicate that a substitution was NOT to be made The pharmacist must make an electronically accessible entry in a patient record system of the specified biosimilar product provided Pharmacist provides alternative record method http://www.ncsl.org/research/health/state-laws-and-legislationrelated-to-biologic-medications-and-substitution-ofbiosimilars.aspx#2013-14, accessed, 6.14.16

What Is In The Pipeline?

Biosimilar for IBD Inflectra TM is the first FDA approved biosimilar for inflammatory bowel disease Has biosimilarity to Infliximab (Remicade ) Studied in: Ankylosing Spondilitis Rheumatoid Arthritis Extrapolated to: Crohn s disease (in adults and children) Ulcerative colitis (in adults) Not interchangeable Available December, 2016 Amjevita TM Has biosimilarity to Adalimumab (Humira ) Studied in: Plaque psoriasis Rheumatoid Arthritis Extrapolated to: Crohn s disease and ulcerative colitis (in adults) Not interchangeable Source: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm494227.htm accessed May, 2016

Biosimilars in Development Over 650 biosimilars in development 1 Nearly 50% of biosimilars are in preclinical trial stage 1 It takes 7 to 8 years to develop a biosimilar, at a cost of between $100 million and $250 million 2 Product or Product Class Humira (adalimumab) Remicade (infliximab) Biosimilars 13 9 1 Radar RA. Bioproc Int. 2013; 11(6): S16-23. 2 Blackstone EA, et al. Am Health Drug Benefits. 2013;6(8):469-478.

What Are The Issues? Transitioning?

Issues with Biosimilars Risk of having the originator therapy in patient transition to a non-interchangeable biosimilar in stable patient unknown Potential for immunogenicity or cross-reactivity Means that anti-drug antibodies will cross react Loss of response or allergic reaction to the originator will occur equally with the biosimilar Patients and physicians may confuse names and branding like: Remicade Originator VS Remsima Biosimilar In Europe Biosimilar labels will indicate that it is a biosimilar and whether or not it is interchangeable with the originator

CCFA Position Statement on Biosimilars Safety and Effectiveness: Human testing Interchangeability Immunogenicity and cross reactivity Unique name/ identifier Undergo thorough human testing and meet highest safety standards Provide reasonable proof that transitioning would not incur immunogenicity or loss of response to innovator (vice versa) Risk of cross reactivity of anti-drug antibodies from innovator agent to biosimilar must be clearly understood, defined and listed on the label and prescribing information Each biosimilar should have unique identification number, name or else use international non-proprietary name standards to eliminate patient and provider confusion. http://www.ccfa.org/assets/pdfs/advocacy/biosimilar-position-statement.pdf. Accessed December 8, 2015.

CCFA Position Statement on Biosimilars Shared-Decision Making and Transparency: Notification to Prescribing Provider Prevention of Substitution The prescribing provider should be notified of the substitution of the innovator agent with a biosimilar (or vice versa). The prescriber should be able to prevent substitution by indicating dispense as written or brand medically necessary. http://www.ccfa.org/assets/pdfs/advocacy/biosimilar-position-statement.pdf. Accessed December 8, 2015.

Be an Informed Advocate It is important to be informed and advocate for your care. Understand your insurance Be knowledgeable about state laws regarding biosimilars Proactively discuss your treatment with provider Get engaged, become a CCFA advocate Resources: o online.ccfa.org/brochures o www.fda.gov o www.ccfa.org Get Involved: Become an Advocate

Contributors Noa Krugliak Cleveland, MD Resident Physician University of Chicago Medicine Government & Industry Affairs Committee, CCFA Faculty David T. Rubin, MD Professor of Medicine Chief, Section of Gastroenterology, Hepatology and Nutrition University of Chicago Medicine Chair, Government & Industry Affairs Committee, CCFA CCFA Staff Laura D. Wingate Vice President Patient & Professional Services Catherine Soto, MPA National Education Manager 2016 Crohn s & Colitis Foundation of America

Questions?

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