Biosimilars 101: How similar are they?

Transcription

1 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 differences between generics and biosimilars Describe financial and operational implications for oncology practices 1

2 Review of Biologics Hospira. Accessed 4/1/2016. Small Molecules Examples: Aspirin Warfarin Gabapentin Made through chemical reactions Easily reproduced Identical active ingredient Biologics Examples: Filgrastim Rituximab Cetuximab Made from a variety of natural sources Human, animal, or microorganism Complex (proprietary) manufacturing process Variability is unavoidable 2

3 Biologic Manufacturing D Haens, GR, et al. Journal of Crohn s and Colitis (2014) 8, Natural Protein Variation Significant variations in potency exist between lots FDA requires notification of any change in manufacturing Variations are not thought to produce clinically meaningful differences 3

4 Immunogenicity 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. Kahn FA. CRC Press, 2011;

5 Cost of Biologics 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 Péntek M, et al. Eur J Health Econ 2014; 15(suppl 1):S Express Scripts. scripts.com/lab/insights/industry updates/the $250 billion potential ofbiosimilars. Accessed 4/1/ biosimilars.com/en/biosimilars/why biologics matter en.shtml 5

6 Ventola, C. P&T. 2013; 38(5): What is a Biosimilar? 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. FDA. pprovalapplications/therapeuticbiologicapplications/biosimilars/. Accessed 4/1/

7 Biosimilars in the U.S. Biologics Price Competition and Innovation Act of 2009 (BPCI Act) Part of the Affordable Care Act Signed into law on March 23, st biosimilar filgrastim-sndz (Zarxio) approved in US on March 6, 2015 FDA Approval Process Christl, L. FDA. FDA.gov. Accessed April 7,

8 STRUCTURE McCamish M, Woollett G. Clin Pharm & Ther. 2012; 91(3); FUNCTION McCamish M, Woollett G. Clin Pharm & Ther. 2012; 91(3);

9 PK & PD McCamish M, Woollett G. Clin Pharm & Ther. 2012; 91(3); EFFICACY & SAFETY McCamish M, Woollett G. Clin Pharm & Ther. 2012; 91(3);

10 Quintiles. knowledge connect/regulatory requirements. Accessed 4/1/2016. Reference Product (Trade Name) Adalimumab (Humira) Manufacturer Biosimilar Manufacturer Abbvie Adalimumab adbm (Cyltezo) Boehringer Ingelheim Biosimilar s Availability on the U.S. Market Unavailable Adalimumab atto (Amjevita) Amgen Unavailable (delayed until 2023) Bevacizumab (Avastin) Etanercept (Enbrel) Filgrastim (Neupogen) Infliximab (Remicade) Genentech Bevacizumab awwb (Mvasi) Genentech Unavailable Amgen Etanercept szzs (Erelzi) Sandoz Unavailable Amgen Filgrastim sndz (Zarxio) Sandoz Available Janssen Infliximab abda (Renflexis) Merck Available Infliximab dyyb (Inflectra) Pfizer Available Infliximab qbtx (Ixifi) Pfizer Unavailable Trastuzumab (Herceptin) Genentech /Roche Trastuzumab dkst (Ogivri) Mylan / Biocon Unavailable 10

11 Other Biosimilar Concepts 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 11

12 2015 ASCO Policy Brief 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. Lyman, GH. ASCO changing cancer care landscape. Challenges to Biosimilars 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 12

13 Payment Pitfalls Reference product dispensed when biosimilar is preferred Biosimilar dispensed when reference product is preferred Biosimilar or reference product dispensed prior to obtaining authorization Authorization for one product obtained and the other is dispensed Medication Safety 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 13

14 On The Horizon 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 Chen Q. F1000Res. 2016; 5: F1000 Faculty Rev 912. Conclusions 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 14

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 of Biosimilar Products in the US. FDA. FDA.gov. Accessed April 7, D Haens GR, et al. Future directions in inflammatory bowel disease management. Journal of Crohn s and Colitis (2014) 8, 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. updates/the $250 billion potential of biosimilars. Accessed 4/1/2016. FDA. Information on biosimilars. ed/approvalapplications/therapeuticbiologicapplications/biosimilars/. Accessed 4/1/2016. Hospira. Biosimilars Compared to Generic Drugs. Accessed 4/1/

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): e Lyman, GH. Biosimilars in the Changing Cancer Care Landscape. ASCO changing cancer care landscape. McCamish M, Woollett G. The State of the Art in the Development of Biosimilars. Clin Pharm & Ther. 2012; 91(3); 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):S 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, Ventola C. Biosimilars Part 1: Proposed Regulatory Criteria for FDA Approval. P&T. 2013; 38(5):