Important Facts. Health Care Professionals Should Know About Biosimilars

Transcription

1 Important Facts Health Care Professionals Should Know About Biosimilars

2 Biosimilars: Defining Characteristics Biosimilars are highly similar versions of reference biologics, with no clinically meaningful differences in terms of safety, purity, and potency. 1 Biologics, including biosimilars, are much more complex than small molecules 2-5 Small molecule drug Small biologic Large biologic COMPLEXITY While small molecule generics are chemically synthesized, biosimilars (and reference biologics) are created in living cells and require significant expertise and state-of-the-art technology. 2,4 Development of Biosimilars Extensive analytical, nonclinical, and clinical studies are part of development 1 The goal of biosimilar development is to demonstrate that there are no clinically meaningful differences between the proposed biosimilar and the reference biologic based on the totality of evidence. 1,6-8 Standard Biologics Developmental Pathways Biosimilars Clinical studies Clinical pharmacology PK/PD clinical studies Bioequivalence in healthy volunteers clinical pharmacology PK/PD Confirm safety profile and efficacy in a disease population (dose ranging not necessary) Nonclinical Small Molecule Generics Nonclinical PK, pharmacokinetics; PD, pharmacodynamics. Biosimilar development does not independently reestablish the clinical benefit of the reference biologic. 1

3 Potential of Biosimilars Projected growth in prescription drug spending creates a need for efficiencies within health care systems 9,10 As possible alternatives to existing biologics, biosimilars have the opportunity to address growing market demands and potentially expand access for patients with life-threatening and chronic diseases : Biologics accounted for nearly half of approximately $85 billion spent on the top 15 drugs in of 15 highest expenditure drugs were biologics, accounting for $39.5 billion in spending in Globally, biologic sales continue to grow as a proportion of total pharmaceutical sales including small molecules 15 Biosimilars may offer a number of potential benefits to patients, payers, and providers in addition to cost savings to the health care systems Offer a variety of therapeutic options Possible savings and efficiencies to the health care system Potential of biosimilars for patients, payers, and providers Additional treatment choices at a lower cost to the health care system Increase access to biologics, which may lead to improved health outcomes overall

4 Regulatory Pathway for Biosimilars Standard and abbreviated pathways for drug approval in the United States 1,8,16-20 Biosimilars may be approved through an abbreviated licensure pathway if similarity with a reference biologic has been established. 1 Small molecules Approved via Food, Drug, and Cosmetic Act (FDCA) Generics Biologics Approved via Public Health Service Act (PHSA) Biosimilars New drug application (NDA) Abbreviated new drug application (ANDA), Hatch-Waxman Biologics license application (BLA) Biosimilar biologics license application (BPCI Act) Benefit/risk profile and efficacy must be demonstrated Bioequivalence must be demonstrated Benefit/risk profile and efficacy must be demonstrated Must demonstrate high similarity to reference/no clinically meaningful differences Higher standards to obtain interchangeable designation The development of biosimilars involves substantial investment of time and resources 21 A biosimilar may take up to 9 years and cost up to $135 million to develop, whereas development of a small molecule generic may take 2 years and cost $1-$4 million Although the FDA has indicated that interchangeability is possible, it has not provided detailed guidance on approval requirements. 1 Interchangeability of a Biosimilar and a Reference Biologic Biosimilarity must be established before designation of interchangeability. The risk, in terms of safety profile or diminished efficacy, of alternating or switching between the biosimilar and the reference biologic must not be greater than the risk of using the reference biologic without such alternation or switch. 20

5 Extrapolated Indications Are Not Automatic Data collected for approval of a biosimilar in 1 indication may be extrapolated to 1 or more indications originally approved for the reference biologic. 1,25 An extrapolated indication has not been directly studied in a comparative clinical trial with a reference biologic 6 clinical data from the studied indication may help support extrapolation to other indications 1 Biosimilars Pathway clinical studies clinical pharmacology PK/PD Nonclinical Convincing scientific justification to support extrapolation to the approved indication(s) of a reference biologic Extrapolated indications Image adapted from Sherman RE. Biosimilar biological products [biosimilar guidance webinar]. February 15, Key aspects that may be considered for extrapolation 1 : Mechanism of action in each condition Pharmacokinetics and biodistribution Expected toxicities Other factors such as patient comorbidities and concomitant medications Substitution of a Biosimilar for a Reference Biologic Several states have enacted legislation on biologics and biosimilar substitution that may typically include the following 27,28 : Substitution is permitted only if the biosimilar has been designated as interchangeable Substitution may be prohibited if the prescriber has indicated a preference for the reference biologic The prescriber must be notified of any substitution made by the pharmacy

6 References: 1. US Food and Drug Administration. Guidance for Industry: Scientific Considerations in Demonstrating Biosimilarity to a Reference Product. Silver Spring, MD: FDA; Mellstedt H, Niederwieser D, Ludwig H. The challenge of biosimilars. Ann Oncol. 2008;19(3): Kozlowski S, Woodcock J, Midthun K, Sherman RB. Developing the nation s biosimilars program. N Engl J Med. 2011;365(5): Huml RA, Chance K, Baum AR, Provost E. Investment decisions based on biosimilar programs, part 1. Regulatory Affairs Professionals Society; August Accessed July 20, National Center for Biotechnology Information. Structure Summary MMDB. Human growth hormone. Structure/mmdb/mmdbsrv.cgi?uid= Accessed November 9, Bui LA, Taylor C. Developing clinical trials for biosimilars. Semin Oncol. 2014;41(suppl 1):S15-S Kingham R, Klasa G, Carver KH. Key regulatory guidelines for the development of biologics in the United States and Europe. In: Wang W, Singh M, eds. Biological Drug Products: Development and Strategies. Hoboken, NJ: John Wiley & Sons. 2014: US Food and Drug Administration. Abbreviated New Drug Applications (ANDA): Generics. Updated August 4, AbbreviatedNewDrugApplicationANDAGenerics/. Accessed August 25, Centers for Medicare & Medicaid Services. National Health Expenditure Projections Reports/ NationalHealthExpendData/NationalHealthAccountsProjected.html. Last updated: July 30, Accessed April 21, IMS Institute for Healthcare Informatics. Delivering on the Potential of Biosimilar Medicines: The Role of Functioning Competitive Markets. Parsippany, NJ: IMS Institute for Healthcare Informatics; March Henry D, Taylor C. Pharmacoeconomics of cancer therapies: considerations with the introduction of biosimilars. Semin Oncol. 2014;41(suppl 3):S13-S Strober BE, Armour K, Romiti R, et al. Biopharmaceuticals and biosimilars in psoriasis: what the dermatologist needs to know. J Am Acad Dermatol. 2012;66(2): Scheinberg MA, Kay J. The advent of biosimilar therapies in rheumatology O brave new world. Nat Rev Rheumatol. 2012;8(7): IMS Institute for Healthcare Informatics. Medicines Use and Spending in the U.S.: A Review of 2015 and Outlook to Parsippany, NJ: IMS Institute for Healthcare Informatics; April EvaluatePharma. World Preview 2015, Outlook to th Edition; June Accessed October 13, US Food and Drug Administration. New Drug Application (NDA). Updated March 29, HowDrugsareDevelopedandApproved/ApprovalApplications/NewDrugApplicationNDA/. Accessed October 6, US Congress. Drug Price Competition and Patent Term Restoration Act of 1984, Title I, 98 Stat 1585 Public Law US Congress. Biologics Price Competition and Innovation Act of 2009, Title VII, Subtitle A, of the Patient Protection and Affordable Care Act, Public Law , 124 Stat. 119, US Congress. United States Public Health Service Act, Sec. 262 Regulation of Biological Products. 42USC Accessed October 6, US Food and Drug Administration. Guidance for Industry: Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of Silver Spring, MD: FDA; Blackstone EA, Fuhr JP. The economics of biosimilars. Am Health Drug Benefits. 2013;6(8): Development of biosimilars. GaBI Online. January 7, Accessed September 28, Grabowski H, Cockburn I, Long G. The market for follow-on biologics: how will it evolve? Health Affairs. 2006;25(5): IMS Health. Shaping the Biosimilars Opportunity: A Global Perspective on the Evolving Biosimilars Landscape. London, UK: IMS Health Incorporated; December European Medicines Agency. Concept Paper on Extrapolation of Efficacy and Safety Profile in Medicine Development [final]. London, UK: EMA; March 19, EMA/129698/ Sherman RE. Biosimilar biological products [biosimilar guidance webinar]. February 15, HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/ucm pdf. Accessed January 4, National Conference of State Legislatures. State Laws and Legislation Related to Biologic Medications and Substitution of Biosimilars. Accessed September 16, Benedict AL. State-level legislation on follow-on biologic substitution. J Law Biosci. 2014;1(2): Visit PfizerBiosimilars.com to learn more about biosimilars. PP-BIO-USA Pfizer Inc. All rights reserved. Printed in USA/November 2016