Clinical Trial Strategies in Biosimilar Drug Development

  • ID: 4421384
  • Report
  • 149 pages
  • Datamonitor Healthcare
1 of 3
As the patent cliff for many blockbuster biologic therapies is approaching, clinical development programs for biosimilar options to those therapies are emerging at a rapid pace. Among the key areas of development is biologics in the autoimmune/inflammation, oncology, and endocrinology/nephrology space. Sponsors of biosimilar projects are carefully designing their trials, assessing the most suitable target populations, and geography.

The concept of interchangeability in the US, where a reference product and a biosimilar are considered freely interchangeable, is not seen in Europe or other developed regions. By gaining an interchangeability status, a biosimilar may greatly enhance its uptake, however the FDA requires that the applicant should strictly adhere to the recently issued Guidelines on Interchangeability. The guideline asks sponsors to conduct a tailored clinical investigation containing multiple elements of switching between the brand and biosimilar as a proof that switching is a safe practice. This report outlines the approaches to switching that various sponsors have adopted prior to the availability of the FDA guidance, and after its publication.
Note: Product cover images may vary from those shown
2 of 3
1 EXECUTIVE SUMMARY
  • The volume of biosimilar clinical trials initiated globally is growing
  • Autoimmune/inflammation is the top targeted area for biosimilar development
  • Oncology biosimilars come as a second choice for biosimilar developers
  • Biosimilars in endocrinology/nephrology are progressing through the pipeline
  • Some biosimilar sponsors also target therapy areas such as ophthalmology, reproductive health, and multiple sclerosis
  • Biosimilar sponsors may employ switching designs in their Phase III trials to demonstrate interchangeability
2 OVERVIEW OF CLINICAL TRIAL STRATEGIES
  • Biosimilar development is associated with many risks, but potential high returns
  • Comparison of biosimilar approval pathways
  • Views on indication extrapolation differ among regulatory authorities
  • The FDA outlined requirements for biosimilar sponsors seeking interchangeability status
  • Bibliography
3 GLOBAL TRENDS IN BIOSIMILAR CLINICAL TRIALS
  • The total number of clinical trials for biosimilar candidates has been incrementally increasing
  • The growth in biosimilar clinical trial volume is driven by the expiration of branded drug patents
  • A higher proportion of bioisimilar development projects is targeted towards regulated markets
  • A diverse range of industry sponsors are involved in biosimilar clinical development
  • Biosimilar sponsors carefully choose trial location regions
  • The top three therapy areas for the development of biosimilars are autoimmune and inflammation, oncology, and endocrinology/nephrology
  • Biosimilar sponsors carefully choose which disease indications to study in clinical trials
  • Bibliography
4 AUTOIMMUNE/INFLAMMATION BIOSIMILAR TRIAL TRENDS
  • Autoimmune/inflammation is the therapeutic area most often targeted by biosimilar developers
  • The most often targeted molecules in regulated markets are anti-TNF therapies
  • Biosimilar sponsors initiating trials in A/I indications are joining a highly competitive space
  • Analysis of tested A/I indications for biosimilars
  • Europe is the most active clinical trial hub for A/I biosimilar clinical development
  • Bibliography
5 ONCOLOGY BIOSIMILAR TRIAL TRENDS
  • Oncology is the second most often targeted therapeutic area by biosimilar developers
  • Sponsors developing biosimilars in oncology are targeting three blockbuster MAbs
  • Analysis of biosimilar sponsors conducting clinical trials in oncology indications
  • Choosing an appropriate target population for oncology biosimilar trials is essential
  • Europe has the highest number of clinical trial sites for oncology biosimilars
  • Bibliography
6 ENDOCRINOLOGY/NEPHROLOGY BIOSIMILAR TRIAL TRENDS
  • Endocrinology/nephrology is the third most often targeted therapeutic area by biosimilar developers
  • Insulin products and erythropoetin stimulating agents are among the top reference choices for developers of biosimilars in endocrinology/nephrology
  • Analysis of biosimilar sponsors conducting clinical trials in endocrinology/nephrology indications
  • The US is the most active region chosen for the clinical development of endocrinology/nephrology biosimilars
  • Bibliography
7 BIOSIMILAR TRIAL TRENDS IN OTHER THERAPEUTIC AREAS
  • A key biosimilar target in ophthalmology is the monoclonal antibody ranibizumab
  • A key biosimilar target in reproductive health is follitropin alfa
  • Biosimilar sponsors also develop biosimilars in hematology, hepatitis C, and multiple sclerosis
  • Bibliography
8 PHASE III SWITCHING STUDY DESIGNS AND BIOSIMILAR INTERCHANGEABILITY
  • There is a need for data from switching studies
  • The FDA has issued draft interchangeability guidelines to shed some light on the issue of interchangeability
  • Biosimilar sponsors may conduct switching studies to assess safety and effectiveness of switching between the brand and
  • biosimilar
  • Bibliography
9 APPENDIX
  • Scope
  • Methodology
List of Figures
Figure 1: Clinical trial volume over time, per trial phase, 2011-17
Figure 2: Volume of biosimilar clinical trial starts by geographic market type, all therapeutic areas, 2011-17
Figure 3: Volume of biosimilar trials per wave in all regions, 2011-17
Figure 4: Volume of biosimilar trials per wave, in regulated markets and ROW, 2011-17
Figure 5: Biosimilar clinical trial starts, all therapeutic areas, 2011-17, by trial phase
Figure 6: Clinical trials in the regulated markets and in ROW regions: top 10 sponsors by total number, 2011-17
Figure 7: Volume of biosimilar clinical trials by sponsor and phase: top 15 sponsors, all regions, 2011-17
Figure 8: Volume of biosimilar clinical trials in the regulated markets and ROW, by country
Figure 9: Biosimilar clinical trial location by sponsor in the regulated markets: top 15 sponsors, by trial volume
Figure 10: Biosimilar clinical trial location by sponsor in ROW: top 15 sponsors, by trial volume
Figure 11: Volume of biosimilar clinical trials, by therapeutic area
Figure 12: Volume of clinical trial starts by therapeutic area in the regulated markets and ROW
Figure 13: Proportion of clinical trial volume within a specific therapeutic area, regulated markets, 2011-17
Figure 14: Overall biosimilar clinical trial volume by choice of reference product (top 10 products)
Figure 15: Volume of clinical trials targeting a specific disease indication: top 10 indications
Figure 16: Volume of Phase I and Phase III biosimilar clinical trials targeting a specific disease indication, regardless of region: top 5 indications per phase
Figure 17: Volume of Phase IV biosimilar clinical trials targeting a specific disease indication, regardless of region: top 10 indications
Figure 18: Volume of biosimilar clinical trial starts by geographic market type, A/I indications, 2011-17
Figure 19: Volume of biosimilar clinical trial starts by geographic market type, A/I indications
Figure 20: Choice of reference product for A/I biosimilar clinical trials, all regions and phases
Figure 21: Number of biosimilar trials in A/I indications, per reference product and phase
Figure 22: Clinical trial volume of biosimilar programs in A/I diseases, by start year, 2011-17
Figure 23: Top biosimilar sponsors in A/I indications, per phase
Figure 24: Map of the pipeline progress of the top 10 biosimilar developers in the A/I space in the EU, US, and Japan
Figure 25: Volume of A/I clinical trial starts per sponsor, per reference molecule: top sponsors
Figure 26: Status and sponsors of multinational Phase III A/I biosimilars programs
Figure 27: Volume of Phase III trials for biosimilars of each A/I reference product in the regulated markets
Figure 28: Status of Phase III A/I biosimilar trials for the top 10 sponsors in the regulated markets
Figure 29: Disease indications for Phase III trials of A/I biosimilars in the regulated markets, by reference product an sponsor
Figure 30: Indications studied in post-marketing trials of infliximab biosimilars for the regulated markets
Figure 31: Volume of biosimilar A/I clinical trial sites in the regulated markets and in ROW
Figure 32: Clinical trial locations for A/I biosimilar candidates per region
Figure 33: Volume of biosimilar clinical trial starts by geographic market type, oncology indications, 2011-17
Figure 34: Volume of biosimilar clinical trial starts by geographic market type, oncology indications
Figure 35: Choice of reference product for oncology biosimilar clinical trials, all regions and phases
Figure 36: Number of biosimilar trials in oncology indications, per reference product and phase
Figure 37: Clinical trial volume of biosimilar programs in oncology, by start year, 2011-17
Figure 38: Top biosimilar sponsors in oncology indications, per phase
Figure 39: Map of the pipeline progress of the top biosimilar developers in the oncology space in EU, US, and Japan: top four reference molecules
Figure 40: Volume of oncology clinical trial starts per sponsor, per reference molecule: top sponsors
Figure 41: Status and sponsors of oncology Phase III biosimilars programs targeting the regulated markets
Figure 42: Volume of Phase III trials for biosimilars of each oncology reference product in the regulated markets
Figure 43: Disease indications for Phase III trials of oncology biosimilars in the regulated markets, by reference product and sponsor
Figure 44: Volume of biosimilar oncology clinical trial sites in the regulated markets and in ROW
Figure 45: Clinical trial locations for oncology biosimilar candidates per region
Figure 46: Volume of biosimilar clinical trial starts by geographic market type, endocrinology/nephrology indications, 2011-17
Figure 47: Volume of biosimilar clinical trial starts by geographic market type, endocrinology/nephrology indications
Figure 48: Choice of reference product for endocrinology/nephrology biosimilar clinical trials, all regions and phases
Figure 49: Number of biosimilar trials in endocrinology/nephrology indications, per reference product and phase
Figure 50: Clinical trial volume of biosimilar programs in endocrinology/nephrology indications, by start year, 2011-17
Figure 51: Top biosimilar sponsors in endocrinology/nephrology indications, per phase
Figure 52: Map of the pipeline progress of the top biosimilar developers in the endocrinology/nephrology space in the EU, US or Japan
Figure 53: Volume of endocrinology/nephrology clinical trial starts per sponsor, per reference molecule (top sponsors)
Figure 54: Volume of biosimilar endocrinology/nephrology clinical trial sites in the regulated markets and in ROW
Figure 55: Volume of biosimilar Phase III trials in A/I which have or do not have a switching component
Figure 56: Detailed outline of different types of switching designs used by sponsors in Phase III trials of A/I biosimilar products
Figure 57: Volume of clinical trials per switching design (A/I biosimilars)
Figure 58: Presence of switch elements in adalimumab biosimilar Phase III trials in regulated markets
Figure 59: Indications studied in adalimumab Phase III trials
Figure 60: Volume of switching trials per switch type, Phase III adalimumab biosimilar trials
Figure 61: Presence of switch elements in etanercept biosimilar Phase III trials in regulated markets
Figure 62: Indications studied in etanercept Phase III trials
Figure 63: Volume of switching trials per switch type, Phase III etanercept biosimilar trials
Figure 64: Presence of switch elements in infliximab biosimilar Phase III trials in regulated markets
Figure 65: Indications studied in infliximab Phase III trials
Figure 66: Volume of switching trials per switch type, Phase III infliximab biosimilar trials
Figure 67: Presence of switch elements in rituximab biosimilar Phase III trials in regulated markets
Figure 68: Indications studied in rituximab Phase III trials
Figure 69: Volume of switching trials per switch type, Phase III rituximab biosimilar trials

List of Tables
Table 1: Comparison of biosimilar approval pathways
Table 2: Indications in which Remicade and infliximab biosimilars have obtained approval in from the regulatory authorities in EU, US and Canada
Table 3: Indications in which Enbrel and etanercept biosimilars have obtained approval in from the regulatory authorities in EU, US and Canada
Table 4: Indications in which Rituxan/MabThera and rituximab biosimilars have obtained approval in from the regulatory authorities in EU, US and Canada
Table 5: Overview of FDA interchangeability guidelines
Table 6: Waves of biosimilar development
Table 7: Number of Phase I trials conducted by sponsors in the regulated regions, per indication studied
Table 8: Number of Phase III trials conducted by sponsors in the regulated regions, per indication studied
Table 9: Number of Phase I trials conducted by sponsors in the regulated regions, per indication studied
Table 10: Phase III trials of biosimilar trastuzumab in metastatic or early HER2-positive breast cancer patients
Table 11: Competitive landscape of biosimilar ranibizumab, 2011-17
Table 12: Competitive landscape of biosimilar follitropin alfa, 2011-17
Table 13: Competitive landscape of clinical-stage biosimilars in hematology, 2011-17
Table 14: Competitive landscape of clinical-stage biosimilars of peginterferon alfa for the treatment of hepatitis, 2011-17
Table 15: Competitive landscape of clinical-stage biosimilars in multiple sclerosis, 2011-17
Table 16: Adalimumab biosimilar Phase III trials in regulated markets: trial design
Table 17: Etanercept biosimilar Phase III trials in regulated markets: trial design
Table 18: Infliximab biosimilar Phase III trials in regulated markets: trial design
Table 19: Rituximab biosimilar Phase III trials in regulated markets: trial design
Note: Product cover images may vary from those shown
3 of 3

Loading
LOADING...

4 of 3
Note: Product cover images may vary from those shown
Adroll
adroll