Presentation on theme: "Biosimilars in Canada: A Perspective from Innovative Industry Karen A. Burke, Ph.D. Director, Regulatory Affairs and Safety Amgen Canada Montreal Forum."— Presentation transcript:
Biosimilars in Canada: A Perspective from Innovative Industry Karen A. Burke, Ph.D. Director, Regulatory Affairs and Safety Amgen Canada Montreal Forum Pharmaceutical Discussions May 28, 2010
The comments provided here are solely those of the presenter and are not necessarily reflective of the positions, policies and practices of Amgen Inc. Disclaimer
Sensipar ® (chemical drug) Small molecular size (weight = 393) Enbrel ® (protein) Immense molecular size (weight = 150,000) Biologic versus “Small Molecule” Larger molecular size and weight than “small molecules” (traditional pharmaceuticals) Derived from living organisms Each cell line is unique Difficult to produce and replicate
What is an SEB / Biosimilar? An SEB is biologic drug that enters the market subsequent to a version previously authorized in Canada, and with demonstrated similarity to a reference biologic drug.
Images of EPO alfa purported to be “the same”, made throughout the world. When is “The Same” Not the Same?
Typical Protein Production Process Probably same gene sequence START Different vectorDifferent host cell Different fermentation/culture conditions Different downstream processing Typical Protein Production Process Different manufacturers will have different processes END Will result in different biophysical characteristics
Unwanted Immunogenicity Induce antibodies Proteins Patients Alter Pharmaco- kinetics Cross-react with native protein and induce adverse reactions e.g., EPO No effect Neutralise biological effects and compromise further therapy e.g., Factor VIII, GM-CSF
What’s In A Name? Follow-on Biologics (FOB) Similar Biotherapeuti c Products (SBP) Subsequent Entry Biologics (SEB) Follow-on Protein Products (FOPP) Biosimilars
2002 20032004200520062007200820092010201120122013 Legislative Regulatory Framework Regulatory Framework Commercial Regulatory Framework Regulatory Framework Commercial Regulatory Framework Regulatory Framework Legislative? Commercial Biosimilars/SEBs have been in Europe for the past few years Legislative
European Medicines Agency scientific guidelines for biosimilars 1 Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Quality Issues Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Nonclinical & Clinical Issues TITLEMAIN MESSAGES Recombinant Human Erythropoietin Recombinant Human G-CSF Recombinant Human Insulin Recombinant Human Growth Hormone Similar, but not identical Justify any differences Greater differences require more clinical data Equivalent efficacy Similar safety (not worse) Similar immunogenic potential Generic standards do not apply Actual non-clinical and clinical requirements Study designs, post-marketing commitments etc. 1 http://www.emea.europa.eu/htms/human/humanguidelines/multidiscipline.htmhttp://www.emea.europa.eu/htms/human/humanguidelines/multidiscipline.htm
Clinical Testing is needed to determine efficacy and patient safety 57% of patients developed antibodies to Omnitrope in the first study Problem was residual host-cell protein Re-developed purification process Conducted a second phase 3 study –Antibody levels reduced Omnitrope (somatropin) 2 Reference product: Genotropin (Pfizer) Lower quality –Not as pure as Roferon-A Lower efficacy than Roferon-A –More patients relapsed Safety profile worse than Roferon-A –More side-effects Alpheon (interferon alfa-2a) 3 Reference product: Roferon-A (Roche) APPROVED REJECTED European Medicines Agency Review Practical experience from Europe informs the SEB discussion elsewhere 2. http://www.emea.europa.eu/humandocs/Humans/EPAR/omnitrope/omnitrope.htmhttp://www.emea.europa.eu/humandocs/Humans/EPAR/omnitrope/omnitrope.htm 3. http://www.emea.europa.eu/humandocs/PDFs/EPAR/alpheon/H-585-RAR-en.pdfhttp://www.emea.europa.eu/humandocs/PDFs/EPAR/alpheon/H-585-RAR-en.pdf
Substitution EU states are preventing automatic substitution http://www.emea.europa.eu/pdfs/human/pcwp/7456206en.pdf Substitution by pharmacist without physician consent has been rejected by more than half of the EU member states – including France, Germany, UK, Italy and Spain
President Obama speech to American Medical Association – June 2009 On Health Care Reform: “…we need to introduce generic biologic drugs into the marketplace. These are drugs used to treat illnesses like anemia. But right now, there is no pathway at the FDA for approving generic versions of these drugs.”
US healthcare reform legislation passed March 2010 21 Some requirements specified in text of legislation: Information showing same mechanism of action for proposed condition(s) of use (to the extent MOA is known for reference product) Information showing same dosage form, strength, and route of administration Next, the FDA will determine how to bring this new pathway to implementation. One aspect was a pathway for biosimilar approvals
2002 20032004200520062007200820092010201120122013 Legislative Regulatory Framework Regulatory Framework Commercial Regulatory Framework Regulatory Framework Commercial Regulatory Framework Regulatory Framework Legislative? Commercial Canada is unique in establishing a regulatory framework without new biosimilar-specific legislation or regulations April 22, 2009 Health Canada approves the first biosimilar in Canada: Sandoz’ Omnitrope (somatropin) Legislative
Health Canada’s Development of a Regulatory Approval Pathway for SEBs –Open consultation –Stakeholder comments appear to be taken into consideration –Final guidance appears science-based, with attention to patient safety Clearly, application and implementation will be key 2005 2006 2007 2008 2009 2010 “Fact Sheet” issued Draft guidance issued for comment Final Guidance Issued Face-to-Face Consultation Numerous opportunities for dialogue Written comments always welcomed Numerous opportunities for dialogue Written comments always welcomed 2 nd draft issued for comment
Post-approval studies are a fundamental basis of biosimilar approval Repeated changes would confound data Physicians may specifically choose one biologic over another Different biologics may have different labels e.g. EU Sandoz EPO has no sc use in renal anemia Theoretical potential for systematic lowering of immune tolerance Subtle potency or safety differences may have clinical consequences 11 ESAs in EU Repeated changes would confound long- term safety data Repeated or undocumented changes could compromise traceability Reliable data for post- approval studies Physician opinion or Different approved clinical use Uncertain clinical consequences of repeated switching Accurate and Clear Pharmacovigilance “It is noteworthy that once approved, an SEB, like any new drug, cannot be substituted or used interchangeably with the reference product used in the studies.” Health Canada letter to BIOTECanada, June 23, 2009 123 4 Considerations Moving Forward How to ensure this is understood by ALL participants in the healthcare system?
Europe is Tackling the “Traceability” Challenge of ESAs after the Fact Eprex ® (epoetin alfa) NeoRecormon ® (epoetin beta) Aranesp ® (darbepoetin alfa) Eprex ® (epoetin alfa) NeoRecormon ® (epoetin beta) Eprex ® (epoetin alfa) NeoRecormon ® (epoetin beta) Aranesp ® (darbepoetin alfa) Dynepo ® (epoetin delta) Mircera ® (peg-epoetin beta) Ratioepo ® (epoetin theta) Biopoin ® (epoetin theta) –Binocrit ® (epoetin alfa) –Abseamed ® (epoetin alfa) –Epoetin alfa Hexal (epoetin alfa) –Silapo ® (epoetin zeta) –Retacrit ® (epoetin zeta) Can our current systems in Canada manage this? = Full MAA* –= Biosimilar MAA 1998 2001 2009 Three levels of information are needed for biologics and biosimilars to allow health authorities and manufacturers to trace an event to its root cause: Drug class Individual manufacturer’s product – distinct name Manufacturer’s lot number * Marketing Authorization Application
A Possible Solution – Australian approach A distinct name was assigned – clearly differentiating from epoetin alfa This would be highly useful to overcome pharmacovigilance challenges
Though some concerns remain, Canada’s SEB regulatory environment is evolving well Further considerations should include –education of stakeholders on criticality of knowing what was prescribed and what was dispensed –distinct naming (INNs) Our approach should be always be supported by science In Conclusion Patient safety must always remain the highest priority