What do physicians expect from a new drug?

Transcription

1 What do physicians expect from a new drug? New drug Novel activity Efficacy Safety Affordable cost

2 Approval of new biologic drugs Is consistently increasing New Biotech Drug and Vaccine Approvals/ New Indication Approvals by Year from Biotechnology Industry Organization (2007)

3 Sales of new biologic drugs are consistently increasing

4 Biotechnology drug sales increased 5 fold in the last decade, expected to reach $100B this year Global biotech drug sales, $ bn

5 but this situation is changing 90% of biotechnology drugs will go off patent in the next 10 years 24 Large opportunity New affordable treatment options for more patients 17 All Biologics Patents expired 2009 or earlier Patents expiring Patents expiring Biosimilar opportunity Global biotech drug sales, $ bn, 2009

6 What do physicians expect from a biosimilar? New drug Novel activity Biosimilar Novel activity Efficacy Similar efficacy Safety Similar safety Affordable cost Lower cost

7 EMA description of biosimilar medicines Medicine which is similar to a biological medicine that has already been authorized (the biological reference medicine ) The active substance of a biosimilar medicine is similar to the one of the biological reference medicine Biosimilar and biological reference medicines are used in general at the same dose to treat the same disease

8 Key differences between how biosimilars and smallmolecule generics compare with the reference product Biosimilars Small-MoleculeGenerics Product Chemicalstructure Same amino acid Slight differences in terms of protein folding and glycosylation The active drug is chemically identical to the reference product Analyticalcharacterizat ion The final structure cannot be fully defined based on current analytical techniques; The degree of structural similarity to the reference product is unknown Current techniques are available to ensure that the active drug in the generic product is identical to the reference product Manufacturing Complexity Very complex Produced in living cells Involves several stages of purification, production, and validation of the final product Relatively simple, uses organic medicinal chemistry reactions Impact of a change in manufacturing process Small changes in process may alter the final structure and function of the protein Likely to be negligible because the end product is identical Regulation Legislation approving an abbreviated pathway The Biologics Price Competition and Innovation Act of 2009 establishes framework for an abbreviated approval pathway for biosimilars; guidance yet to be released by the FDA Hatch-Waxman Act allows generics to be approved through an Abbreviated New Drug Application (ANDA)

9 Why similar and not identical? Slight variations do not affect efficacy and safety as long as they are within well defined product specifications and the manufacturing process is well controlled Biotech drugs are complex / large molecules As a result Manufactured drugs may vary slightly* from the drug that was originally approved for example: batch to batch variation is often observed for any innovator s drug 9 10/2/2012 * In drug structure and physico chemical profile

10 EMA description of biosimilar medicines: Similarity is not identity! Since biosimilar and biological reference medicines are similar but not identical, the decision to treat a patient with a reference or a biosimilar medicine should be taken following the opinion of a qualified healthcare professional

11 EMEA/CHMP/BWP/49348/2005 Monoclonal Antibodies (draft concept paper)

12 Comparability exercise: a requirement of regulatory agencies An extensive physicochemical and biological comparability exercise is being performed in order to demonstrate the comparability between the Innovator and Biosimilar drug substance Additional preclinical, safety and efficacy demonstrations will be included in the comparability exercise as required on a product by product basis The comparability Exercise covers: Primary, secondary and tertiary structure Glycosylation profile and site Potency (CDC) Antigen recognition Disulphide bonds and free SH Aggregates and fragments Oxidised forms Pyroglutamination C-terminal clipping of heavy chain Deamidation

13 Biosimilar epoetins and filgrastim which received EMA approval Barosi et al, Haematologica 2011

14 Gascon P. Targ Oncol, 2012

15 3.12. Filgrastim biosimilars are now also a treatment option in Europe Recommendation grade A

16 3.11. Clinicians are encouraged to identify a product by brandname and ensure that no changes are made without informing both physician and patient