Biosimilar

Biological agent facts

fastest growing segment of the pharmaceutical market -product pipeline -new indications -increasing utilization thousands of products in development

Pt protection and affordable care act

make drugs more affordable established comprehensive health insurance reforms includes the biologic price competition and innovation act

What is a biologic?

"any virus, therapeutic serum, toxin, antitoxin, or analogous protein applicable to the prevention, tx or cure of disease or injuries of man"

Biosimilar

-"highly similar" to the reference product -acknowledges there are minor differences in clinically inactive components -no clinically meaningful differences between the biological product and reference product in terms of: safety, purity, potency

Scientific considerations in demonstrating biosimilarity to a reference product

-FDA guidance to assist companies in demonstrating biosimilarity -totality of the evidence approach -FDA intends to determine the amount and type of data needed for biosimilar approval on a case by case basis

Quality considerations in demonstrating biosimilarity to a reference protein product

-addresses general scientific principles -FDA guidance for analytic factors --physicochemical characterization --biological characterization -type, nature and extent of difference should be described in detail -goal is to be able to demonstrate the proposed product is "highly similar"

Supreme court ruling - june, 2017

-allows biosimilar manufacturers to start advertising before indications determined by the FDA -affirms 12 year exclusivity period and fosters competition -unclear if it will lead to market confusion

Biologic price competition and innovation act (BPCIA) or 2009

-amends the public health service act to provide a pathway for biosimilar approval -authorizes the FDA to designate a biosimilar product as "comparable" or "interchangeable" -provides 12 years of exclusivity for original reference product goals of legislation -improve pt access to less costly alternatives -foster a competitive environment

What data does the FDA look at to assess interchangeability?

-analytical studies - is the product "highly similar"? -animal studies -clinical studies

Permissible differences

-different formulation or delivery system (as long as such changes do not result in "clinically meaningful" differences) -biosimilar may obtain approval for fewer than all routes of administration -biosimilar may obtain fewer indications than reference product

"totality of the evidence"

-evidence analytical, physiochemical and biological characterizations -comparison between reference and biosimilar product in regard to: structure, function, animal data, PK/PD data, clinical immunogenicity, efficacy and safety

Cost saving

-expected cost saving is a major driver of biosimilar interest -data ultimately needed by the FDA will also costs -R&D costs of biosimilars substantial -->discounts expected to be 15-35% (vs. up to 8-% for generic chemical drugs) -still large savings for larger insurers

Biologic product naming

-guidance document issued by the FDA in January 2017 -->nonproprietary name -->non-binding (guidance only) -intended to identify specific products for -->billing -->claims -->pharmacovigilance -distinguishing suffix -->intended to help avoid inadvertent substitution -->should be used for: ordering, prescribing, dispensing, records, pharmacovigilance -devoid of meaning -core name designated by USAN council

FDA Purple Book

-introduced september 2014 -lists licensed biological products -term of reference products exclusivity -includes whether a product is biosimilar or interchangeable

Pharmacovigilance

-monitoring the safety of medicines to detect, assess, understand and prevent adverse effects -typically done post-marketing -critical for tracking immunogenicity -sources of reporting: electronic health records, claims data, pharmacists - MedWatch reports

Bioequivalence

-no significant difference in the rate and extent to which the active ingredient is available at the site of action -same molar dose given under similar circumstances -basis for generic drug substitutability biosimilarity DOES NOT EQUAL bioequivalence

CO biosimilar legislation

-signed into april 2015 -allows pharmacists to substitute biosimilars when FDA has declared the drugs interchangeable -must notify prescriber of product and manufacturer

Interchangeable

-the biologic product is "biosimilar" to the reference product -same clinical result -safety and efficacy risks are not greater with the biosimilar product vs the reference product -by statute, interchangeable means substitution may occur without consent of the prescriber -but pharmacies will need to carefully track which product was used

Reference product

-the single biological entity licensed by the FDA -the product to which the biosimilar is being compared -but, variable references exist for basis of comparison

Examples of biological agents

-vaccines -therapeutic proteins -monoclonal antibodies

FDA draft guidance for biosimilars

3 guidance documents 1. scientific considerations in demonstrating biosimilarity to a reference product 2. quality considerations in demonstrating biosimilarity to a reference protein product 3. biosimilars: questions and answers regarding implementation of the biologics price competition and innovation act of 2009

Suffix Do's and Dont's

Suffix should be -unique and devoid of meaning -4 lowercase letters (at least 3 are distinct) -nonproprietary Suffix should not be: -false/misleading (i.e. infer safety or efficacy) -include abbreviations used in clinical practice -connote the name of the license holder

Biological agent development

biologic agent R&D costs (average): $1.2B Development time (average: 10-15 yrs Consumer cost (average): $34,550

drug development

chemical drug R&D costs (average): $500-800M Development time (average: 7-10 yrs Consumer cost (average): varies widely

Generic chemical entities

structure: identical analytics: able to determine drug and generic drug are identical manufacturing process: organic medicinal chemistry process

Biosimilars

structure: same aa sequence, slight difference in protein folding and glycosylation analytics: analytic technique to determine final structure not yet available manufacturing process: extremely complex