1. Biosimilars: Conversion, Switching, and Educating Prescribers and Patients
Philip Schwieterman PharmD, MHA
Director of Oncology and Pediatric Pharmacy
UK HealthCare Markey Cancer and KY Children’s Hospital
Lexington, Kentucky

2. Background Biosimilar (351(k)(4)):
“Highly similar” to reference product; approved via biosimilars pathway
Approved using abbreviated data for comparability
BCPIA requires manufacturer meet requirements for a biosimilar:
Licensing
Testing
Manufacturing
Safety
Exclusivity
Labeling
Describes biosimilar vs interchangeable products
Communication requirements between the two companies
Others
Currently 16 products approved, 7 available

4. Patient Conversion: Interchangeable
Interchangeable (351(k)):
the use of a biosimilar without impacting on safety or efficacy if it is alternated or switching between the biosimilar and the innovator compared to the use of the innovator without alternation or switching
A biosimilar that can be substituted for the reference without permission from prescriber
More extensive data package for comparability supporting that the interchangeable biosimilar anticipated to produce same clinical effects for all the reference product’s licensed conditions
No interchangeable products available
Very little conversion data available, especially for therapeutic products

5. Patient Conversion: Immunogenicity Concerns
the propensity of the therapeutic protein product to generate immune responses to itself
Consequences include neutralizing antibodies or cytokine release
Scientific tools for detecting immunogenicity exist, but they are not precise
Clinical consequences:
Loss or diminished efficacy or safety
Some rare but serious adverse reactions
Changes to the structure of the protein increase variation in immunogenicity
How does this vary per Lot or Batch?
Variations in manufacturing must be minimized
FDA. Guidance for industry: immunogenicity assessment for therapeutic protein products. August 2014.

6. Available on the US Market?
Reference Product
Manufacturer
Biosimilar
Available on the US Market?
Interchangeable
Adalimumab (Humira®)
AbbVie
Adalimumab-adbm (Cyltezo®)
Adalimumab-atto (AmjevitaTM)
Adalimumab-adaz (Hyrimoz) No
Boehringer Ingelheim
Amgen
Sandoz
Bevacizumab (Avastin®)
Genentech
Bevacizumab-awwb (MvasiTM)
Epoetin alfa
Epoetin alpha-epbx (Retacrit)
Yes
Pfizer
Etanercept (Enbrel®)
Amben
Etanercept-szzs (Erelzi®)
Filgrastim (Neupogen®)
Filgrastim-sndz (Zarxio®)
Filgrastim-aafi (Nivestym®)
Infliximab (Remicade®)
Jansenn
Infliximab-abda (RenflexisTM)
Infliximab-dyyb (Inflectra®)
Infliximab-qbtx (Ixifi®)
Merck
Pegfilgrastim (Neulasta and Onpro® kit)
Pegfilgrastim-cbqv (Udenyca®)
Pegfilgrastim-jmdb (Fulphila®)
Coherus
Mylan
Rituximab (Rituxan®)
Rituximab-abbs (Truxima®)
Celltrion
Trastuzumab (Herceptin®)
Genentech/Roche
Trastuzumab-dkst (Ogivri®)
Trastuzumab—pkrb (Herzuma®)
Mylan/Biocon

7. Educating Prescribers : Clinical Assesment of Infliximab
NOR-SWITCH
Primary endpoint was disease worsening during 52 week follow-up
482 patients enrolled and randomized
241 to Infliximab
241 to Biosimilar
Adverse events were 10% for infliximab, 9% for biosimilar
Disease worsening was 26% for infliximab, 30% for biosimilar
End conclusion is that biosimilar is non-inferior to reference product
Jorgensen, KK et all. Switching from originator biosimilar to CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomized, double-blind, non-inferiority trial. Lancet 2017 June 10; 389(10086):

8. Educating Providers: Filgrastim
Sensorgram overlay of the receptor binding affinities of biosimilar and originator filgrastim, based on a surface plasmon resonance-based interaction assay using Biacore technology. RU resonance units
Sorgel F, et al. BioDrugs. 2015;29:

9. Educating Providers: Filgrastim
Pharmacokinetic analysis: geometric mean filgrastim concentration–time profiles for biosimilar and US originator filgrastim
Sorgel F, et al. BioDrugs. 2015;29:

10. Educating Prescribers : Pegfilgrastim
Accessed January 2019

11. Educating Providers: Filgrastim
N = 218 pts with breast cancer receiving myelosuppressive chemotherapy
Filgrastim 5 µg/kg/day administered over 6 chemotherapy cycles
Conclusion: biosimilar filgrastim noninferior to originator filgrastim at improving ANC counts
Blackwell K, et al. Ann Oncol ;26:

12. Educating Providers: Trastuzumab
Rugo HS, et al. JAMA. 2017;317:37-47.

13. Educating Prescribers: Insurance
Payer requirements:
There are several brands of long-acting granulocyte colony stimulating factors (G-CSFs) on the market, including Neulasta (pegfilgrastim), Fulphila (pegfilgrastim-jmdb), and pegfilgrastim- cbqv (Udenyca).There is a lack of reliable evidence that any one brand of long-acting G-CSF is superior to other brands for medically necessary indications. Fulphila and Udenyca are the least cost brands of long-acting G-CSF to Aetna. Consequently, because the Neulasta brand of long-acting G-CSF is more costly than the least cost brands of long-acting G-CSF, and the least cost brands of long-acting G-CSF are at least as likely to produce equivalent therapeutic results, Neulasta will be considered medically necessary only if the member has a contraindication, intolerance or ineffective response to one of the least cost brands of long-acting G-CSF, Fulphila or Udenyca

14. Educating Prescribers : Cost Savings
US Health Care system
Estimated cost savings of 3% annually from now to 2026
Potential of $24-$150 billion in cost savings
Mulcahy AW, Hlavka JP, Case SR. Biosimilar cost savings in the United States: initial experience and future potential. Santa Monica, CA: RAND Corporation, Accessed November 30, 2017.

15. Educating Patients: General
What is the difference between receiving a reference product and a biosimilar product?
Patients and their physicians can expect that there will be no clinically meaningful differences between taking a reference product and a biosimilar when these products are used as intended. All reference products and biosimilar products meet FDA’s rigorous standards for approval for the indications (medical conditions) described in product labeling. Once a biosimilar has been approved by FDA, patients and health care providers can be assured of the safety and effectiveness of the biosimilar, just as they would for the reference product.

16. New initation vs. continuation? Therapeutic vs. Supportive?
What’s the preferred product by their health plan
Potentially cheaper copay
Accessed Jan 2019

17. Educating Patients: Financial

18. Biosimilar Utilization: Educating Prescribers and Patients
Philip Schwieterman PharmD, MHA
Director of Oncology and Pediatric Pharmacy
UK HealthCare Markey Cancer and KY Children’s Hospital
Lexington, Kentucky