Biosimilarity must only be shown for 1 indication of the reference drug.1 Once the biosimilar is approved by the FDA, the agency may allow all indications of the reference drug to be extrapolated to the biosimilar without clinical data for these additional indications. There are some proposed exceptions to this rule, such as is the case with a reference product that has an orphan drug indication. A draft guidance document from the FDA states that if a reference product has orphan drug exclusivity for an indication, the biosimilar may not be licensed for the protected orphan indication “until after the expiration of the 7-year orphan drug exclusivity period or the 12-year reference product exclusivity period granted under section 351(k)(7) of the [Public Health Service] Act, whichever is later.”4

If a biosimilar is shown to be interchangeable with the reference drug, meaning that it meets additional standards to show that the biosimilar drug is expected to result in the same (rather than simply similar) clinical results as the reference drug, then the biosimilar can be substituted for the reference drug without the prescribing clinician or patient’s input.4 To date, none of the biosimilar products approved by the FDA have been granted an interchangeable designation.

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Approved biosimilars must following a nonproprietary naming convention initiated by the FDA that clearly indicates that the drug is a biosimilar, rather than the reference drug.5 The FDA assigns a suffix of four lowercase letters, which have no specific meaning. For example, the reference product trastuzumab currently has 5 FDA-approved biosimilar counterparts: trastuzumab-anns, trastuzumab-gyyp, trastuzumab-pkrb, trastuzumab-dttb, trastuzumab-dkst.6-10

Efficacy and Safety

If approved by the FDA, biosimilars are expected to perform in line with the reference drug because of the regulatory process that requires establishing the highly similar efficacy and safety of these products to their reference drug.1,5 In addition, a meta-analysis of the granulocyte colony-stimulating factors comparing filgrastim and epoetin alfa demonstrated that there were no significant differences in any outcome of efficacy or safety between any of the biosimilars and their reference drug.11 A meta-analysis comparing the efficacy of other biosimilars in oncology, specifically, has not yet been published.

Approval and Availability

Although the FDA has approved 23 biosimilars — and 9 of these are considered oncology medications (although there are some other biosimilars not technically classified as oncology therapies that can be used as supportive care in oncology) — many of these biosimilars are not yet available on the market, so they cannot be prescribed to patients.12 FDA approval means that the FDA allows the marketing of the biosimilar, but other steps must be taken before the biosimilar actually reaches the market. Reimbursement schemes must be established with the Centers for Medicare & Medicaid Services and private insurance companies.4 In addition, many manufacturers of reference drugs have filed intellectual property lawsuits against manufacturers of biosimilars, preventing the marketing of the biosimilars until the lawsuits are resolved or until the parties enter into a settlement agreement. A biosimilar manufacturer can choose to launch a product “at risk,” but that makes the biosimilar manufacturer vulnerable to patent litigation. Therefore, regulatory approval of a biosimilar in the US does not necessarily mean that the biosimilar is available for use in the clinic.

References

  1. Rugo HS, Rifkin RM, Declerck P, Bair AH, Morgan G. Demystifying biosimilars: development, regulation and clinical use. Future Oncol. 2019;15(7):777-790.
  2. Nabhan C, Parsad S, Mato AR, Feinberg BA. Biosimilars in oncology in the United States. a review. JAMA Oncol. 2018;4(2):241-247.
  3. de Mora F. Biosimilar: what it is not. Br J Clin Pharmacol. 2015;80(5):949-956.
  4. US Food and Drug Administration. Guidance for Industry: Reference Product Exclusivity for Biological Products Filed Under Section 351(a) of the PHS Act. Published August 2014. Accessed July 25, 2019.
  5. Lyman GH, Balaban E, Diaz M, et al. American Society of Clinical Oncology statement: biosimilars in oncology. J Clin Oncol. 2018;36(12):1260-1265.
  6. Amgen. FDA Approves Amgen And Allergan’s Kanjinti™ (trastuzumab-anns), a biosimilar to Herceptin® (trastuzumab) [press release]. Published June 13, 2019. Accessed July 11, 2019.
  7. Pfizer. US FDA approves Pfizer’s oncology biosimilar Trazimera™ (trastuzumab-qyyp), a biosimilar to Herceptin® [press release]. Published March 11, 2019. Accessed July 11, 2019.
  8. US Food and Drug Administration. FDA approves Herzuma as a biosimilar to Herceptin. Published December 14, 2018. Accessed July 11, 2019.
  9. US Food and Drug Administration. Drugs@FDA: FDA approved drug products: biologic license application (BLA): 761100. Accessed July 11, 2019.
  10. US Food and Drug Administration. FDA approves first biosimilar for the treatment of certain breast and stomach cancers. Last reviewed January 16, 2018. Accessed July 11, 2019.
  11. Yang J, Yu S, Yang Z, et al. Efficacy and safety of supportive care biosimilars among cancer patients: a systematic review and meta-analysis. BioDrugs. 2019;33(4):373-389.
  12. Peterson C; Express Scripts. Biosimilars in the US: more approvals but not access. Published January 10, 2019. Accessed July 11, 2019.