Regulatory Decisions, New Data Propel Progress With Biosimilars in Oncology

The uptick of biosimilars has led to a surge of new data and regulatory decisions in recent years, with a focus on similarity between biosimilars and their reference products while reducing healthcare costs. This week, data on subcutaneous formulations of one biosimilar and long-term experience with another were provided, as well as an authorization of a trastuzumab (Herceptin) biosimilar in Canada.

Here are the updates over the past week with biosimilars in oncology.

Health Canada Approves Trastuzumab Biosimilar

Health Canada has granted authorization to the trastuzumab biosimilar CT-P6 (Herzuma; trastuzumab-pkrb) for the treatment of patients with HER2-positive early breast cancer, metastatic breast cancer, and metastatic gastric cancer.¹

The approval was based on an extensive review of a comprehensive data package, which included foundational analytical similarity data, nonclinical data, clinical pharmacology, immunogenicity, clinical efficacy, and safety data. Part of the package included a phase III, randomized study, results of which showed that a similar proportion of patients achieved pathological complete response with the biosimilar as with the reference trastuzumab.

Moreover, updated results from a posthoc subgroup analysis of the adjuvant period of treatment in this trial were recently announced. When used in the adjuvant setting, the biosimilar has comparable efficacy and safety to the reference at 1 year.²

The FDA granted an approval to CT-P6 in December 2018 for the treatment of patients with HER2-overexpressing breast cancer.

Subcutaneous Epoetin Alfa Demonstrates Noninferiority to Reference Product

Following the FDA approval of the epoetin alfa (Epogen; Procrit) biosimilar Retacrit (epoetin alfa-epbx) in 2018 for the treatment of anemia caused by chronic kidney disease, chemotherapy, or the use of zidovudine in patients with HIV, the agency requested that the biosimilar’s developer, Pfizer, provide data on subcutaneous administration.

Results from that study, which were published in Kidney International Reports, show that the subcutaneous administration of the biosimilar has similar safety and efficacy to subcutaneous administration of the reference agent.³

In the trial, 320 adult patients with end-stage kidney disease and anemia and were stable on intravenous or subcutaneous epoetin alfa were randomized 1:1 to receive the biosimilar or the reference epoetin alfa. Data from the primary analysis in the intent-to-treat population showed that the confidence interval (CI) between treatment groups in mean weekly hemoglobin levels during the final 4 weeks of treatment was 0.04 g/dL (−0.17 to 0.24 g/dL) and the difference in mean weekly epoetin dose per kg of body weight was −2.34 U/kg weekly (−14.51 to 9.82 U/kg weekly).

Results showed that 95% CIs were contained within the prespecified equivalence margins of ±0.5 g/dL for weekly hemoglobin and ±45 U/kg per week for weekly epoetin dose per kg of body weight.

Long-Term Experience With Filgrastim Biosimilar Showcase Efficacy, Safety

Ten years of experience with the first filgrastim (Neupogen) biosimilar (Zarzio), which was first approved by the European Commission in 2009, demonstrates the strong scientific basis for the extrapolation of indications for biosimilars, according to a recent review published in BioDrugs.⁴

Phase III confirmatory data with this biosimilar have been published in patients with breast cancer who are receiving myelosuppressive chemotherapy, and an approval of the biosimilar was then granted for all indications of the reference agent.

Overall, the data supported the totality of evidence and can reassure healthcare professionals with the efficacy and safety of the filgrastim biosimilar. Moreover, the extrapolation of data, and specifically acceptance of this biosimilar for widespread use, also has led to a paved path for others to recognize new biosimilars.

References

1. Celltrion and Teva announce FDA approval of Herzuma (trastuzumab-pkrb), a biosimilar to Herceptin, for the treatment of HER2-overexpressing breast cancer for certain indications [news release]. Incheon, South Korea, and Jerusalem, Israel: Celltrion. Published December 14, 2018. https://www.celltrion.com/en/pr/reportDetail.do?seq=534&rel=0" . Accessed December 17, 2018.
2. Esteva FJ, Baranau YV, Baryash V, et al. Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial [published online August 19, 2019]. Cancer Chemother Pharmacol. doi: 10.1007/s00280-019-03920-4.
3. Fishbane S, Spinowitz BS, Wisemandle WA, Martin NE. Randomized controlled trial of subcutaneous epoetin alfa-epbx versus epoetin alfa in end-stage kidney disease. Kidney Int Rep. 2019;4(9):1235-1247. doi: 10.1016/j.ekir.2019.05.010.
4. Gascon P, Krendyukov A, Mathieson N, Mathieson N, Natek M, Aapro M. Extrapolation in practice: lessons from 10 years with biosimilar filgrastim [published online August 22, 2019]. BioDrugs. doi: 10.1007/s40259-019-00373-2.