Biosimilar Trastuzumab, Ogivri, and Its Reference in Combination With Pertuzumab Show Similar Activity

The Center for Biosimilars Staff

While biosimilars approved by regulators have been shown to have no clinically meaningful differences from their reference products, this week, during the San Antonio Breast Cancer Symposium, held in San Antonio, Texas, researchers will report reassuring data for biosimilar trastuzumab, Ogivri, showing that the combination of the biosimilar with pertuzumab is highly similar to the combination of the reference drug with pertuzumab.

Trastuzumab, used in the treatment of HER2-positive breast cancer, is given in some regimens together with pertuzumab to improve clinical benefit; the 2 antibodies bind to HER2 at different subdomains and have a synergistic effect. Biosimilar trastuzumab has also made combination trastuzumab/pertuzumab treatment more affordable, allowing greater patient access.

While biosimilars approved by regulators have been shown to have no clinically meaningful differences from their reference products, this week, during the San Antonio Breast Cancer Symposium, held in San Antonio, Texas, researchers will report reassuring data for biosimilar trastuzumab, Ogivri, showing that the combination of the biosimilar with pertuzumab is highly similar to the combination of the reference drug with pertuzumab.

In the study, researchers used 2 cancer cell lines, BT474 and HCC1954, to perform all tests. Fluorescence-activated cell sorting—based antigen binding evaluations and live cell imaging were performed for the reference trastuzumab, the biosimilar, and pertuzumab in combinations at concentrations of 0, 10, 100, and 1000 ng/mL.

Predefined acceptance criteria for the ligand-binding assay (LBA) was ±20%. Proliferation and CDC complement-dependent cytotoxicity (CDC) assays for the reference and biosimilar trastuzumab were tested at concentrations of 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mcg/mL in combination with pertuzumab at concentrations of 1, 10, and 100 mcg/mL; the number of viable cells was also estimated. Equivalence was stablished if the 90% CI of the difference between means fell within ±20%.

In the BT474 cell line:

  • Using the biosimilar trastuzumab plus pertuzumab combination, the mean LBA percentage of cells was 69.6 (±0.3) versus 73.5 (±0.3) for the reference plus pertuzumab combination (90% CI for the difference between means, —4.5 to –3.4).
  • The mean proliferation (ratio) was 65.3 (±2.5) versus 69.6 (±1.2) for the 2 combinations (90% CI for the difference between means, —7.2 to –0.3).
  • The mean CDC percentage of cells was 58.2 (±0.1) and 62.8 (±1.1) for the 2 combinations (90% CI for the difference between means, —5.8 to –3.2)

In the HCC1954 cell line:

  • Using the biosimilar trastuzumab plus pertuzumab combination, the mean LBA percentage of cells was 94.2 (±0.3) versus 88.1 (±0.1) for the reference plus pertuzumab combination (90% CI for the difference between means, 5.8-6.4).
  • The mean proliferation (ratio) was 80.5 (±1.9) versus 87.8 (±5.4) for the 2 combinations (90% CI for the difference between means, —14.3 to –0.3).
  • The mean CDC percentage of cells was 49.8 (±0.1) and 52.9 (±1.0) for the 2 combinations (90% CI for the difference between means, —4.3 to –1.9).

According to the authors, these results show that biological activity showed the same patterns in the presence of both reference and biosimilar trastuzumab in combination with pertuzumab, and that the combinations are highly similar.

Reference

Pimentel FF, Toledo JS, Gonçalves J, et al. Comparative evaluation of a trastuzumab biosimilar or originator trastuzumab in association with pertuzumab: binding and biological activities in cell culture-based assays. Presented at: San Antonio Breast Cancer Symposium, December 10-14, 2019; San Antonio, TX. Abstract P5-05-08.