FDA Approval Sought for EirGenix Trastuzumab Biosimilar for HER2+ Breast and Gastric Cancers

A biologics license application has been submitted to the FDA seeking the approval of a proposed biosimilar for trastuzumab (Herceptin), a monoclonal antibody that is utilized in the treatment of patients with HER2-positive breast cancer and metastatic gastric cancers.¹

The biosimilar, referred to as EG12014/EGI014, was developed by EirGenix, Inc., and it is intended to be administered intravenously at a dose of 150 mg. The application is seeking the product’s approval for the same indications as the reference product, based on a comprehensive data package that is comprised of analytical, preclinical, and clinical information.

“Approximately 15% to 20% of all patients with breast cancer have tumors that are HER2 positive and, as these tumors tend to grow more quickly than HER2-negative tumors, getting treated swiftly can be lifesaving,” Florian Bieber, global head of Biopharmaceuticals Development at Sandoz, stated in a press release. “Trastuzumab is standard of care, so if approved, we will introduce more competition aiming to broaden access to this important therapy and liberate healthcare resources that can be used to fund other innovative medicines in the United States.”

In an ongoing, multicenter, double-blind, phase 3 trial (NCT03433313), investigators set out to compare the safety and efficacy of the EG12014 with trastuzumab as neoadjuvant treatment for 12 weeks, followed by surgery and subsequent EG12014 or trastuzumab adjuvant treatment for up to 12 months.²

To be eligible for enrollment, patients needed to be between the ages of 18 and 65 years and have histologically confirmed invasive carcinoma of the breast, operable disease with planned surgical resection of the tumor and sentinel or axillary lymph nodes, and unilateral, measurable tumor of the breast that was greater than 2 cm in diameter.

Moreover, patients needed to have tumors with HER2 positivity, known estrogen and progesterone receptor status, as well as acceptable bone marrow, hepatic, and renal function. Patients also needed to have an ECOG performance status of 0 or 1 and a left ventricular ejection fraction that was 55% or higher.

If patients had bilateral breast cancer, metastases beyond sentinel or axillary lymph nodes, received prior treatment for invasive malignant disease or other concomitant malignancy beyond basal cell carcinoma of the skin, or prior trastuzumab, they were excluded.

Other exclusion criteria included a history of hypersensitivity to drugs with comparable chemical structures to trastuzumab or being positive for hepatitis B virus, hepatitis C virus, or human immunodeficiency virus.

In the neoadjuvant phase of the trial, a total of 807 patients were randomized to 1 of 2 cohorts. The first arm received epirubicin at a dose of 90 mg/m2 and cyclophosphamide at a dose of 600 mg/m² every 3 weeks for 4 cycles, followed by EG12014.³ The second arm was administered the same regimen of chemotherapy but with the reference product instead of the biosimilar.

For both arms, trastuzumab was given at a loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg. Moreover, both treatment arms were also given paclitaxel at a dose of 175 mg/m2 every 3 weeks for 4 cycles.

Participants then underwent surgery and pathologic complete response (pCR), the primary end point of the research, was evaluated.

In the adjuvant phase of the trial, participants went on to receive the biosimilar or the reference product at a loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg for a total of 1 year of trastuzumab treatment.

Results presented during the 2021 San Antonio Breast Cancer Symposium showed that the trial met its primary end point of pCR at time of surgery, with a relative risk ratio of 0.992 (90% CI, 0.880-1.118) between the treatment arms. Secondary end points of tumor eradication from the breast and lymph nodes were also met.

The objective clinical response, event-free survival, overall survival, and safety data proved to be comparable between the arms, supporting equivalence of the products.

As part of a license agreement signed in April 2019, EirGenix, Inc. is responsible for the development and manufacturing of the biosimilar and Sandoz will commercialize the product once it receives regulatory approval in all markets except for China and Taiwan.

References

1. Sandoz submits biologics license application for proposed biosimilar trastuzumab to US FDA. News release. Novartis; December 20, 2021. Accessed December 21, 2021. https://bit.ly/3FpJbY0
2. Efficacy and safety study of EG12014 compared with Herceptin in subjects with HER2 positive early breast cancer. ClinicalTrials.gov. Updated April 6, 2020. Accessed December 21, 2021. https://clinicaltrials.gov/ct2/show/NCT03433313
3. Grohmann-Izay B, Huang C-S, Dzagnidze G, et al. A phase III, randomized, multicenter, double-blind study to compare efficacy and safety of EG12014 (EirGenix trastuzumab) with Herceptin as neoadjuvant treatment in combination with anthracycline/paclitaxel-based systemic therapy in patients with HER2-positive early breast cancer - a multinational phase III study conducted during the COVID-19 pandemic. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; virtual. Abstract P2-13-17.