Positive efficacy and safety results observed with the proposed trastuzumab biosimilar, EG12014 in HER2-positive early breast cancer, has led the developer to plan regulatory filings in the United States, Europe, and China.
EG12014, a proposed biosimilar to trastuzumab (Herceptin) achieved an equivalent pathologic completed response rate (pCR) to trastuzumab as treatment of patients with HER2-positive early breast cancer, meeting the primary end point of a phase 3 clinical trial (NCT03433313), announced EirGenix, Inc, in a press release.
In addition to efficacy, the trastuzumab biosimilar also demonstrated a comparable safety profile, leading the company to prepare to file a Biologics License Application with the FDA, a Market Approval Application with the European Medicines Agency, and a New Drug Application with the Republic of China Food and Drug Administration.
The phase 3 clinical trial is a multi-national, multi-center, randomized, double-blind study that assessed the use of EG12014 in combination with anthracycline and paclitaxel systemic therapy in 807 patients. The secondary end points of the study include pCR at the time of surgery, event-free survival, overall response, overall survival, and the safety determined by the incidence of adverse events. Those enrolled were randomized 1:1 to receive either EG12014 or trastuzumab in combination with chemotherapy every 3 weeks for 12 weeks during cycles 1 through 4. Following the first 4 cycles of treatment, patients then received EG12014 or trastuzumab in combination with paclitaxel every 3 weeks for 12 weeks during cycle 5 through 8.
Treatment was administered in the neoadjuvant setting after which patients were scheduled to undergo resection of tumors found in the breasts or lymph nodes. Surgery was 3 to 6 weeks after neoadjuvant therapy. Then, patients were able to continue treatment on trastuzumab 2 to 6 weeks following surgery for a total of 12 months on treatment with trastuzumab. After the final dose of trastuzumab was administered in the study, patients were then followed for an additional 20 weeks for the safety analysis.
To be eligible for the study of EG12014 plus anthracycline and paclitaxel, patients were required to be females between the ages of 18 and 65 years old with histologically confirmed invasive carcinoma of the breast that is operable, measurable, and positive for a HER2 mutation. Other qualifiers included known estrogen receptor and progesterone receptor status at the time of entry into the study, adequate bone marrow, hepatic, and renal function, adequate laboratory values, an ECOG performance status of 0 or 1, and left ventricular ejection fraction of ≥55% according to a multiple-gated acquisition scan or echocardiography.
Patients were excluded from the study if they were diagnosed with bilateral breast cancer, were pregnant or lactating, had metastases, angina pectoris or arrhythmia requiring medication, hepatitis B or C virus, HIV, or other serious illnesses. In terms of prior therapy, patients who received or invasive malignant disease or other concomitant malignancy other than for Basal cell carcinoma were excluded as were patients who received prior trastuzumab, or an investigational agent within 30 days of starting treatment in the study. Further, patients with a history of hypersensitivity to drugs with similar chemical structures to trastuzumab and those with a history or known current problems with the abuse of drugs or alcohol were excluded from the study.
“Current demand for complex biological drugs has increased and will continue to rise in the future. With the drug patents of major biological drugs set to expire in the near future, the development of biosimilars has been greatly encouraged,” the company wrote in the press release.
If EG12014 is granted FDA approval as a trastuzumab biosimilar for the treatment of HER2-positive early breast cancer, it will join the 5 other FDA-approved trastuzumab biosimilars available for HER2-positive breast cancer. Other FDA-approved trastuzumab biosimilars include trastuzumab-anns, trastuzumab-qyyp, trastuzumab-dttb, trastuzumab-pkrb, and trastuzumab-dkst,
Positive phase iii clinical results for EirGenix's proposed trastuzumab biosimilar. News release. EirGenix, Inc. March 24, 2021. Accessed March 27, 2021. https://bit.ly/3coJsy5