The FDA has accepted a biologics license application for a proposed biosimilar for bevacizumab.
The FDA has accepted a biologics license application for a proposed biosimilar for bevacizumab (Avastin), according to an announcement by Mylan during its fourth quarter 2019 earnings call.
The company stated that the application is under review by the FDA, with an action date of December 27, 2020.
Mylan and Biocon co-develop the bevacizumab biosimilar MYL-1402O (Abevmy) which was approved by the Drug Controller General of India in November 2017 for all indications of reference bevacizumab, including for the treatment of patients with metastatic colorectal cancer (CRC), non—small cell lung cancer, glioblastoma, ovarian cancer, cervical cancer, and renal cell carcinoma, as part of specific regimens for Indian patients.
The approval was based on results of a comprehensive data package that demonstrated biosimilarity between the biosimilar and reference bevacizumab, including through analytical, pharmacokinetic, and pharmacodynamic studies and an India-specific, randomized, double-blind study in patients with mCRC. The biosimilar is approved in an injection formulation at 100-mg and 400-mg doses.
Results of a single-center, randomized, double-blind, 3-arm, parallel-group study of MYL-1402O were presented at the 2017 ASCO Annual Meeting.2 In 111 healthy male volunteers, investigators sought to establish pharmacokinetic (PK) similarity between the bevacizumab biosimilar (arm A) and EU-sourced bevacizumab (arm B) and US-sourced bevacizumab (arm C), as well as between EU-sourced bevacizumab and US-sourced bevacizumab.
Patients were randomized to receive intravenous treatment in 1 of the 3 arms at a 1-mg/kg dose over 90 minutes. Dosage was selected based on the lower dose in the linear range of PK and acceptable safety.
Bioequivalence was determined if the 90% confidence intervals (CIs) of the ratios were within 80% to 125%. Investigators also evaluated area under the curve (AUC)0-t, Cmax, tmax, elimination rate constant, and half-life were assessed as secondary PK factors.
Results showed that bioequivalence was demonstrated between arms A and B, arms A and C, and between arms B and C. The least squares mean ratios were close to 1, and 90% CIs were within 0.80 to 1.25 for all 3 comparisons. Moreover, the secondary PK parameters were also found to be comparable with the 90% CIs for ratios of AUC0-t and Cmax within 80% to 125%.
Regarding safety, 313 treatment-emergent adverse events (TEAEs), which were grades 1/2 in severity, were reported across all arms: arm A (89%), arm B (78%), and arm C (76%). The majority of the TEAEs were consistent with prior clinical findings of bevacizumab, and no serious or unexpected TEAEs were reported.
Two other bevacizumab biosimilars are approved by the FDA: bevacizumab-awwb (Mvasi) and bevacizumab-bvzr (Zirabev), both of which launched in the United States in 2019. Moreover, a supplemental biologics license application was accepted by the FDA in November 2019 for the bevacizumab biosimilar SB8.
In the fourth quarter 2019 earnings call, Mylan also announced that it had submitted a European application for the bevacizumab biosimilar, adding that it is currently in the validation stage with authorities.