Bevacizumab Biosimilar Receives Approval in the European Union

The European Medicines Agency (EMA) has approved Avzivi (BAT1706), a biosimilar referencing bevacizumab (Avastin), according to an announcement from Bio-Thera Solutions.¹

Avzivi is approved for the following indications in Europe:

• in combination with fluoropyrimidine-based chemotherapy for the treatment of adult patients with metastatic carcinoma of the colon or rectum
• in combination with paclitaxel for the first-line treatment of adult patients with metastatic breast cancer
• in combination with capecitabine for first-line treatment of adult patients with metastatic breast cancer for whom other chemotherapy options such as taxanes or anthracyclines are not appropriate; those given adjuvant taxane- and anthracycline-containing regimens within the 12 months are excluded from treatment with Avzivi plus capecitabine.
• in combination with platinum-based chemotherapy for the first-line treatment of adult patients with unresectable advanced, metastatic, or recurrent non–small cell lung cancer (NSCLC) other than predominantly squamous histology
• in combination with erlotinib (Tarceva) for the first-line treatment of adult patients with unresectable advanced, metastatic, or recurrent nonsquamous NSCLC harboring EGFR activating mutations
• in combination with interferon alfa-2a for the first-line treatment of adult patients with advanced and/or metastatic renal cell cancer
• in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with advanced FIGO stage IIIB/C or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer
• in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel in adult patients with platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer at first recurrence who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGFR-targeted agents
• in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin in adult patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens and have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGFR-targeted agents
• in combination with paclitaxel and cisplatin or paclitaxel and topotecan in adult patients with persistent, recurrent, or metastatic carcinoma of the cervix who cannot receive platinum-based therapy

“The EMA approval of [Avzivi] is another significant accomplishment for Bio-Thera as it marks Bio-Thera’s second EMA-approved product” Shengfeng Li, chief executive officer at Bio-Thera Solutions, stated in a news release. “As our biosimilar pipeline continues to mature, we intend to seek more biosimilar approvals, expanding patient access to important therapies.”

The European approval follows a positive recommendation from the EMA’s Committee for Medicinal Products for Human Use.²

In December 2023, the FDA approved Avzivi for use in the United States.³

In a phase 3 trial (NCT03329911), patients with advanced nonsquamous NSCLC were randomly assigned to receive Avzivi plus paclitaxel and carboplatin or European Union–sourced bevacizumab plus paclitaxel and carboplatin. Findings showed that patients treated with Avzivi plus chemotherapy (n = 325) experienced an overall response rate (ORR) at week 18 of 48.0% (95% CI, 42.5%-53.6%) vs 44.5% (95% CI, 39.0%-50.1%) for those given bevacizumab plus chemotherapy (n = 324; odds ratio, 1.08; 90% CI, 0.94-1.24).⁴

The multicenter, randomized, double-blind trial enrolled patients at least 18 years of age with histologically or cytologically confirmed stage IV or recurrent nonsquamous NSCLC that did not harbor EGFR mutations or ALK rearrangements who did not receive prior systemic therapy for metastatic disease. Patients needed to have at least 1 measurable lesion per RECIST 1.1 criteria; an ECOG performance status of 0 or 1; a life expectancy of more than 3 months; and adequate hematological, hepatic, and renal function.

Key exclusion criteria included small cell carcinoma of the lung; known ROS1-positive tumors; prior therapy with monoclonal antibodies or small molecule inhibitors targeting VEGF or VEGFR; and known, symptomatic or untreated brain metastases or other central nervous system metastases.

Patients were randomly assigned 1:1 to received 15 mg/kg of Avzivi plus paclitaxel and carboplatin once every 3 weeks for up to 6 cycles; or 15 mg/kg of bevacizumab plus paclitaxel and carboplatin once every 3 weeks for up to 6 cycles. During cycle 1, Avzivi or bevacizumab were administered alone on day 1, followed by paclitaxel and carboplatin on day 2. Avzivi or bevacizumab were given prior to chemotherapy on day 1 of subsequent cycles. Patients who achieved a response or stable disease following the completion of 6 cycles of chemotherapy received Avzivi or bevacizumab as maintenance for up to 12 months.

ORR at week 18 per blinded central imaging review (BCIR) assessment served as the trial’s primary end point. Secondary end points included BCIR-assessed ORR at weeks 6 and 12; best ORR at the end of study; duration of response; investigator-assessed progression-free survival (PFS) and overall survival (OS) at 12 months; duration of PFS and OS; and safety.

Additional data showed that the median PFS was 8.1 months (95% CI, 7.1-8.3) for the Avzivi arm vs 7.7 months (95% CI, 6.2-8.3) for the bevacizumab arm (stratified HR, 0.915; 95% CI, 0.741-1.132; P = .412). The 12-month PFS rates were 20.7% (95% CI, 14.2%-28.1%) and 21.8% (95% CI, 15.0%-29.5%), respectively.

The median OS was 16.4 months (95% CI, 13.9–not reached [NR]) in the Avzivi arm compared with 18.5 months (95% CI, 14.0-NR) for the bevacizumab arm (stratified HR, 0.916; 95% CI, 0.693-1.210; P = .536). The respective 12-month OS rates were 66.7% (95% CI, 60.0%-72.6%) and 65.9% (95% CI, 59.4%-71.6%).

Patients in the Avzivi group achieved a median DOR of 6.9 months (95% CI, 5.7-7.6) vs 7.1 months (95% CI, 5.5-9.0) for those in the bevacizumab group (stratified HR, 1.094; 95% CI, 0.803-1.491; P = .566). The respective 12-month DOR rates were 10.9% (95% CI, 1.3%-32.3%) and 20.4% (95% CI, 8.0%-36.7%).

Regarding safety, any-grade treatment-emergent adverse effects (TEAEs) occurred in 97.2% of patients in the Avzivi arm vs 98.1% of patients in the bevacizumab arm. The rates of TEAEs deemed related to Avzivi or bevacizumab were 59.7% and 57.7%, respectively. The rate of serious TEAEs related to Avzivi was 9.8% vs 9.3% for bevacizumab. The rates of treatment discontinuation deemed related to Avzivi or bevacizumab and chemotherapy were similar between the 2 arms.

References

1. European Medicines Agency (EMA) approves Bio-Thera Solutions’ BAT1706 (Avzivi, bevacizumab), a biosimilar referencing Avastin. News release. Bio-Thera Solutions. July 30, 2024. Accessed July 30, 2024. https://www.bio-thera.com/plus/view.php?aid=1028
2. Bio-Thera Solutions receives positive CHMP opinion for Avzivi (bevacizumab), a biosimilar referencing Avastin. News release. Bio-Thera Solutions. June 3, 2024. Accessed July 30, 2024. https://www.bio-thera.com/plus/view.php?aid=1005
3. FDA approves Bio-Thera Solutions’ Avzivi (bevacizumab-tnjn), a biosimilar referencing Avastin. News release. Bio-Thera Solutions. December 7, 2023. Accessed July 30, 2024. https://www.bio-thera.com/plus/view.php?aid=919
4. Chen L, Rangel JDG, Cil T, et al. Efficacy and safety of the proposed bevacizumab biosimilar BAT1706 compared with reference bevacizumab in patients with advanced nonsquamous non-small cell lung cancer: a randomized, double-blind, phase III study. Cancer Med. 2023;12(22):20847-20863. doi:10.1002/cam4.6664