Bevacizumab Biosimilar Aybintio Receives Positive European Opinion

The Committee for Medicinal Products for Human Use (CHMP) has recommended approval of Aybintio, a bevacizumab (Avastin) biosimilar for the treatment of patients with the same types of cancer for which the reference product is indicated in the European Union, according to Samsung Bioepis Co, Ltd.¹

Specifically, the agent is recommended for use in those with metastatic colorectal cancer (CRC), metastatic breast cancer, non–small cell lung cancer (NSCLC), advanced and/or metastatic renal cell carcinoma (RCC), epithelial ovarian, fallopian tube, and primary peritoneal cancer, and cervical cancer.

The application is based on a comprehensive data package and totality of evidence which was comprised of analytic, pharmacokinetic and clinical findings, in addition to pharmacology and toxicology information. Collectively, these data indicate that the biosimilar is highly similar to the reference product with no clinically meaningful differences detected.

“We are delighted by our progress in expanding patient access to high-quality biopharmaceuticals,” Hee Kyung Kim, senior vice president of Clinical Science and Regulatory Affairs at Samsung Bioepis said in a press release. “Once approved, Aybintio will be a valuable treatment option for different types of cancers, potentially helping many patients across Europe.”

In September 2019, the company submitted a biologics license application to the FDA, which was accepted just 2 months later. Data from a phase 3 trial (NCT02754882) examining Aybintio, previously referred to as SB8, presented at the 2019 ESMO Congress indicated that the agent demonstrated similar efficacy with regard to best overall response rate (ORR) risk ratio versus bevacizumab in patients with metastatic or recurrent nonsquamous NSCLC.²

In the multicenter, double-blind trial, a total of 763 patients with metastatic or recurrent nonsquamous disease were randomized 1:1 to the biosimilar (n = 379) or reference bevacizumab (n = 384) in combination with paclitaxel and carboplatin every 3 weeks, followed by the biosimilar or bevacizumab as maintenance treatment. Patients received treatment until their disease progressed, they experienced intolerable toxicity, or they completed treatment for the duration of 1 year following randomization of the last patient.

To participate in the trial, patients had to be ≥18 years old, have an ECOG performance score of 0 or 1, have histologically confirmed metastatic or recurrent nonsquamous disease, and have ≥1 measurable lesion per RECIST v1.1 criteria. They also had to be able to receive bevacizumab, carboplatin, and paclitaxel. Patients were excluded if they had a small cell carcinoma of the lung or squamous cell carcinoma diagnosis, had tumors that harbored EGFR or ALK aberrations, were at increased risk of bleeding, or if they had a history of first-line chemotherapy in the metastatic or recurrent setting.

The primary end point of the trial was best ORR by 24 weeks of chemotherapy. Secondary end points of the trial were comprised of progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, pharmacokinetics, and immunogenicity. In the full analysis set, the risk ratio was assessed, and the risk difference was computed in the per-protocol set.

Data demonstrated that in the best ORR was 47.6% with the biosimilar and 42.8% with reference bevacizumab in the full analysis set, and the risk ratio was 1.11 (90% CI, 0.975-1.269); notably, this fell within the predefined equivalence margin (0.737-1.357).

The best ORR in the per-protocol set, was 50.1% with the biosimilar versus 44.8% with the reference product. The risk difference was 5.3% (95% CI, -2.2%-12.9%), of which the lower margin was contained with and the upper margin was outside the predefined equivalence margin of (95% CI, -12.5%-12.5%).

Moreover, the median PFS was 8.50 months versus 7.90 months with the biosimilar and the reference product, respectively, and the median OS was 14.90 months and 15.80 months, respectively. The median DOR reported with the biosimilar was 5.60 months versus 5.85 months with bevacizumab.

With regard to safety, the overall incidence of treatment-emergent adverse events (TEAEs) was found to be similar between the biosimilar and reference arms, at 92.1% and 91.1%, respectively. The TEAEs that were reported most often were alopecia, anemia, and nausea.

Notably, C_trough and C_max, and the incidence of overall antidrug antibodies were found to be comparable between the treatment arms, at 16.1% with the biosimilar and 11.0% with reference bevacizumab.

In June 2019, PF-06439535 (bevacizumab-bvzr; Zirabev), another bevacizumab biosimilar, was approved by the FDA for use in patients with metastatic cCRC, unresectable, locally advanced, recurrent, or metastatic nonsquamous NSCLC, recurrent glioblastoma, metastatic RCC, and persistent, recurrent, or metastatic cervical cancer.

References

1. Samsung Bioepis receives positive CHMP opinion for Aybintio (bevacizumab). News release. Samsung Bioepis Co, Ltd. June 26, 2020. Accessed June 26, 2020. bit.ly/31hD9Y9.
2. Reck M, Luft A, Bondarenko I, et al. A phase III study comparing SB8, a proposed bevacizumab biosimilar, and reference bevacizumab in patients with metastatic or recurrent non-squamous NSCLC. Ann Oncol. 2019;30(suppl 5):1565P. doi:10.1093/annonc/mdz260.087