Bevacizumab Biosimilar Nears European Approval

Sean E. Harper, MD, executive vice president of Research and Development at Amgen

Sean E. Harper, MD

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of the bevacizumab (Avastin) biosimilar ABP 215 for the treatment of patients across several tumor types.

The positive opinion will now be reviewed by the European Commission. If approved, the biosimilar would be authorized for the following indications:

• Metastatic carcinoma of the colon or rectum, in combination with fluoropyrimidine-based chemotherapy;
• Metastatic breast cancer, in combination with paclitaxel;
• Unresectable advanced, metastatic or recurrent non-squamous non—small cell lung cancer (NSCLC), in combination with platinum-based chemotherapy;
• Unresectable advanced, metastatic or recurrent nonsquamous NSCLC, in combination with erlotinib;
• Advanced and/or metastatic renal cell cancer, in combination with interferon alfa-2a;
• Advanced, platinum-sensitive, or platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, in combination with carboplatin and paclitaxel, carboplatin and gemcitabine, and paclitaxel, topotecan, or pegylated liposomal doxorubicin
• Persistent, recurrent, or metastatic carcinoma of the cervix, in combination with paclitaxel and cisplatin, or alternatively, paclitaxel and topotecan.

“ABP 215 has the potential to provide healthcare professionals and appropriate patients across Europe access to high-quality, targeted cancer therapy,” Sean E. Harper, MD, executive vice president of Research and Development at Amgen, which co-develops ABP 215 with Allergan, said in a statement. "The positive CHMP opinion for ABP 215 marks the first time a bevacizumab biosimilar has been recommended for approval in the European Union, which is an exciting milestone for Amgen."

In September the FDA approved ABP-215 (bevacizumab-awwb; Mvasi) as the first biosimilar granted approval for the treatment of cancer in the United States. ABP-215 is indicated for the treatment of colorectal, lung, brain, kidney, and cervical cancers in adult patients.

The information the FDA reviewed included data from a pair of studies: the 3-arm, single-dose PK study 20110216 that compared ABP-215 with US- and EU-approved bevacizumab, and a comparative clinical study, 210120265. The second study compared ABP-215 and EU-approved bevacizumab in patients with advanced/metastatic NSCLC to support the demonstration of no clinically meaningful differences in terms of response, safety, purity, and potency.

In the PK study, 68 patients were assigned to ABP-215 and 67 each were assigned to the bevacizumab groups. All healthy male participants (N = 202) received an infusion of 3 mg/kg.

Investigators concluded that the 90% confidence interval (CI) for the ratios of geometric mean of AUC0_-∞, AUC0_-t, and C_MAX demonstrated PK similarity between ABP-215 and US- and EU-approved bevacizumab. C_MAX was 98.1 (90% CI, 93.7-102.8) between ABP-215 and US-approved bevacizumab, 102.9 (90% CI, 98.2-107.8) between ABP-215 and EU-approved bevacizumab, and 104.9 (90% CI, 100.1-109.9) between US-approved bevacizumab and EU-approved bevacizumab.

Study 20120265 was a randomized, double-blind study comparing ABP-215 (n = 328) and EU-approved bevacizumab (n = 314) in patients with advanced NSCLC. All patients received an infusion of 15 mg/kg every three weeks in combination with 6 AUC carboplatin and 200 mg/m2 paclitaxel for 6 cycles.

Overall response rate was 39% in the ABP-215 arm compared with 41.7% for EU-bevacizumab (risk ratio, 0.93; 90% CI, 0.8-1.09). There were 2 complete responses in each group, and 38.4% of the ABP-215 group had partial responses versus 41.1% in the bevacizumab group. Duration of response was 5.8 months for ABP-215 (95% CI, 4.9-7.7) compared with 5.6 months with bevacizumab (95% CI, 5.1-6.3).

Forty percent of patients in both groups experienced progression-free survival (PFS) events (HR, 1.03; 95% CI, 0.8-1.34). Median PFS was 6.6 months for ABP-215 (95% CI, 6.3-7.9) versus 7.0 months in the bevacizumab arm (95% CI, 6.6-8.2).

Trough serum concentrations (C_trough) were collected on cycle 1 through cycle 4, and cycle 6 pre-dose to describe the PK of ABP-215 and EU-approved bevacizumab. The study was not intended to evaluate PK similarity between the 2 arms, but investigators observed comparable Ctrough and inter-subject variability.

Investigators said safety outcomes were similar to the known toxicity profile of US-approved bevacizumab, and there were no meaningful differences in adverse events (AEs), serious AEs, deaths up to 30 days after last treatment dose, or treatment discontinuations. Reported grade 3/4 AEs were 42% in the ABP-215 arm and 44% in the bevacizumab arm. No grade 3/4 AE exceeded a 2% incidence rate.