FDA Approves First Biosimilar for Cancer Treatment

The FDA announced today that, for the first time, it has approved a biosimilar for the treatment of cancer.

ABP-215 (bevacizumab-awwb; Mvasi), a biosimilar for bevacizumab (Avastin) developed by Amgen and Allergan, is indicated for the treatment of colorectal, lung, brain, kidney, and cervical cancers in adult patients.

A biosimilar is a biological product that is demonstrated to be highly similar to an already-approved biological product, and that has no clinically meaningful differences in terms of safety, purity and potency from the reference product.

“Bringing new biosimilars to patients, especially for diseases where the cost of existing treatments can be high, is an important way to help spur competition that can lower healthcare costs and increase access to important therapies,” FDA Commissioner Scott Gottlieb, MD, said in a press release. “We’ll continue to work hard to ensure that biosimilar medications are brought to the market quickly, through a process that makes certain that these new medicines meet the FDA’s rigorous gold standard for safety and effectiveness.”

ABP-215 is approved for:

• First- or second-line treatment of metastatic colorectal cancer, in combination with 5-fluorouracil-based chemotherapy

• Second-line treatment of metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for patients who progressed on first-line bevacizumab

• First-line treatment of unresectable, locally advanced, recurrent, or metastatic nonsquamous non—small cell lung cancer (NSCLC), in combination with carboplatin and paclitaxel

• Glioblastoma, as a single agent for patients with progressive disease following prior therapy

• Metastatic renal cell carcinoma, in combination with interferon alfa

• Persistent, recurrent, or metastatic cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan

There are several pending applications for biosimilars to treat cancer awaiting FDA consideration, including one for MYL-1401O, a biosimilar for trastuzumab (Herceptin). The FDA is expected to rule on a biologics license application for MYL-1401O to treat HER-positive breast cancer, HER2-positive gastric cancer, and gastroesophageal junction cancer by the end of this year.

In July, the FDA’s Oncologic Drugs Advisory Committee voted 17-0 to recommend approval of ABP-215. Some committee members were concerned at the time about recommending approval for all 6 indications because all the data presented came from patients with advanced/metastatic NSCLC. They eventually determined that the pharmacokinetic (PK) data and method of action were consistent enough to warrant their support.

ODAC reviewed 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_-∞, AUC_0-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 (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.

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 C_trough 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.

In a press release, the FDA reported that, as with bevacizumab, ABP-215’s label includes a boxed warning regarding an increased risk gastrointestinal perforations, surgery and wound healing complications, and severe or fatal pulmonary, gastrointestinal, central nervous system and vaginal hemorrhage.

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).