FDA Approval Sought for Bevacizumab Biosimilar

Sean E. Harper, MD

A biologics license application (BLA) has been submitted for ABP-215, a biosimilar version of bevacizumab (Avastin), based on data from analytical, pharmacokinetic, clinical data, pharmacology, and toxicology data, according to a statement from Amgen and Allergan, the developers of the biosimilar.

A phase III study comparing ABP-215 and bevacizumab did not reveal a clinically meaningful difference between the medications as treatments for patients with non-squamous non-small cell lung cancer (NSCLC). The risk ratio for objective response rates (ORR) between therapies was 0.93. The two-sided 90% confidence interval for the risk ratio was 0.80 to 1.09, which was within the boundaries for equivalence, according to findings presented at the 2016 ASCO Annual Meeting.

The FDA will assign a review timeline within 60 days from the time of submission. A standard review for the agency takes 10 months following the 60-day window, placing a decision in November 2017. A priority review would shave 4 months off this timeline.

"ABP-215 is 1 of 4 oncology biosimilars in our pipeline, and today's BLA submission is an important milestone as Amgen seeks to expand our oncology portfolio," Sean E. Harper, MD, executive vice president of Research and Development at Amgen, said in a statement. "ABP-215 has the potential to offer an additional high-quality therapeutic option for patients diagnosed with cancer, continuing Amgen's mission of providing patients with vital medicines."

The phase III study enrolled 642 patients with non-squamous NSCLC to receive carboplatin and paclitaxel plus bevacizumab (n = 314) or ABP-215 (n = 328). The mean age of patients was 61.6 years. More patients in the bevacizumab arm were never smokers versus the biosimilar (24.2% vs 19.8%) and there were more current smokers in the biosimilar arm (30.5% vs 25.5%).

The ORR with ABP-215 was 39% compared with 41.7% with bevacizumab. There were 2 complete responses in each arm. The stable disease rates were 43.9% and 43.6%, for ABP-215 and bevacizumab, respectively.

Adverse events (AEs) of all-grades were experienced by 95.1% of those in the ABP-215 arm versus 93.5% of those treated with the reference product. The rate of grade ≥3 AEs were 42.9% and 44.3%, for the biosimilar and reference product, respectively. Serious AEs were experienced by 26.2% of those in the ABP-215 arm versus 23% of those treated with the reference product. An AE led to discontinuation of any component of the treatment regimen for 21% and 16.8% of patients, for ABP-215 and bevacizumab, respectively.

According to the companies, the application for ABP-215 was the first for a biosimilar of bevacizumab. If approved, ABP-215 would join a growing field of biosimilar medications, many of which are backed by phase III findings. There are currently over a dozen therapeutic biosimilars in phase III investigations.

"Allergan is committed to developing safe and effective therapies in certain critical disease areas," David Nicholson, Chief R&D Officer at Allergan, said in a statement. "The filing of ABP-215 is an important step forward in advancing a potential treatment option for patients with disorders susceptible to VEGF inhibition."

Amgen and Allergan are also collaborating on a biosimilar version of trastuzumab (Herceptin). Topline results from a phase III study comparing the trastuzumab biosimilar ABP-980 with the reference product as a neoadjuvant therapy for women with HER2-positive breast cancer were announced in July 2016. The primary endpoint of pathologic complete response, which was met, had a prespecified equivalence margin of +/-13% and the observed upper end of the confidence interval was 13.4%.

"We believe this study confirms no clinically meaningful differences between ABP-980 and trastuzumab, and we look forward to continued discussions with regulatory authorities," said Harper. "Biosimilars are approved based on the analytical, nonclinical and clinical data, and we believe that the totality of the evidence we've generated supports ABP-980 as highly similar to the reference product."

Biosimilars are meant to foster competition and lower prices. The first FDA-approved biosimilar in the United States was filgrastim-sndz (Zarxio), which gained approval in March 2015. This agent debuted at a 15% discount versus the reference product. At this point, the prices planned for ABP-980 and ABP-215 have not been announced.

Thatcher N, Thomas M, Paz-Ares L, et al. Randomized, double-blind, phase 3 study evaluating efficacy and safety of ABP 215 compared with bevacizumab in patients with non-squamous NSCLC. J Clin Oncol. 2016; 34 (suppl; abstr 9095).