Abstract
An FDA expert panel recommended approval of Mylan's MYL-14010, a biosimilar candidate for Genentech's trastuzumab, putting it on track to become the first approved biosimilar for cancer. Experts predict that biosimilars will lead to lower drug prices, but caution that the savings won't be as dramatic as that seen with generics.
The FDA's Oncologic Drugs Advisory Committee (ODAC) recently recommended approval of MYL-14010 (Mylan), a trastuzumab (Herceptin; Genentech) biosimilar. It is one of several trastuzumab biosimilars in the pipeline, potentially leading to lower costs as well as improved access to biologic drugs for women with HER2-positive breast cancer.
The ODAC panel voted unanimously for approval of MYL-14010 based on analytic data showing its high similarity to Genentech's trastuzumab and results from the Heritage Study, a head-to-head comparison of the two agents in 458 women with HER2-positive metastatic breast cancer. The overall response rate at 24 weeks was 69.6% in the biosimilar group versus 64% in the trastuzumab group, a non–statistically significant difference. In addition, they had nearly identical side-effect profiles.
If sanctioned by the FDA, MYL-14010 would become the first approved biosimilar to treat cancer. In 2015, filgrastim-sndz (Zarxio; Sandoz), a version of filgrastim (Neupogen; Amgen) for treating neutropenia in patients with cancer, became the first biosimilar to earn FDA approval.
Others are developing versions of Herceptin—which loses patent protection in 2019—including Celltrion, which recently reported positive phase III results for CT-P6, and Pfizer, which is conducting a phase III trial of its candidate, PF-05280014. Biosimilars are also in the works for two other commonly used cancer drugs made by Genentech: bevacizumab (Avastin), an angiogenesis inhibitor, and rituximab (Rituxan), an anti-CD20 drug.
The hope is that biosimilars will create price competition and make innovative therapies more widely available. However, estimates of the potential savings vary widely. For example, a 2014 report by RAND Corporation predicts that biosimilars will cut drug spending by $44.2 billion between 2014 and 2024, whereas another report by Express Scripts pegs potential savings at $250 billion for the same time period.
Compared with generics—which typically result in immediate significant price discounts over the original drugs—biosimilars likely will have a more modest cost impact, experts say. Whereas generic versions of small-molecule drugs are exact chemical copies of the originals, biosimilars are based on complex large-molecule biologics that must be synthesized from living organisms—making them more difficult and costly to produce.
“It's impossible to exactly match a biosimilar with the original biologic,” says Emily Shacter, PhD, an independent consultant with ThinkFDA in Takoma Park, MD. “A living cell line must be engineered to make a protein that looks very much like a protein made in a different cell system with a different gene construct, and this is very difficult to do.” However, she adds, it is possible to achieve an adequate match and be reasonably certain that the biosimilar and the original drug yield comparable clinical performance.
Even so, some have wondered whether different versions of the same drug might have different effects in patients over time. However, notes Shacter, the rigor of the FDA review and approval process is designed to minimize that risk.
Results from clinical trials are critical to the approval process, says Debasish Tripathy, MD, chair of the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston. For biosimilars, the FDA considers response rate as a primary endpoint in clinical trials, and confidence intervals must overlap or show specific upper or lower 95% confidence interval boundaries in relation to the approved biologic in order to demonstrate similarity, he explains. Once that criterion is met, secondary endpoints are factored into the analysis, including median progression-free and overall survival and toxicities.
Endpoints aside, Tripathy says, patients who have kept their disease in check for years with trastuzumab may be hesitant to switch.
“Our ability to measure a biosimilar's equivalency is limited,” notes Tripathy. “Nonetheless, the overall benefits for society as a whole by making drugs more accessible likely outweigh the small possibility that one drug might be slightly worse than another.” –Janet Colwell
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