Gary H. Lyman, MD, FASCO
In an effort to more clearly outline the introduction of biosimilars into the US healthcare system, the FDA published the Biosimilars Action Plan: Balancing Innovation and Competition in July 2018. Though this plan focuses mainly on development and industry standards, there is necessary information for clinicians who will be prescribing these agents.
Following several FDA approvals, oncologists are aware that biosimilars will soon be entering the cancer treatment landscape. There is trepidation though, said Gary H. Lyman, MD, FASCO, as the data regarding the similarity of these agents to the reference products are not in the public domain.
Additionally, the true reduction in cost associated with biosimilars is also unknown, but will likely not be visible until there are multiple biosimilars for a given reference product, according to Lyman. Regardless, the rate at which biosimilars are being produced indicates that they will play a role in the treatment of cancer in the years to come, particularly for patients who cannot currently afford the cost of healthcare.
"This is a part of the puzzle that we are trying to piece together on how to reduce costs and improve access to new cancer therapies,” said Lyman. “It is a high priority item, as far as I am concerned.”
Lyman added that one of the concerns he has once biosimilars are being used in patients with cancer is following postmarketing surveillance. Approvals of biosimilars requires less clinical data compared with a novel biologic, so patients treated with these agents should be observed for delayed toxicities or loss of long-term efficacy.
In a recent interview with OncLive
, Lyman, co-director of the Hutchinson Institute for Cancer Outcomes Research at Fred Hutchinson Cancer Research Center, interpreted the available information on biosimilars as it relates to the clinical oncology community.
OncLive: What are your thoughts on the guidance that the FDA has provided to clinicians thus far on biosimilars in oncology?
: There have been many efforts, including by the FDA, to inform clinicians about biosimilars. Their primary goal is to educate and hopefully reassure clinicians of the processes that they have in place, which are focused far more on preclinical data. These data must demonstrate that the molecule is very similar to the reference product, and that it behaves the same way in the laboratory and in animal models, as well as in limited clinical studies with pharmacokinetic and pharmacodynamic studies.
Additionally, there cannot be evidence of immunogenicity or antibodies. They have laid all of this out for clinicians—as to why they may grant an approval to a biosimilar without requiring multiple large clinical trials, like they generally require for an original biologic. The goal of the FDA is to both educate and reassure the clinicians, health systems, and patients, that safety and efficacy is preserved, and that these agents can be used as an alternative to the costlier originator products.
Having said this, it is pretty clear from discussions with colleagues that there remains concern, specifically with the limited clinical data available at the time of approval, and the fact that these are not generics. From the FDA's perspective, those small differences, which are inherent to biologic agents, do not have an impact on safety or efficacy and can therefore be used as an alternative to the reference product. Clinicians remain concerned because they have gotten comfortable with the original agent that was approved, based on the large-scale clinical trial data, and they are a little anxious about jumping to the biosimilar.
The first biosimilars available in the United States are myeloid growth factors that are not cancer treatments themselves but are used to support patients going through cancer treatment. These have been available in Europe for nearly a decade, and now in the United States for a couple years. As far as I can see, they are being utilized and integrated into the clinical practice guidelines of the use of myeloid growth factors.
Where it gets more problematic for some clinicians is how we now have biosimilars for cancer treatment. There is bevacizumab (Avastin) and trastuzumab (Herceptin), which are used as actual treatments for patients with cancer, and are known to have beneficial effects clinically and may even be curative in some settings. Clinicians will be encouraged to use biosimilar versions of these cancer treatments, although there is some hesitancy there.
One other issue is that the data available to the FDA at the time of the biosimilar approval needs to be available to the clinical community. We have had 1 or 2 biosimilars approved recently without public disclosure of the data that was reviewed by the FDA. Usually, an advisory committee, such as the FDA’s Oncologic Drugs Advisory Committee, reviews the data and makes a recommendation to the FDA and all that data are in the public domain.