Ivo Abraham, PhD, RN, a professor with the University of Arizona Health Sciences in the Department of Pharmacy Practice, discusses the current state of the granulocyte-colony stimulating factor (G-CSF) sector of the biosimilar market.
Ivo Abraham, PhD, RN, a professor with the University of Arizona Health Sciences in the Department of Pharmacy Practice, discusses the current state of the granulocyte-colony stimulating factor (G-CSF) sector of the biosimilar market. Abraham is also a health care consultant and co-founder at Matrix45.
What separates the G-CSF (granulocyte-colony stimulating factor) biosimilars from other oncology biosimilars in terms of market activity? And what is to account for these differences?
The G-CSFs, whether it is filgrastim or pegfilgrastim, were actually the first biosimilars on the US market. So, the first approval was for Zarxio (filgrastim-sndz) in 2015. That was really the breakthrough of biosimilars on the US market. Historically, the first biosimilars were all in what we call the supportive cancer care area. So, this is not to treat cancers but to support patients being treated with for their cancers. Think of the G-CSF biosimilars as kind of a horizontal products that cut across different tumor types and actually cut across lots of treatment regimens.
The other biosimilars, the more of what we would call therapeutic biosimilars, are only now beginning to be approved, [including] bevacizumab and trastuzumab. So, this is really the first generation of monoclonal antibodies that are now going to have biosimilar [competition]. Think of these as vertical. So, they may be indicated for very specific tumor types, and only specifically [indicated] for those. If they have certain toxicity to them, then you may need to use a G-CSF biosimilar or an ESA [erythropoiesis-stimulating agent] biosimilar to help with the toxicity on the bone marrow and the suppression of the person's ability to make white and red blood cells.
Another element to consider in this regard is the horizontal part. Biosimilar pegfilgrastim, for instance, it ends up being a very wide market. So, there is a great interest on the part of biosimilar manufacturers to have a pegfilgrastim because if you can position your product, you are cutting across a lot of tumor types and cutting across a lot of treatments. Whereas, if you think about, for instance, the biosimilar version of Herceptin [reference trastuzumab], that is very specifically for HER2+ [human epidermal growth factor receptor 2 positive] breast cancer. Breast cancer is the largest tumor type in the world, [especially in the] United States. You're still talking about a very narrow slice of a much wider tumor type.
Can you briefly explain the difference between how filgrastim biosimilars have fared on the US market vs pegfilgrastim biosimilars?
In the US market, the battle seems to be for pegfilgrastim [biosimilars] and part of that is convenience. You only have to administer it once [in a while]. So, there is a certain convenience to the patient after they have received a cycle of chemotherapy. Chemotherapy can be toxic and can be made prophylactic with pegfilgrastim. With biosimilar filgrastim, it is daily injections. For some reason in the United States, the preferences towards administering the pegfilgrastim at the cancer center. There is a little twist to that, and I'll get to that, as opposed to having a patient come back every day for up to 14 days technically—it would be usually they recommend about 11 days—and having that inconvenience.
Now, even with pegfilgrastim, technically any filgrastim product, should be administered between 24 and 72 hours following the end of chemotherapy administration. So, that really means that a patient would have to come back to the cancer center the next day to get their pegfilgrastim injection. The reality is, and it was accelerated by COVID-19 and studies have shown for several years, that both standard filgrastim and pegfilgrastim [should be administered] after chemotherapy has been administered, but on the [same] day as chemotherapy. There is increasingly more evidence that that is a relatively safe way of administering pegfilgrastim.
Also, we saw in the monitoring G-CSF study that we did in Europe is that a lot of clinicians are just administering 5 days of standard filgrastim. They just say, "I don't want to have to worry about my patients going neutropenic or febrile neutropenic. Let's just give them 5 days." In Europe, that's a lot easier [to do] because people live much closer together. There's home health nurses who can come and administer the medication, or you trust your patients and they can take it home, put it in the fridge, and every day, they, themselves or a family member, gives a patient a subcutaneous injection.
In the United States, the uptake of Zarxio started out well because it was the only thing available, and payers were realizing that they can save money here by using a biosimilar. And cancer centers were also saying, "We could save money by using the biosimilar." In the United States, it's predominantly pegfilgrastim biosimilars right now. Where standard filgrastim may still come in is in stem cell mobilization for stem cell transplants and pneumatological disorders, for instance.
What we have also seen, but it's never gotten huge traction, is that certain payers were not authorizing pegfilgrastim because pegfilgrastim originally was priced at 11 times more than daily filgrastim when when Amgen brought them on the market. So, the payers are saying, "No, we're not authorizing pegfilgrastim. We're authorizing 5 or 7 days of daily filgrastim." We saw them more in the major urban areas where it is easier to get to your local cancer center as opposed to living in Arizona, where it may take you 2 or 3 hours of driving or 4 or 5 hours of driving to get to your cancer center.