Part 1: Ivo Abraham Talks About Biosimilar Pegfilgrastim Savings Amid COVID-19

Ivo Abraham, PhD, RN, a professor in the Department of Pharmacy Practice at University of Arizona Health Sciences, and a health care consultant with Matrix45, discusses recent studies that demonstrated savings for pegfilgrastim vs the on-body injector.

Transcript:

CfB: I'm Tony Hagen, senior editor for The Center for Biosimilars®. Today we're talking with Ivo Abraham, a professor with University of Arizona Health Sciences in the department of Pharmacy Practice. He's also a health care consultant with Matrix45, which he co-founded. Abraham was coauthor of 2 studies of pegfilgrastim biosimilar versus the on-body injector [OBI]. He and other investigators sought to measure the savings potential for patients with non-Hodgkin lymphoma and diffuse large B-cell lymphoma. Abraham said the study findings could be used as a bargaining chip to obtain bigger discounts from manufacturers.

When do you use pegfilgrastim, and for what reasons, and how often?

Abraham: It's a very common part of cancer treatment. You need to take into account that a lot of chemotherapy regimens are highly myelotoxic. They suppress the bone marrow, which means that we do not efficiently produce red blood cells and white blood cells anymore. White blood cells protect us from infection. So, if you have a patient who's being treated with a highly myelotoxic regimen, that patient is at risk for neutropenia. The drop in white blood cells exposes that patient to other risks of infection and febrile neutropenia, which usually leads to hospitalization. And there's also a very significant mortality rate. So, the great innovation—it was truly an innovation that Amgen did first with Neupogen, the precursor to Neulasta—then later on in 2002, I believe, with Neulasta—was really to stimulate the production of white blood cells, and it helps patients who receive a highly myelotoxic chemotherapy regimen with that drop in their white blood cells, in their neutrophils, so that they can go back up.

We have seen that over the years a very significant reduction in mortality, even without febrile neutropenia [FN] or severe neutropenia. And it's obviously indicated for patients who receive what we call highly myelotoxic FN—febrile neutropenia risk greater than 20%. There's also a middle category of 10% to 20% myelotoxic regimens, where if patients have a risk factor, the US guidelines, the European guidelines, will say those patients should be considered for prophylaxis with Neulasta, or similar products—growth factors. There’s a few in addition to biosimilars.

CfB: What is the difference in cost between pegfilgrastims? How much can you can you save with biosimilar products?

Abraham: Well, the absolute savings depends on a number of factors. First of all, if it is for CMS, for Medicare, predominantly, those costs are publicly posted. And that is the average sales price (ASP), as we call it. Also, don't forget that 45% of cancer patients are not over the age of 65. They’re younger than 65. So, they're more likely to be insured by commercial payers. So, the issue is what do the payer and the manufacturer negotiate? The payer may also be a pharmacy benefit manager. And those things we don't know. We have certain indicators, something called the WAC—the wholesale acquisition cost. The average wholesale price gives us an idea of what this might be, but this is before rebates, and discounts, and everything else that gets negotiated behind closed doors. Now, one element that is important to point out is that for Medicare—now we're talking about the average sales price, the ASP, which is issued on a quarterly basis—and it's a pretty complex calculation. But it has the benefit of taking into account all of the discounts and rebates and price reductions that are allowed or that are given by the manufacturer for their drug. That may be for your reference product. So, that may be Amgen, that may also be for the biosimilar product. The interesting part with the ASP is that it is eroding the price differential between biosimilars and the reference product. In fact, we were just calculating or checking on the Medicare website, the CMS website, what the new numbers are that have just been released. And now we're seeing that not 1, but actually 2 of the biosimilars, with the ASP, are now more expensive than the reference products. That is for, let's say, roughly 55% of the patients of that class. And so, that price differential is eroding. Where it is not eroding is of course, on the commercial side, which is very significant. Also, those prices tend to be higher than those that are negotiated by CMS.

CfB: Let’s go to your studies and the settings and why you decided to do them.

Abraham: Well, we have been working in this line of work for the past 11 years. Actually, we have been doing biosimilar work since 2008, 2009—originally in Europe. How did that come about? People that we used to work with on growth factors, also red blood cell growth factors, had been recruited by up-and-coming biosimilar companies, when the first ones came to Europe, which was about 10 years before the United States. So, we've been working with them from the very beginning. We did the early studies on price comparisons for the European G5 countries. You know, if you convert to biosimilar, from 100% down to 10%, how much savings will you generate? Now, let’s be honest. That's not rocket science. If one product is cheaper than the other one, we can show their savings and how these savings accrue. But we then started thinking—and now we're talking 2012—it’s nice to have these savings, but what do we believe should be done with those savings? And that's when we started looking at this notion of expanded access.

Think of your home budget. You're able to save something, so you now have some freely available cash. You could put that to some other use, and you will put it to some useful use. The argument that we were trying to make is, this is also the time that we're seeing very good and very expensive cancer treatments coming on the markets. Then biosimilar conversions provide a way to shrink our growth factor budget. We can take that money and reallocate it totally on a budget-neutral basis to a payer to provide more patients either with more growth factor, or especially, with expensive cancer treatments.

CfB: What did you learn from these studies?

Abraham: Several observations are important. First of all, and it's an observation or a question: To what extent are payers really thinking along those lines? We're picking up signals that they're saying, “Here's an interesting argument. Here is where we could also provide a service to some extent—we could change our plans in such a way that more patients would be eligible, with a lower co-pay threshold for certain of these treatments.” That's the first important element. The second important element is that we never really know what is negotiated behind closed doors. So, we have to create scenarios where we put it on a curve from 10% conversion to 100% conversion. We may also put it on cost curves and see how those curves interact. That issue, ultimately, is these calculations are not difficult to replicate. And it creates a bit of a framework, maybe a platform, so to speak, where also payers can start looking at, if we now go for this particular health plan that we have with this biosimilar, or reference product, we can go negotiate with Amgen and see how far they're willing to lower the price, which Amgen has been doing, Rightfully so. So, that is an important aspect. But what has really begun to surprise us in the last few months is this erosion of the differential between biosimilars and the reference products, with regard to pegfilgrastim. And that is important, because of 2 reasons: First of all, the way the negotiated prices and negotiated contracts will evolve. It's probably more like what we have seen in Europe and other parts of the world where you put in your bid with the United Kingdom, for instance, the National Health Service. In other countries with a totally single payer system, the government payer agency, so that it's no longer going to be the marketing strategy of, “Let me go out and capture hospitals and health systems and cancer centers who want my product.” That will still continue a little bit. But, how can I as a biosimilar manufacturer or as a reference product manufacturer go negotiate with certain groups and put 2-, 3-, maybe even 5-year contracts in place, and in that way, secure my markets, market position. You can take the findings on cost savings and how this can pay for additional care and use those as arguments to coax greater discounts from the manufacturers.

And for instance, it is known that Amgen and UnitedHealthcare negotiated a deal for Neulasta. And I think that is totally appropriate. Sometimes, the perspective is, it's us against them. But it's also us among each other, because here we are coming on the market, now, with our biosimilar pegfilgrastim. There is an aspect here of not all manufacturers competing against each other. And we need to take into account that, historically, the biosimilars came from small companies who then sold their biosimilars to the larger ones—Sandoz, Novartis, Pfizer—and the larger companies have really acquired molecules from smaller, almost mom-and-pop laboratories. I don't want to minimize it, but very small laboratories say “OK, let's try to create [a biosimilar].”

CfB: So the OBI fails occasionally, and that's a reason why a doctor might want to use a straightforward pegfilgrastim—biosimilar or reference product. So, how does it fail? And tell us about whether providers are aware of these issues.

Abraham: Well, the failure can be related to a number of factors. It can be device failure, or there have also been instances of a user failure. You have a restless night—you know, somehow it comes off, whatever. And let me preface it by saying that our focus on the on-body injector failure is not meant as a way of promoting biosimilars. In fact, the OBI injector is a phenomenal concept. And there are 2 elements here. First of all, it has to do with when should pegfilgrastim be administered, or the standard filgrastim. And historically, also, according to the label, it has to be done between 24 and 72 hours after the end of chemotherapy. Now, that works, if everybody lives close together, close to a cancer center. You could go in the next day to get your shot. Increasingly, and actually, the first major set of studies were done by [Howard A. Burris III], the issue of same-day administration of filgrastim, pegfilgrastim. Really, you're there for your cycle infusion, and at the end, everything is finished. At the end, when everything is finished, they also give you your pegfilgrastim. There are some physiological reasons why that should not be done. It may interfere with the formation of the cells, etc. So, the safe practice is, wait 24/28 hours. And then administer. On the other hand, there's also a lot of evidence that same-day administration with pegfilgrastim might be safe. And that is growing. So, that is one element that we need to take into account, this issue of same-day administration, which you know, is done also in part for patient convenience. Now, if you live in Manhattan, it's a cab ride to your cancer center. If you live in Arizona and you live in Yuma and you’re being treated in Tucson, that's several hours in the car. And these are patients who are already very sick, very fatigued. So, there’s the additional cost. Maybe you stay overnight. There's a lot of patient convenience aspects, and that's why the National Comprehensive Cancer Network (NCCN), in their guidelines, even in last year's, or maybe even the one the year before, have already started saying, or hinting, if it is for patient convenience, distance, etc, same-day administration, the framing might be OK. So, that's an important element that affects Neulasta, that affects any of the biosimilars.

The beauty of the OBI injector is, of course, you can go home and 27 hours later, or thereabouts, you will get your prophylaxis, which is very important, as we know. The failure rates kind of surprised us and the literature is very young in that regard. OBI failure ranges from 1.7% to 6.9%, thereabouts. Let’s say 2% to 7% reported failure rates. No doubt, the next generation [product] will be improved in that regard. But the consequence is that patients don't have that protection against their drop in neutrophils. They’re exposed to infection and face hospitalization. According to the Centers for Disease Control, it’s over $30,000 for hospitalization for neutropenia. And the death rates, which according to Dr Lyman from the Hutchinson center in Seattle, is around 37% to 38%; so, that's a very high mortality rate, which is preventable.

Now, another reason why we should be concerned about device failure is COVID-19, and ASCO and NCCN and some other groups have come out with the idea that we should reduce patients coming through the cancer center. You need to have protocols to reduce the traffic. We certainly want to keep patients out of emergency rooms, for obvious reasons in the COVID-19 era. So, their advice has been either do same day, or probably safer and better, use the OBI. But then, of course, we need to make sure that this is not a patient who is going to have a device that fails. What clinicians should do is really educate patients and their caregivers, whoever accompanies them to do the chemotherapy. But what are the signs the signs that things are not going well? And in that case, you need to act immediately. Call us. Patient education, counseling, and caregiver counseling become very important.

CfB: What kinds of things can you do to ensure that the OBI is going to work as hoped for?

Abraham: Well, it's like any appliance. It has failure rates. And I'm sure that the engineers at Amgen are working very diligently on that.

CfB: So, you feel that doctors generally are aware of these issues and take them into account and have full discussions with patients?

Abraham: Actually, I don't have data on that. But I'm part of some discussions with the Association for Community Cancer Centers, which provides care for two-thirds of the cancer patients in the United States. There is increasingly more attention to discussion, or facilitating discussion between clinicians, but also office staff—the finance office—about the biosimilar dialogue.

Part 2 will be available to watch after January 1, 2021.