That’s a very interesting question that you asked, because the rituximab biosimilar is very warranted and is here. The originator has come out with a new subcutaneous molecule, which probably is priced less than their own reference product in terms of [intravenous, IV]. So we are evaluating the patient convenience option first, because for the intravenous rituximab, the patient has to be in the office for about 6 to 8 hours, and the originator has another molecule that is subcutaneous, which actually could be given in 15 minutes.

The other part is, because the subcutaneous molecule is a fixed dose, it probably [average sales price, ASP] calculation-wise, may become less expensive to the healthcare system as a whole. So right now we are in a holding pattern to evaluate the time in motion, the characteristics of both molecules, and depending on what is best for the patient, depending on what improves the healthcare-related quality of life, and depending on which molecule is helping address Part B drug prices will help us make a decision. Unless and until we have the biosimilar molecule out, and it’s priced at a very competitive place, we will have to look into all of these aspects before we decide to switch over to the biosimilars.

Videos

Kashyap Patel, MD, discusses considerations for using biosimilar versus subcutaneous rituximab.

Kashyap Patel, MD: Preparing for Biosimilar Versus Subcutaneous Rituximab

I think biosimilar education is still needed to understand the regulatory difference between the originator product, which has to show in phase 3 trials that it's better or noninferior to another agent, and that it has efficacy and safety. The FDA approves initial drugs based on efficacy and safety. Biosimilars are approved with less clinical evidence because they're really mirroring the originator products, so it's highly technical in terms of the analytic variables that have to be satisfied for a biosimilar compared to an originator. As oncologists understand that process better, they'll become more comfortable with it.

Lee Schwartzberg, MD, FACP, The West Clinic, explains the kinds of education that oncology providers still need to feel comfortable with biosimilars. 

Lee Schwartzberg, MD, FACP: Biosimilar Education for Oncologists

With my particular trust, we’ve been using biosimilars, or best-value biologics, for nearly 3 years now. Within each transition, we’ve gained a lot of insight and knowledge from the last one. We’ve had a very positive experience from all of our uptakes.

I’m very lucky that the team that we have, especially the rheumatology department, is very forward-thinking in terms of encouraging uptake of biosimilars and using them for our patients. So we’ve had very positive experiences.

With the first switch that we did, that was an infliximab biosimilar, that went well. That was an [intravenous, IV] switch, so patients were informed when they came in to have their infusion.

The second switch that we did was for etanercept. This is a subcutaneous product; with a subcutaneous switch, there are other considerations you have to think of. Because it’s a drug delivered through home care services in the [United Kingdom, UK], you have to manage the home care services, so that was slightly trickier, but we had very positive experiences with transitioning our patients. We transitioned maybe 300 patients, so that was a big switch for us.

After etanercept came rituximab, which was again easier because it’s an IV switch, so there were less monitoring and negotiations with home care services. Patients were also told when they came in to have their infusions.

And last, the adalimumab, which has also been a big switch for us, and which has gone very well. That’s because we’ve had a vast experience with previous switches that we can always then use to plan how we would do this switch.  All in all, a very good experience with switching.

Kalveer Flora, MPharm, London North West University Healthcare National Health Service Trust, discusses her trust's extensive experience with switching patients to biosimilars. 

Kalveer Flora, MPharm: Experience With Switching to Biosimilars

I think it's fair to say that it has been very positive. You know, it was introduced not that long ago, less than half a year ago, and the uptake in less than a month was 90%. Not 19%, but 90%.

In effect, Humira, which was by far the biggest pharmaceutical on the Danish market, has been wiped out completely from Danish hospital shelves. You just can’t have Humira anywhere in Denmark anymore. Even though they offered a rebate on 78%, that was not enough to keep them on the market for 2019.

In accordance, the Danish tender system has gone to 2 products where they have offered a rebate of 86%. So on the one hand, you have uptake of 90%, and you have a rebate on 86%. Imagine what that would do not just for the public health, the health economy of the Danish healthcare sector, but also for the patients, because at the same time, since the product has become cheaper, more patients have gotten access to the product.

Peter Jørgensen, director of the Industrial Association for Generic and Biosimilar Medicines, Denmark, explains the Danish experience with biosimilar adalimumab.

Peter Jørgensen: The Danish Experience With Biosimilar Adalimumab

The issue is whether these biosimilars will achieve the goal of reducing prices in reducing healthcare costs. And in actual fact, data in Europe (again, they’re about 10 years ahead of us) suggest perhaps a 20% to 30% reduction in pricing when competitive by biosimilars are available in the marketplace.

We're too early to know whether we'll see that type of impact in the United States. If we do, even a 20% to 30% reduction in cost in a multibillion-dollar industry is a large amount of money, so it would be useful, but we don't know yet whether that will actually happen.

 this past year, looking at the early utilization of the hematopoietic growth factor biosimilars suggest maybe about a 10% reduction in price so far, but now we have 5 competitive hematopoietic growth factor biosimilars, we now have 4 trastuzumab or Herceptin biosimilars for breast cancer patients, so as we get multiple competitors in a class of agents, there should be more competition and hopefully a greater impact on price.

Gary Lyman, MD, MPH, of the Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance, discusses how biosimilars could impact the cost of care.

Gary Lyman, MD, MPH: How Biosimilars Will Impact Price

This year for us is very special because we have European elections. It's a time when the political agenda gets quite reset for another 5 years, so it's very important and for us, it's important that the parliament that will be elected in May and then the European Commission that will be formed then in the fall all have a strategic agenda for health. That's very important for us, but more importantly that they have a reserved place for biosimilars to play an important role in that agenda.

Two points: I think, in Europe, there's a big focus on reducing inequalities in access, and biosimilars are very obvious and readily available to contribute to meeting that objective, so I think we're calling on the institution this year [in a very] big [way] to to have that strategic inclusion of biosimilars in meeting their health objectives.

The other bit is more on the industrial side of things, where biosimilars were born here in Europe because of how the system was set up early on, their legal framework and everything, but we haven't fared very well in manufacturing capability and know-how; that really needs to be nurtured because the the needs are growing in Europe and elsewhere, and I think it's important that we nurture that for the long-term.

So 2 agendas: one more on the equity, creating greater equity, and the other more on the industrial policy side. So this is our big agenda for 2019.

Julie Maréchal-Jamil, director of biosimilars policy and science at Medicines for Europe, describes opportunities for biosimilars in the year ahead.
 

Julie Maréchal-Jamil: Opportunities for Biosimilars in 2019

Nurses have been explaining to the patient what biosimilars are—some of the basic education that they are like generics, they have undergone enormous amounts of safety and efficacy as well as pharmacokinetic studies. So they really alleviate any concerns and anxieties that the patients have when we switch patients over, or when we start any new patients on the biosimilars.

Kashyap Patel, MD, explains the role that nurses play in educating patients about biosimilars.

Kashyap Patel, MD: Nurses' Roles in Biosimilar Education

Recently FDA has changed its guidances on how companies can make communications about their drugs and devices. There [are] actually 2 separate categories: one is economic information, like, for example, is a drug cost effective or how does it say, reduce the length of hospitalization, what kind of money does that save. The other one goes into what kind of communications, what things that companies say that are consistent with the labeling of a product.

Both of these guidances essentially have slightly liberalized what companies can say by giving companies more guidance on what is permissible and what is impermissible. The healthcare economic one, in particular, companies really wanted to see because there have been 2 laws in the last 15 years where Congress asked FDA to do more in that area and give more guidance.

So that one is great now because now we know particularly prior to approval for example, that you can go and talk with payers and show more data about what has this product done in clinical trials.

James Shehan, JD, chair of regulatory practice at Lowenstein Sandler, LLP, discusses the implications of recent FDA guidance on medical product communications.

James Shehan, JD: FDA Guidance on Medical Product Communications

So the first biosimilar, in fact the only biosimilar in the United States, was approved nearly 2 years ago* and it was based, as I indicated, largely on the preclinical work and pharmacokinetic, pharmacodynamic data and healthy volunteers.

They did run 2 large phase 3 trials, but in patients with chronic kidney disease, not in cancer patients. So in actual fact, the only data on cancer patients with the epoetin alfa biosimilar is observational, not randomized controlled trial data.

Now, it turns out that there is this drug is also available in Europe, known as epoetin zeta. It's essentially the same molecule that’s been approved in Europe. There, they have done large phase 3 trials in patients with cancer showing noninferiority to the originator epoetin alfa. No safety concerns, no immunogenicity concerns.  

So the FDA was willing to accept the data from the same drug in Europe plus demonstration of safety and efficacy in advanced kidney failure patients in the United States and say “this should work the same for supporting patients with chemotherapy-induced anemia.”

That indication is not nearly as frequent as it used to be. A lot of concern was raised a few years ago, so the use of these agents as opposed to transfusions has fallen off in the United States, but nonetheless, to have competitive biosimilar versions to lower the prices of these drugs hopefully will work to the advantage of of patients in the overall healthcare system.

Gary Lyman, MD, MPH, of the Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance, discusses the role of the first FDA-approved biosimilar epoetin alfa in cancer care.

Gary Lyman, MD, MPH: Biosimilar Epoetin Alfa in Cancer Care

The biggest challenge with biosimilars now is that they're new. The regulatory process to get a biosimilar approved by the FDA is very different than the originator product, and so I think physicians have to get more comfortable with understanding how it was done.

The big difference is that they don't require a lot of large-scale phase 3 trials on the clinical level. It's really about showing that the molecule is is highly similar to the originator molecule, which of course, being biologicals, every batch is a little different anyway. Even in the originator molecule you see the same thing with biosimilars.

So the FDA concentrates on a host of technical factors to show that they're very similar and less on the clinical side. We might not have a clinical trial with a biosimilar for every single indication that the originator has, but the label will show the same indications. In fact, the labels come from the original, largely, so I think oncologists have to get comfortable with the idea that these drugs are really can be substituted in the new patient for the originator drug at a much lower cost.

That's the real value of a biosimilar: they cost less to be developed, and therefore, on the market, they are one of many solutions to reducing the total cost of cancer care, which we need to do; it's just unsustainable.

So I think as more drugs come out, as there's more education about what a biosimilar really is and how they can be used in your clinic effectively, we’ll see oncologists will become much more comfortable with it.

Lee Schwartzberg, MD, FACP, medical director and senior partner at The West Clinic, explains what he sees as the main challenges with incorporating biosimilars in the cancer clinic.

Interviews