To mark World Health Day we spoke with Ivo Abraham from the University of Arizona (AZ, USA) about the role that biosimilars play in expanding access to cancer treatments, particularly in regards to the biosimilar filgrastim-sndz. If you would like to find out more about this study, make sure to read the full paper in Future Oncology.
Could you give us an overview of your study exploring the biosimilar filgrastim-sndz?
We had previously done a study for Europe as well as for the US on savings that can be generated by converting patients from the originator product to the biosimilar versions, as we had done earlier for the EU G5 countries (Germany, France, UK, Italy, Spain) for epoetin-alfa and filgrastim.
Savings can be pretty significant so what we tried to do in the paper for Future Oncology was to estimate savings for a payer or an insurer panel of 20,000 patients covered.
These were assumed to be patients who require filgrastim because they are getting myelotoxic chemotherapy and are at risk of chemotherapy-induced neutropenia or febrile neutropenia.
Let’s say we convert those from being treated either with daily filgrastim injections or with a single injection of pegfilgrastim, the pegylated version. What would be the savings? What can we do with those savings? Most payers would just put it back in the general account. However, using these savings, a payer can also, on a budget neutral basis, treat more patients with for instance some of the new and very expensive cancer therapies.
If we were to convert 20,000 patients who would be treated with filgrastim or pegfilgrastim to prophylaxis with biosimilar filgrastim, the savings would be enormous – in the article we report that savings could be between 6 and 59 million US dollars, depending upon how you calculate it and depending on how long the regimens are, especially the regimens with daily filgrastim. We then tried to estimate how many more patients with relapsing or refractory follicular lymphoma could be treated with a very expensive and relatively new drug, obinutuzumab. Depending upon how many savings are achieved, this would be between 52–544 patients.
We also estimated the number of patients with metastatic lung cancer who could be treated on a budget-neutral basis with pembrolizumab, a drug that is even more expensive than obinutuzumab. Depending on the savings, this came to between 18–192 patients. So, without it costing you as a payer anything more, the savings that come from converting to biosimilar filgrastim enable a lot of patients to receive antineoplastic treatment.
What advantages do biosimilars have over reference products?
One major advantage is that they’re just as efficacious and just as safe as the reference product. A second advantage is that they cost less. Basically, you are buying the same efficacy and the same safety at the lower cost. I should specify, however, that this is for biosimilars that are approved by either the EMA or the FDA or the regulatory agencies in countries that follow the EMA and the FDA. There are biosimilars made in less regulated markets but the quality of those biosimilars in terms of physico-chemical characteristics as well as efficacy and safety are often compromised.
In what ways could biosimilars such as filgrastim-sndz improve access to cancer medicines?
That was the focus of the exercise that we did (see above). Just as much as converting to biosimilars improves access to therapeutic cancer agents such as obinutuzumab and pembrolizumab, it can also help more patients get prophylaxis to reduce the likelihood of getting chemotherapy induced neutropenia or febrile neutropenia.
This also happens to be a time when prophylaxis patterns are changing. The original pattern of prophylaxis with filgrastim was approximately 11 daily injections. We demonstrated in the MONITOR-GCSF study, which was sponsored by Sandoz, the biosimilar subsidiary of Novartis, that today cancer clinicians have so much clinical experience with filgrastim that they are not following the guidelines about who to prophylactic and who not. Instead, clinicians are prophylacting on a pretty broad basis, including lower risk patients, for a few days not for 11–14 days, just to be on the safe side. In the MONITOR-GCSF study, the median was 5 days. Prophylaxis decisions today seem less driven by risk level, guidelines, or recommended duration.
What do you think are the biggest challenges in the widespread adoption of biosimilars and how can we overcome these?
Here we need to differentiate between Europe and the US because Europe has 10 years of commercial experience with biosimilars compared with appoximately 2 years for the US.
Clinicians in Europe are a lot more comfortable with biosimilars. Moreover, clinicians in Europe operate under single payer systems where a single payer decides what is going to be available, what they are going to buy and what they will pay for. In addition, there are other schemes that push biosimilar adoption.
We are going to see the same in the US as we have seen with generics. Thirty years ago physicians would say generics are inferior, but now the majority of drugs dispensed are generics.
In the US the adoption of biosimilars is going very slowly. One factor is physician reluctance; we saw that in Europe as well in the beginning. Fear mongering by the manufacturers of the originator drug is common, as it was in Europe. Physicians are rather uncritical and seem to readily adopt fear mongering messages. They are also rather uninformed about the preclinical and clinical requirements to get a biosimilar approved. They seem to forget that, for instance, the epoetin alfa that came out roughly 20 years ago is different from the one produced now. One could almost say that today’s epoetin alfa is a biosimilar of the original product. They also seem to forget that there is lot to lot variability in any biological agent, whether originator or reference. Add to this concern about the fact that biosimilars do not require Phase II trials as the therapeutic dose is known from the originator product.
In the US, drug manufacturers set an official price, but are allowed to give incentives and thus reduce the actual price paid. If a manufacturer engineers the incentive plans well, the official price of an originator product might get into the range of biosimilars. By the time a product goes off-patent and biosimilars enter the market, the originator product has long paid for itself. There is little if any additional research and development to be done. So, manufacturers of originator products may say “I’d rather sell my drug at 72% of the price, than lose market share and not get any income”. The issue of incentives got quite a bit of attention recently when Scott Gottlieb, the head of the FDA, commented that this “rigged payment scheme” impacts negatively on the adoption of biosimilars in the US.
A final point as to overcoming the barriers is independent media attention to biosimilars in both the general media and specialty publications.
What do you think could be the timeframe for widespread adoption of biosimilars?
Ask the payers!
Payers have been the major driver in the adoption of biosimilars in Europe, the Middle East and the Far East. In addition, purchasers and payers in these regions often use tenders to purchase drugs. Whoever puts in the most credible (but not necessarily the lowest) bid will get the contract. Tender-based purchasing is a major factor to accelerate adoption. More generally the biosimilar manufacturers are beginning to realize that they do not need to market their products in the old detailing model but instead adopt an educational model using medical science liaisons. The negotiating is with those who manage the care, meaning the payers.
In the US, it will also be important to engage the two large federal public payers, the Veterans Administration (which can negotiate drug prices) and Medicare (which cannot negotiate drug prices). These two payers should be early adopters of biosimilars.
Ivo Abraham, an outcomes and effectiveness researcher by trade, is Professor of Pharmacy and Medicine at the University of Arizona (Tucson, AZ, USA); where he is also affiliated with the Center for Health Outcomes and PharmacoEconomic Research, the Arizona Cancer Center, and the Center for Applied Genomics and Genetic Medicine. He has served as regular or visiting professor at universities in the US, Europe, and Asia. A native of Belgium, he received his BS from the Catholic University of Leuven, and his MS and PhD (clinical research) from the University of Michigan. His research program has been funded continuously since 1984 by governmental agencies, foundations, and corporations worldwide. He has served in the US as appointed and ad hoc reviewer for the NIH, the NIMH, the AHRQ, and the Veterans Administration; in Europe for the EU FP7 and HORIZON2020 funding programs; and in Canada, Japan, The Netherlands, Ireland, and Catalunya (Spain) for national funding agencies. He has been working as expert advisor to the Innovative Medicines Initiative, a joint € 5.3 billion (US$ 6.3 billion) undertaking of the European Union and the biopharmaceutical industry to stimulate innovation in human therapeutics since the Initiative’s inception in 2008. He currently serves as the Associate Editor for Quantitative Methods for JAMA Dermatology. He has (co-)authored 350+ articles, 75+ chapters, and 30+ books and monographs. His educational and scientific honors and awards include an Invitational Research Fellowship from the Japan Society for the Promotion of Science (2007-2008), which he conducted at Hyogo University and Aomori University.’)