Peek behind the paper: cheaper but challenging biosimilars
In this feature, we take a peek behind the paper with study author Pinar Karaca-Mandic (University of Minnesota; MN, USA) to discuss the potential benefits biosimilars may confer, as well as the additional regulatory challenges associated with these drugs.
Biosimilars are near identical agents of biologic products, offering matched drug safety and efficacy and generating competition between drug producers, which can reduce drug costs. In 2019, we reported on the results of a new analysis, conducted by researchers from the University of Minnesota and Mayo Clinic (both MN, USA), suggesting that the cost savings offered by biosimilars are not always so uniform and substantial. Further, biosimilars are associated with a number of additional regulatory challenges and concerns.
In this feature, we take a peek behind the paper with study author Pinar Karaca-Mandic (University of Minnesota; MN, USA) to further discuss the benefits and challenges associated with biosimilars.
Please could you introduce yourself and your institution(s)?
I am the Academic Director of the Medical Industry Leadership Institute in the Department of Finance at the University of Minnesota’s Carlson School of Management (MN, USA). I also serve as an Associate Professor in the Department of Finance, as well as a health economist, at the Carlson School of Management. In addition, I am a Research Associate within the National Bureau of Economic Research (MA, USA).
...biologics have revolutionized the treatment of cancer as well as many other severe and chronic conditions; but those advances have come with exceptionally high prices."
My research focus falls at the intersection of diffusion of new medical technologies, responses to clinical evidence on safety and ineffectiveness by providers and other stakeholders, and the functioning of health insurance markets as an enabler to healthcare services and medical technologies.
What prompted you to conduct this research?
In recent years, biologics have revolutionized the treatment of cancer as well as many other severe and chronic conditions; however, those advances have come with exceptionally high prices. In the USA, the Biologics Price Competition and Innovation Act (BPCIA) was passed as part of the Affordable Care Act. The BPCIA created an abbreviated licensure pathway for biological products shown to be either ‘biosimilar’ to, or ‘interchangeable’ with, a US FDA-licensed biological product – i.e., the reference product. The goal of the BPCIA was to create a pathway for the creation of biosimilar products that would result in improved competition, reduced prices and greater access for consumers.
Biosimilars are expected to be less expensive alternatives to reference biologics. However, biologics are far more complex in molecular structure than conventional drugs, potentially making them more sensitive to differences in manufacturing. Therefore, safety concerns and sustained efficacy are both critical issues in further development of biosimilars. While the BPCIA laid out the legal and regulatory framework for biosimilars, the response in the USA to this regulatory policy has been slow; only after approximately 5 years of the BPCIA did the FDA approve the first biosimilar product, an oncology drug, on March 6 2015.
As future biosimilar cancer treatments are approved, our study can provide a model to inform and guide biosimilar policy and reimbursement, to improve cancer care and reduce its financial burden on patients and society."
Our paper, published in Health Affairs, is one part of our large-scale study funded by the American Cancer Society (GA, USA). Our broader study objectives, focusing on the launch of the first biosimilar, are to shed light on the uptake of biosimilars using real-world data, document total and out-of-pocket costs of biosimilars and reference biologics to examine the affordability implications of the biosimilars, and, finally, investigate adverse events associated with biosimilars and reference biologics.
Examining commercially insured Medicare Advantage and Medicare Fee-For-Service populations, our goals are to 1) inform policy makers, providers, clinical practice and payers on potential barriers to adoption of biosimilars, 2) identify how biosimilars can serve as affordable treatment options and reduce costs of cancer care, and 3) provide an evidence base to evaluate biosimilars’ safety. As future biosimilar cancer treatments are approved, our study can provide a model to inform and guide biosimilar policy and reimbursement, to improve cancer care and reduce its financial burden on patients and society.
What benefits could biosimilars offers over originator biological molecules?
It is primarily a financial benefit: biosimilars have the potential to serve as less expensive substitutes for reference biologic products, improving affordability and reducing unmet needs. As originator biologic manufacturers lose their ‘exclusivity’ – that is, their sole right to sell their drug with no competition – biosimilar entry represents an opportunity to provide more affordable and broader access to patients by making the marketplace more competitive.
...biosimilar entry represents an opportunity to provide more affordable and broader access to patients by making the marketplace more competitive."
Biosimilars were first introduced in the European markets in 2007 and have been sold at prices approximately 25–30% lower than their reference biologics. In the case of filgrastim, our study shows important price reductions in the US markets as well.
It is likely that biosimilar access and use will vary across the USA, geographically and by patient-, payer- and provider-level factors. In the USA, studies have reported large variations in underuse, overuse and misuse of treatments, suggesting that market entry of biosimilars has the potential to alter practice patterns and improve access in cases with unmet needs due to cost.
What are some of the challenges associated with employing real-world data sources, such as commercial and Medicare Advantage insurance plans data, and what limitations may these impose on the results of your study?
In most cases, the OptumLabs and Medicare claims data do not allow for identifying drugs used in the inpatient settings. Therefore, our project is limited to the use of biosimilars in the outpatient setting – such as physicians’ offices, clinics and outpatient hospitals.
An additional limitation is that we do not observe the patients’ cancer stage or grade at the time of diagnosis and treatment. This is an inherent limitation of employing claims data. Therefore, we carefully chose our clinical patient cohorts based on knowledge of cancer type, chemotherapy regimen, patient age and presence of other co-morbidities, but not cancer stage.
Finally, as in any observational study, it is not possible to completely rule out confounding, even with rich set controls. It could be that patients who use the biosimilars are different than those who do not, in ways unobserved to us.
...real-world data sources allow us to observe much larger and more diverse cohorts than any clinical study could."
On the other hand, real-world data sources allow us to observe much larger and more diverse cohorts than any clinical study could. As with anything in science, it’s a tradeoff – in this case, we get less detailed data, but much greater reach.
At its time of market approval, filgrastim-sndz was 31% cheaper compared with filgrastim, for commercially insured patients. However, in 2018, filgrastim-sndz was only 23% cheaper than filgrastim. What are some of the factors that may have contributed towards this depreciation in lower price?
As you note, the price difference between filgrastim and filgrastim-sndz has narrowed a bit for the commercially insured since filgrastim-sndz entered the market. The reasons for this are complicated, and we aren’t always able to explain or forecast how pharmaceutical prices will respond to different market conditions.
...prices decline the most when there are many manufacturers of a drug."
With that said, I think it’s not too surprising that the price differential has decreased over time. If you think about it, at the time the biosimilar entered the market, there was a lot of uncertainty about the effectiveness and side effect profile of the biosimilar versus the originator. Physicians, patients and payers in the USA had almost no experience with biosimilars at that time; the biosimilar may have had to enter the market at a big discount to make it worthwhile to switch. Over time however, as people gained experience with the biosimilar, it was perhaps no longer necessary to use such a discount to encourage individuals to use the biosimilar.
Previous research, concerning specialty drugs that came off patent, has observed that prices decline the most when there are many manufacturers of a drug. In other words, if there are only one or two generics on the market, prices don’t decline as much as they do when there are many generics on the market. It could also be the case that further price declines will be seen in the future, if more manufacturers introduce filgrastim biosimilars.
How do you see the use of biosimilars changing in the future?
In the future, biosimilars will likely constitute the new frontier in oncology, as well as in other therapeutic areas. For example, biosimilar versions of monoclonal antibodies for various cancer treatments have recently been introduced in Europe. Given that the BPCIA laid out the legal and regulatory pathway for biosimilars in the USA, these biosimilars will likely soon go through the FDA approval process in the USA too.
As of November 2019, there were 22 US FDA-approved biosimilars, but only nine have launched in US markets; several are still awaiting patent expiration of original, reference biologic drugs.
Future research should include further examination of biosimilars as they launch, and look at patient, provider and geographic-level factors associated with uptake, as well as the effect of reimbursement policies that encourage or discourage the use of less expensive drugs. These are some of the topics we are currently pursuing in ongoing work.
Karaca-Mandic reports no disclosures relevant to this piece.