Hillel P. Cohen, PhD, is executive director of scientific affairs at Sandoz, helping to explain the principles of biosimilars and biosimilar policies to the healthcare community, patient advocacy groups, and health authorities. He has published and given presentations in the areas of biosimilar education, switching, interchangeability, naming, and safety. Cohen led Sandoz in its efforts on the first biosimilar presentation (Zarxio) to an FDA advisory committee and participated in the Biosimilar User Fee Amendments of 2017 negotiations on behalf of industry. He is active in biosimilar trade associations and helped cofound the Biosimilars Forum, where he is currently cochair of the education committee. He is also a member of the education and regulatory committees of the Biosimilars Council, a division of the Association for Accessible Medicines.

Hillel P. Cohen, PhD

Patients see drug couponing as a way to lower or avoid cost sharing on brand-name prescription drugs. Payers view drug couponing as undercutting their pharmacy benefit design. Pharmaceutical companies see drug couponing as the key to greater sales, especially when they are in nonpreferred formulary positions (i.e., after generic competition is launched).

In a value-based pharmacy benefit design, the payer assigns medications that are highly effective, lower cost, or both to lower formulary tiers, to make them attractive to plan members. On the other hand, agents that are deemed to be of less value are placed in higher tiers, or even excluded from coverage. Simply, lower cost sharing means greater incentive to use and better sales for the industry. However, drug couponing, which is now ubiquitous, remove the patient incentive to use higher value drugs (and the disincentive to use lower value agents).

In the case of biosimilars versus originator medications, drug coupons offered by the manufacturer of Enbrel

, for example, actually make it less expensive for the patient to purchase the originator than the biosimilar, assuming a lower-copay biosimilar tier. That is, unless Sandoz, the maker of the approved etanercept biosimilar, matches Amgen’s couponing program. In that case, there would be incentive or disincentive for either product, from the patient’s perspective.

In dealing with couponing programs, payers have 3 options: (1) let things be and hope that if patients have little cost sharing perhaps adherence will improve overall, (2) ban the use of couponing by members (in other words, don’t allow network pharmacies to accept them), or (3) exclude from coverage any drug for which coupons are offered (this would be a lot of drugs today).

, couponing has boosted prescriptions for branded medications by greater than 60%. For the nation as a whole, every copayment coupon adds up to $120 million over the first 5 years after a generic drug is introduced. For the manufacturers of 85 medications that first faced generic competition between 2007 and 2010, couponing boosted spending anywhere from $700 million to $2.7 billion over a scenario in which couponing did not exist.

To preserve the value of biosimilars, payers will have to carefully mull their limited options. Excluding coverage of originator products that have copayment coupons may not be practical, because of the delicate situation regarding switching of biosimilars and lack of an interchangeable designation, especially for patients on established therapy. Banning the use of copayment coupons seems like a more reasonable option for payers, but one that may cost them members, particularly in today’s heated competitive market. 

Payers will have to carefully mull limited options.

Drug Couponing: Better or Worse for Biosimilars?

Stan R. Mehr

Rick Lozano is the Vice President of Biosimilars and Integrated Business Development for AmerisourceBergen. His responsibilities span across AmerisourceBergen, working with internal teams and manufacturer partners to create and manage innovative biosimilar and follow-on biologic manufacturer relationships. In addition to his leadership in biosimilars, Lozano leads the team connecting AmerisourceBergen’s manufacturer sourcing and commercialization capabilities across all types of products to expand existing manufacturer partnerships and forge new business development opportunities.

Rick Lozano

Christopher Mikson, MD, JD, is a partner in Mayer Brown's Washington, DC office, where he serves as leader of the firm’s FDA Regulatory practice and coleader of the healthcare practice. He focuses his practice on FDA regulatory matters and complex litigation and transactional matters in healthcare and the life sciences.

Christopher Mikson, MD, JD

As the coronavirus disease 2019 (COVID-19) pandemic spreads, it will continue to affect the biopharmaceutical industry. Biosimilars are no exception, and the effect on their uptake and adoption will be multifaceted. Here are several ways that biosimilars are most likely to be influenced by COVID-19:

Inaccessibility of healthcare providers (HCPs) and other medical decision-makers:

 currently, COVID-19 is setting the priorities for most HCPs and hospital decision-makers: take care of affected patients, navigate the evolving COVID-19 coverage and payment landscape, and maintain an adequate supply of beds and personal protective equipment. During this time, institutions may lack the bandwidth to continue to evaluate complex biosimilar-related decisions and may stick to the status quo, the reference product, or the existing preferred biosimilar product until the dust settles. This will slow down biosimilar uptake across the board. As providers defer to their status quo therapy options to avoid unnecessary disruption, uptake of the 8 therapeutic oncology biosimilars 

 in the United States so far may be particularly hard hit.

Repurposed contracting and promotional activities: 

although many regular account manager activities have been disrupted by social distancing measures, contracting can be conducted effectively via digital media. This is especially true for biosimilar manufacturers with existing relationships or customers interested in immediate cost-saving opportunities who are not yet preoccupied with managing COVID-19. Many financial decision-makers (pharmacy directors, medical directors) are postponing contracting discussions. Account managers can now focus on bringing accounts on board for biosimilars and leave “pull-through” sales activity for later. Also, manufacturers that are preparing to launch biosimilars during this quarter or the next may decide to postpone marketing or do a soft launch, which would entail supplying product, leveraging digital or nonpersonal channels, and contracting via tele-detailing. This could affect biosimilars such as Merck's trastuzumab and bevacizumab biosimilars, Ontruzant and SB8, respectively, which are lined up for launch over the next 2 quarters.

COVID-19 is causing a dramatic mismatch of supply and demand that manufacturers are struggling to forecast. On the supply side, manufacturing and supply chain processes in hubs such as China, India, and the United States are being disrupted due to global lockdowns. On the demand side, conflated factors make demand difficult to predict. On one hand, patients delay seeking treatment, particularly for less convenient administration methods such as infusions, which can lead to lower patient volume and overall demand. On the other hand, stockpiling and demand for subcutaneous or oral formulations may cause a spike in demand for certain products despite decreasing patient volume. In February 2020, the FDA 

 the first case of a shortage of a drug due to coronavirus. Although all manufacturers are working to mitigate the risk of supply shortages, biosimilar manufacturers that rely on facilities in Europe and Asia may be particularly at risk on the supply side (

Delays in biosimilar approvals and clinical trials: 

most clinical trials are likely to be delayed due to challenges managing protocols, deprioritization in favor of more immediate acute care needs, and patients’ inability to travel to appointments. Beyond the logistics and prioritization challenges, manufacturers run the risk of trial participants contracting the disease, which leads to 

 on how to manage clinical trials during the pandemic. All of the above-mentioned complicating factors are likely to undermine Prescription Drug User Fee Act/Biosimilar User Fee Amendments dates for biosimilars with approval decisions scheduled by the end of 2020 (

Increased budget pressure can accelerate postcrisis biosimilar usage: 

Without a doubt, the current situation is putting significant budget pressure on the health system, with many providers 

 copays, coinsurances, and out-of-pocket costs due to COVID-19. Although the broader impact on the economy and health system is still unclear, what is certain is that after the crisis, providers will actively look for ways to compensate for the extra expense they are incurring now, and it will be more important than ever for biosimilars to deliver on their promise to bring savings to the healthcare system. In the meantime, it will be important to monitor what manufacturers of reference products and biosimilars do to help support providers as this situation evolves.

There are additional aspects of the pandemic that will affect both biosimilars and reference products alike, such as ensuring safe supplies of medicine in patients’ homes as we all observe social distancing. Patients, either on their own or in consultation with their HCPs, may start to make adjustments to treatment regimens to allow for less time in the hospital or the clinic, especially when it comes to biologics that suppress their immunity, as also recommended by 

Such recommendations, along with the already limited infrastructure, overburdened healthcare system, and social distancing policies will create a very difficult environment for biologics and biosimilars businesses in the short and medium term. However, companies can think strategically about how to create opportunities from these difficult circumstances, such as leveraging virtual technology for contracting discussions, stressing cost savings with cash-strapped customers, and improving patient-support wraparound services. These will help them set the stage for success in a post—COVID-19 world.

At the end of the day, the priority for everyone right now is protecting health and safety. Although biosimilar adoption and evolution to new treatment paradigms may stall, we firmly believe that health and safety are foremost in mind for providers everywhere.

Christina Corridon, MPH, MBA, is a principal in ZS’s Boston office and leads the firm’s biosimilar vertical. Scott Kniaz, MBA, is a strategy insights and planning manager in ZS’s Washington, DC, office. Will Gatziolis, MBA, is an associate principal in ZS’s New York office. Ross Shahinian is a strategy insights and planning manager in ZS’s New York office. Sandeep Sangwan, MPharm, is a knowledge management consultant in ZS’s New Delhi office.  All are key leaders in the ZS biosimilar vertical.

The coronavirus disease 2019 (COVID-19) effect on the biosimilar industry will be deep and lasting, causing not just approval and launch delays but profound structural changes in how business is done.
 

COVID-19's Multifaceted Effect on Biosimilars

Scott Kniaz, MBA

Another study from Europe found that biosimilar etanercept was effective and well-tolerated in the majority of patients who switched from originator etanercept.

The study looked at Samsung Bioepis’ biosimilar, SB4, which is sold as Benepali in European countries. 

 have also found SB4 to work well for the majority of patients who switched from the originator etanercept, Enbrel. The anti-tumor necrosis factor (anti-TNF) inhibitor, is currently prescribed in the United States for rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriatic arthritis (PsA), ankylosing spondylitis, and plaque psoriasis.

An observational study conducted in Poland looked at patients being treated for RA, juvenile idiopathic arthritis, PsA, or ankylosing spondylitis, in which the originator etanercept replaced SB4.  

Etanercept was replaced with SB4 in 162 patients (Group 1), and in another 6 patients SB4 was the initial biologic used (Group 2). Efficacy and safety were assessed over a 6-month period.

The biosimilar was effective and well-tolerated in the majority of patients, however, for 24 patients in Group 1 (14.8%), returning to the originator was necessary due to loss of efficacy or adverse events.

Previous observational studies have found rates of discontinuing the biosimilar ranging from 2-14%. Specifically in this study:

9 patients experienced clinically confirmed loss of efficacy

9 patients reported subjective loss of efficacy

13 patients reported adverse events, the most common of which were headache and skin lesions.

Of the 24, returning to the originator reversed the loss of efficacy or resolved the adverse event. No adverse events were reported in the 6 patients for whom the biosimilar was the initial therapy (Group 2), and the biosimilar was effective in these patients.

The authors conclude that SB4 was effective and well-tolerated in most patients, but that further research is required to investigate the effects of switching patients between originators and biosimilars.

Felis-Giemza A, Chmurzy&#324;ska K, Na&#322;&#281;cz-Janik J, et al. Observational study of inflammatory arthritis treatment by etanercept originator switched to an etanercept biosimilar.

2019;57(5):257—263. doi:10.5114/reum.2019.89516.

The study follows others that have found that SB4 works well for the majority of patients who switched from the originator etanercept, Enbrel.

Another European Study Finds SB4 Tolerated by Most Patients

Peter Page

 that it has entered into a partnership agreement with Mylan to commercialize its proposed etanercept (Enbrel) biosimilar. The agreement authorizes Mylan to market the potential biosimilar in Europe, Australia, New Zealand, Latin America, Africa, and Asia.  

Etanercept is an anti—tumor necrosis factor (TNF) inhibitor indicated to treat rheumatoid arthritis (RA), plaque psoriasis, ankylosing spondylitis, and other autoimmune diseases. Enbrel generated $5.2 million in 

Vinita Gupta, CEO of Lupin commented on the collaboration, 

, “We are extremely pleased to announce this partnership as both Lupin and Mylan share a commitment to bring affordable and high-quality medicines to market, especially in areas of unmet need.” 

 that Mylan has developed with a pharmaceutical company to accelerate a biosimilar commercialization. In April 2018, Mylan entered a partnership with Fijifilm Kyowa Kirin Biologics to launch its adalimumab biosimilar, referencing Humira, in Europe. 

“The introduction of biosimilars is an important mechanism to help increase access to more affordable biologics treatments, and our industry-leading portfolio of 20 biosimilar products positions Mylan to be at the forefront of delivering those sales,” said Rajiv Malik, president of Mylan of the collaboration. 

The proposed etanercept biosimilar completed a phase 3 clinical trial in February 2018 with a successful outcome. The 52-week trial, which included more than 500 patients with RA in 11 countries, compared the efficacy and safety of the proposed biosimilar directly with the reference product. 

Under the terms of the agreement, Lupin will receive an upfront payment of $15 million as well as an equal share in net profits of the product. The potential biosimilar has been filed with the European Medicines Agency and Japanese regulatory 

, and is planned to be filed in other domains.  

Lupin recently announced that it has entered into a partnership agreement with Mylan to commercialize its proposed etanercept (Enbrel) biosimilar.

Lupin Partners With Mylan on Etanercept Biosimilar

Christine Potkul

Will Gatziolis, MBA

Accelerated entry of generic and biosimilar drugs into the US market, often facilitated by settlement agreements, has resulted in an estimated $422.9 billion in health care system savings, according to a recent comprehensive analysis.

 The research, conducted by the IQVIA Institute for Human Data Science on behalf of the Association for Accessible Medicines (AAM), examined the impact of these agreements on drug availability and cost containment.

“The ability for generic and biosimilar manufacturers to procompetitively settle with brand-name drug manufacturers creates significant savings and efficiencies and brings lower-cost medicines to patients years earlier,” said John Murphy III, president and CEO of AAM, in a statement.

 “Efforts to severely limit patent settlements will hurt patients, cost billions of dollars, and exacerbate industry sustainability concerns in the generic medicines marketplace.”

The study focused on molecules with first generic or biosimilar launches between 2014 and the third quarter of 2024.

 Researchers utilized the IQVIA SMART U.S. Launch and Regulatory Insights module to identify molecules and their initial launch dates. Litigation and settlement details were gathered from various sources, including the Ark Patent Intelligence Database, US Securities and Exchange Commission filings, company announcements, and court decisions. To determine the "would-have-been" generic entry date without a settlement, patent expiration information was cross-referenced using the Orange Book database, Purple Book database, FDA approval letters, and the Ark Patent Intelligence database.

Of the 288 molecules assessed, 84 had settlements that resulted in early or timely generic and biosimilar entry after 2013. The findings indicated a significant acceleration of market entry, with launches occurring an average 64 months (approximately 5 years) before the original patent expiry for molecules with settlements. Specifically, 29% of the studied molecules saw generic or biosimilar entry between 1 and 5 years prior to patent expiration, and an impressive 30% experienced entry 5 to 10 years ahead of schedule.

One example highlighted in the report was teriflunomide, a multiple sclerosis drug. A settlement reached in 2017 with multiple generic abbreviated new drug application filers led to the launch of generics a remarkable 11 years before its anticipated patent expiry. This early entry alone translated into substantial savings, with the health care system saving an estimated $1.1 billion in 2023.

Across all molecules studied, generics and biosimilars that entered the market early due to settlements accrued an average of $5.0 billion in savings per molecule. Interestingly, the analysis did not find a strong correlation between the magnitude of health care savings and how early generic or biosimilar entry occurred.

Although the study underscored the immense benefits of settlements, it also shed light on instances of delayed generic or biosimilar entry despite such agreements. Four molecules with settlements experienced launch delays, primarily attributed to protracted FDA approval timelines or supply shortages for complex products. For instance, drugs like Welchol (colesevelam), Integrilin (eptifibatide), Aggrastat (tirofiban), and Istodax (romidepsin) saw settlements accelerate potential generic entry, but regulatory hurdles or supply chain issues ultimately slowed their market introduction. This emphasizes that although patent disputes may be resolved, other factors can still impede the swift availability of affordable medicines.

The report's findings carry significant implications for the future of the biosimilar and generic industries. The consistent pattern of earlier market entry through settlement agreements suggests that these strategies will continue to be crucial in fostering competition and increasing drug accessibility. The substantial health care savings realized underscore the economic advantages of promoting such agreements. However, the report also highlighted the need for streamlined regulatory processes and proactive measures to address potential supply chain issues, particularly for complex generic and biosimilar products.

Moving forward, the AAM predicted that the industry, in collaboration with regulators, will likely focus on optimizing the interplay between legal settlements and efficient approval pathways to maximize the benefits of earlier generic and biosimilar market penetration, thereby enhancing affordability and access to essential medicines.

1. Assessment of the impact of settlements: analysis results. AAM. June 3, 2025. Accessed June 3, 2025. 

https://accessiblemeds.org/wp-content/uploads/2025/06/202506-AAM-Impact-of-Patent-Settlements-IQVIA-Study.pdf

2. Generic and biosimilar patent settlements save $423 billion. Press release. AAM; June 3, 2025. Accessed June 3, 2025.

Patent settlements accelerate the entry of generics and biosimilars, saving the health care system $422.9 billion and enhancing drug accessibility.

Billions in Health Care Savings Realized Through Early Generic, Biosimilar Settlements

Maggie L. Shaw

In autologous stem cell transplantation, 

 of peripheral blood stem cells (PBSCs) is crucial, and the use of granulocyte colony-stimulating factor (G-CSF) therapies plays a key role in ensuring success. Lower-cost biosimilar G-CSF agents may be a way to reduce the overall cost of treatment, and in a recent study in a single center in Singapore, researchers found that a biosimilar filgrastim, Pfizer’s Nivestim (sold in the US market as 

), was safe and noninferior to its reference, Neupogen, in mobilizing stem cells for autologous stem cell transplantation.

, all patients who underwent autologous stem cell transplantation between 2011 and 2016 were included in the retrospective cohort. Those treated up to March 2014 (n = 66) had received the reference filgrastim, while those treated afterward received the biosimilar (n = 65). Patient characteristics were similar with the exception of chemo-mobilization regimen.

The primary outcome of the study was the proportion of patients who had successful mobilization, which was defined as a harvest of at least 2&thinsp;×&thinsp;10

In the biosimilar group and the reference group, mobilization was successful in 96.9% and 97% of patients, respectively (

= .988). The authors noted that the number of CD34+ cells mobilized was higher in the biosimilar group, although the difference did not achieve statistical significance. Safety was also similar; the incidence and severity of adverse events were comparable between the groups, with headache, back pain, and bone pain being the most commonly reported.

Notably, the median length of hospital stay required for mobilization was significantly shorter in the biosimilar group (15 days) than in the reference group (17 days), and the duration of G-CSF use per mobilization was lower in the biosimilar group (9 days) than in the reference group (10 days).

Using the biosimilar also resulted in a significantly lower drug acquisition cost, at $533.40 in the biosimilar group versus $1261.90 in the reference group (

According to the authors, using the biosimilar to mobilize stem cells was both safe and noninferior to using the reference filgrastim, and results in a lower drug cost and a potentially shorter length of hospitalization.

Chew C, Ng HY. Efficacy and safety of Nivestim versus Neupogen for mobilization of peripheral blood stem cells for autologous stem cell transplantation [published online December 27, 2019]. 

Using the biosimilar resulted in a significantly lower drug acquisition cost, at $533.40 in the biosimilar group versus $1261.90 in the reference group.

Authors