Skylar Jeremias is the Managing Editor for The Center for Biosimilars and The American Journal of Managed Care (AJMC).

Skylar Jeremias

As biosimilars continue to replace originator biologics across Europe, clinicians and payers are increasingly looking to real-world data to confirm that large-scale switching strategies do not compromise patient safety. 

 from Denmark suggest that serious safety events remained uncommon among people with inflammatory arthritis treated with the infliximab biosimilar GP1111, including those who underwent biosimilar-to-biosimilar switching.

New Danish registry data confirm the safety of switching to infliximab biosimilars, showing low rates of serious adverse events in patients with inflammatory arthritis. | Image credit: Ilya - stock.adobe.com

The observational cohort study evaluated safety outcomes in routine clinical care among people with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) who initiated GP1111 between April 2019 and April 2022. Investigators used data from DANBIO, Denmark’s nationwide rheumatology registry, linked with national hospital, prescription, and mortality registries to capture serious adverse events during the first year of treatment.

Although randomized controlled trials have shown comparable safety profiles between infliximab biosimilars and the originator product, evidence has been more limited for biosimilar-to-biosimilar switching, particularly in heterogeneous, real-world populations. Denmark’s national treatment guidelines have mandated several infliximab switches over the past decade, creating an opportunity to evaluate safety outcomes across multiple switching scenarios.

 The authors noted that lingering concerns around immunogenicity and rare adverse events have contributed to clinician and patient hesitancy, underscoring the need for high-quality registry data.

The analysis included 2132 adults who initiated GP1111 during the study period. Of these, 1534 individuals (72%) had switched from another infliximab biosimilar, most commonly CT-P13. Participants were stratified into 5 mutually exclusive subcohorts based on prior biologic disease-modifying antirheumatic drug (bDMARD) exposure, including originator-experienced biosimilar switchers, originator-naïve biosimilar switchers, infliximab-experienced users, infliximab-naïve but bDMARD-experienced users, and bDMARD-naïve users.

Across indications, the median age ranged from the mid-40s to early 60s, and median disease duration ranged from 6 to 11 years. Approximately 23% of patients had at least 1 comorbidity at baseline, and 14% had used oral corticosteroids in the year prior to starting GP1111. Disease remission at baseline varied by diagnosis, occurring in 55% of people with RA, 54% of those with PsA, and 30% of those with axSpA.

During the 1-year follow-up period, serious safety events were infrequent across the overall cohort. Age- and sex-adjusted incidence rates per 100 person-years were 1.0 or lower for major adverse cardiovascular events (MACEs), venous thromboembolic events (VTEs), death, and severe allergic reactions.

A total of 19 MACE events were observed, corresponding to an adjusted incidence rate of 1.0 per 100 person-years. These events primarily occurred among older individuals, with a median age of 66 years. Venous thromboembolic events were rare, with 11 events recorded and an adjusted incidence rate of 0.6 per 100 person-years. Nine deaths occurred during follow-up, yielding an adjusted incidence rate of 0.6 per 100 person-years.

Severe allergic reactions were also uncommon, with 16 events reported. Although these reactions were observed more frequently among infliximab-naïve but bDMARD-experienced individuals, the overall adjusted incidence rate remained below 1.0 per 100 person-years.

Serious infections represented the most frequently observed adverse outcome. Fifty-eight serious infections requiring hospitalization were identified, corresponding to an adjusted incidence rate of 3.2 per 100 person-years in the overall cohort. Rates varied across treatment history subgroups, ranging from 2.1 to 5.6 per 100 person-years. In multivariable analyses, a history of serious infection prior to GP1111 initiation was associated with a higher risk of subsequent serious infection (HR, 2.06; 95% CI, 1.19-3.57). Other baseline factors, including prior biologic treatment history, were not significantly associated with infection risk.

The authors concluded that GP1111 demonstrated a favorable safety profile during the first year of treatment, regardless of prior infliximab or biosimilar exposure. They noted that serious infection rates were comparable to those previously reported for originator tumor necrosis factor inhibitors in similar populations.

Several limitations were acknowledged. The observational design precluded causal inference, and the low number of events limited the ability to adjust for multiple covariates or conduct detailed subgroup analyses for rare outcomes. Additionally, follow-up was limited to 1 year, and findings may not reflect longer-term safety. Nevertheless, the use of nationwide registries with near-complete coverage strengthened the reliability of event capture.

1. Nabi H, Jensen KY, Westermann R, et al. Safety outcomes in 2132 Danish patients with inflammatory arthritis treated with biosimilar infliximab (GP1111) in routine care. 

. Published online December 23, 2025. doi:10.1177/1759720X251393114

2. Nabi H, Hendricks O, Jensen DV, et al. Infliximab biosimilar-to-biosimilar switching in patients with inflammatory rheumatic disease: clinical outcomes in real-world patients from the DANBIO registry. 

. 2022;8(2):e002560. doi:10.1136/rmdopen-2022-002560

Articles

New Danish registry data confirm the safety of switching to infliximab biosimilars, showing low rates of serious adverse events in patients with inflammatory arthritis.

Danish Registry Analysis Finds Consistent Safety After Switching to Infliximab Biosimilar GP1111

Chelsee Jensen, PharmD, BCPS, senior pharmacy specialist and pharmaceutical formulary manager at Mayo Clinic, shared her insights on future biosimilar development amidst recent FDA approvals and policy changes.

In an interview with The Center for Biosimilars

 (CFB), Jensen expanded on how recent changes in the biosimilar landscape might affect payers and patients.

Mayo Clinic’s Chelsee Jensen, PharmD, shares how FDA guidance, pricing pressures, and formulary strategy are shaping the next wave of biosimilars.

This transcript was lightly edited for clarity. 

CFB: Given that roughly 90% of biologics coming off‑patent may lack a biosimilar, what proactive strategies should health systems adopt now to safeguard patient access and cost containment?

 From a health system perspective, this is a really challenging area because, as costs stay high, reimbursement might not always cover that medication expense from a health system perspective. I think for health systems to keep providing care without taking on major losses, we need to have effective site-of-care management strategies in place and strong contracting skills. The most cost-effective strategy for health systems may be to join forces and advocate with manufacturers, nonprofits, and coalitions to develop biosimilars, especially where spending is high and competition is limited. 

Additionally, I do think incentives are needed to encourage biosimilar development and help lower the overall cost of health care. This could require financial support from the federal government and nonprofit organizations.

It is promising to see that there has been a recent legislative change and efforts aimed at reducing biosimilar development costs by limiting some of those comparative effectiveness studies, especially when that robust analytical data is there to support it. However, I think challenges will still remain, since it is still quoted that the cost to develop a biosimilar in the US ranges anywhere from $75 million up to $250 million.

I think we do have a way to go, from a health care system perspective; the best we can do is create those coalitions so we can try to incentivize the development of biosimilars in some of those vacant categories.

 simplifies analytical comparability and clinical bridging. Which specific elements do you think will most accelerate time-to-market for future biosimilars?

The advancement of analytical technologies that are able to detect those differences or similarities with greater accuracy, and when combined with expanded access to sensitive measurement tools, will enhance the reliability of that analytical data. This improvement is expected to diminish the reliance on those in human trials and therefore reduce or lower the development costs. By having these superior technologies, we should be able to see earlier submissions of biologic license applications (BLAs), potentially leading to expedited approvals and accelerated markets.

 of multiple denosumab biosimilars in a single year shows rapid market expansion. What lessons can be drawn from that experience for upcoming biosimilar launches in other high-revenue biologics?

The recent guidance update that removed the requirement for the comparative effectiveness switching studies to achieve interchangeability designations does mark significant progress and has positively impacted the denosumab category, likely encouraging greater adoption. I think this category is particularly noteworthy as well, because denosumab is predominantly a medical benefit drug, though there might be some pharmacy benefit coverage as well, and it mainly affects older adults, where we see more government-insured, Medicare, or Medicare Advantage payer populations.

Here at Mayo Clinic, we're really focused on learning how we can more effectively manage biosimilar switches and biosimilar adoption by utilizing our electronic health record tools and exploring ways to enhance category flexibility through the electronic health record moving forward; meaning, with the product we change, how can we rapidly incentivize and do proactive conversion? And when we do have that flexibility down the road, should the contract change while we're still under negotiation in this category?

I do suspect that most health care institutions may choose to contract with 1 manufacturer for both Prolia and Xgeva (denosumab; Amgen) biosimilars. However, because there's such strong competition in this category, it could be that we select one manufacturer for its Prolia biosimilar and another manufacturer for its Xgeva biosimilar, also in this category. It's not new, because Prolia and Xgeva have always shared the same Healthcare Common Procedure Coding System code. We are seeing that same trend with the biosimilars.

However, there’s still a need to keep a pulse on this, making sure that we're not running into any downstream billing errors and denials because of that shared fixed code. [We should continue] to rely on that provider education and how we build these on the electronic health record to make sure that we are selecting the appropriate product for the appropriate indication.

CFB: When several biosimilars compete for the same reference product, what criteria (clinical data, pricing, real-world evidence, patient-support programs) become most decisive for formulary placement at Mayo Clinic?

At Mayo Clinic, at this stage, we really have a high level of confidence in the clinical data coming from the process for a vast majority of the biosimilar assets. I think the final decision will likely depend on factors such as supply resiliency, manufacturer reputation, and history and pricing, because in the denosumab categories, specifically, this is a heavy government population, and I don't think co-pay assistance really plays a role here, as we know that many of our government programs are exempt from co-pay assistance for assistance programs.

However, other categories that are coming out, like omalizumab, Xolair biosimilars, natalizumab, and Tysabri biosimilars, do have a higher volume of commercially insured populations, and therefore copay assistance and payer coverage are some aspects that I do expect would be important considerations for those categories, but not really a focus for the denosumab category.

CFB: What early warning signals does Mayo Clinic monitor to anticipate a ‘biosimilar void’ for a specific reference product, and how do those signals shape your formulary strategy?

Where we're really pivoting here at Mayo Clinic is [finding] a more robust way to monitor the financial performance and outcomes of our whole drug portfolio. We really worked on internal tools to track our drug costs, our reimbursement, and broader financial trends more efficiently. That way, we can determine where we are having reimbursement issues, and we're able to dig in. Is this due to a denial or to a prior authorization issue that maybe we can update within the electronic health record, or [something to] discuss with our providers? Or is this because our reimbursement is simply not covering our costs? Therefore, is the average sales price far below what we have to purchase the drug at?

When we get into those later line agents, of course, we'll try to negotiate and try to get better pricing on the drug, but this is where we're really seeing that biosimilar void. I know we can't get any better pricing. I know this drug is off patent, and we don't have any competition coming. And that's really where we have to have some of those other harder discussions, saying, What else can we do in this category? Could we potentially start partnering with a coalition (eg, Cost Plus, Civvica) or some of our other coalitions to really incentivize the development of these drugs?

Lowering that development cost because of the greater good that we need this type of drug in the US market, and that's where we're going. Where I think this biosimilar void does factor in is if we're not seeing any competition. This is really where healthcare institutions may have to make difficult decisions to move these drugs out to 340B facilities, or if they're an orphan drug, disproportionate share hospitals, and that's where access really could get limited for patients, and that's really where I hope we don't have to go in the market. But I’m sure that is where some health care institutions currently are in decisions that they might be facing right now.

Mayo Clinic’s Chelsee Jensen, PharmD, discusses FDA policy changes, biosimilar development hurdles, denosumab lessons, and payer access strategies.

Q&A With Chelsee Jensen, PharmD: FDA Policy Shifts, Biosimilar Development Hurdles, and Market Access in 2026

In HER2-positive breast cancer, pertuzumab remains a cornerstone therapy, but its price has limited access in some markets, underscoring the need for biosimilar alternatives that can maintain clinical confidence while expanding affordability.

A new study confirms KM118, a proposed biosimilar to pertuzumab, shows pharmacokinetic similarity and safety, paving the way for affordable HER2-positive breast cancer treatments. | Image credit: Romolo Tavani - stock.adobe.com

KM118, a proposed biosimilar to reference pertuzumab (Perjeta; Genentech, Inc.), was evaluated in a phase 1 pharmacokinetic study designed to support regulatory approval in China.

 was conducted to determine whether KM118 demonstrated pharmacokinetic similarity to the reference product and to assess its safety, tolerability, and immunogenicity in healthy participants, key requirements under international biosimilar development guidelines.

The randomized, double-blind, single-center, parallel-group study enrolled 100 healthy adult men in China. Participants were randomly assigned in a 1:1 ratio to receive a single 420-mg intravenous dose of either KM118 or reference pertuzumab. This fixed dose reflected established pertuzumab dosing and aligned with prior pharmacokinetic research. Blood samples were collected through 84 days after administration to characterize drug exposure, whereas safety and immunogenicity were monitored throughout the study period.

All participants were male, with a mean age of approximately 32 years and a mean body mass index of 22.9 kg/m². Most participants identified as Han Chinese, with a small number from other ethnic backgrounds. Individuals with clinically significant medical conditions, prior monoclonal antibody exposure, or evidence of pre-existing anti-drug antibodies were excluded, ensuring a relatively homogeneous and healthy study population suitable for detecting pharmacokinetic differences.

The primary pharmacokinetic endpoint was the area under the concentration–time curve from time 0 to the last measurable concentration (AUC₀–t). Biosimilarity was prespecified as a 90% confidence interval for the geometric mean ratio between test and reference products falling within the standard equivalence range of 80% to 125%. Secondary endpoints included maximum concentration (Cmax), AUC extrapolated to infinity (AUC₀–∞), and additional pharmacokinetic parameters.

Results showed closely aligned pharmacokinetic profiles between KM118 and reference pertuzumab. The geometric mean AUC₀–t was 74,465.82 ng·h/mL in participants receiving KM118 and 69,097.83 ng·h/mL in those receiving reference pertuzumab. The geometric mean ratio for AUC₀–t was 107.07%, with a 90% confidence interval of 99.92% to 114.72%, meeting the predefined biosimilarity criteria. Similarly, the confidence intervals for Cmax and AUC₀–∞ also fell within the accepted equivalence range, supporting overall pharmacokinetic similarity between the products.

Safety findings were consistent with expectations for pertuzumab exposure in healthy individuals. Most adverse events were grade 1 or 2 in severity, and no serious adverse events or grade 3 or higher events were reported. The most frequently observed events included laboratory abnormalities such as elevated triglycerides or uric acid, along with diarrhea and upper respiratory tract infections. The incidence and pattern of adverse events were comparable between treatment groups, suggesting no new safety signals associated with the biosimilar candidate.

Immunogenicity analyses showed similar rates of anti-drug antibody development between the 2 groups. Approximately 28% of participants tested positive for antidrug antibodies at the final assessment, with comparable proportions in the KM118 and reference arms. Neutralizing antibodies were rare, detected in only 1 participant. Although participants who developed antibodies had somewhat lower drug exposure and shorter half-lives, these findings were consistent with prior pertuzumab studies and did not differ meaningfully by treatment group.

The authors noted several limitations relevant to interpretation and payer decision-making. The study population included only healthy male participants, which limited generalizability to women and to individuals with breast cancer who may have comorbidities or receive combination therapies. In addition, the phase 1 design focused on pharmacokinetics rather than clinical efficacy, necessitating confirmatory phase 3 trials in patients with HER2-positive breast cancer to establish therapeutic equivalence.

Overall, the findings demonstrated pharmacokinetic biosimilarity between KM118 and reference pertuzumab, with comparable safety and immunogenicity profiles in healthy adults. For managed care stakeholders, these results represented an early but important step toward expanding biosimilar competition in the HER2-targeted therapy space, with the potential to improve access and moderate oncology drug spending pending further clinical confirmation.

Jeremias S. FDA approves poherdy: first interchangeable biosimilar to Perjeta. The Center for Biosimilars

. November 18, 2025. Accessed January 28, 2026. 

https://www.centerforbiosimilars.com/view/fda-approves-poherdy-first-interchangeable-biosimilar-to-perjeta

Li Y, Wang Y, Yang C, Zhao N, Wang X. A phase I, randomized, double-blind, parallel, single-dose pharmacokinetic study to evaluate the biosimilarity of KM118 (proposed pertuzumab biosimilar) with reference pertuzumab (Perjeta) in healthy male subjects. 

. 2025;57(1):2523561. doi:10.1080/07853890.2025.2523561

A new study confirms KM118, a proposed biosimilar to pertuzumab, shows pharmacokinetic similarity and safety, paving the way for affordable HER2-positive breast cancer treatments.

Early Evidence Supports KM118 as a Biosimilar to Reference Pertuzumab

Stakeholders across the US health care system navigated a maturing biological market that reached a significant milestone of 90 total approvals by the end of 2025.

 This progress, detailed in a recent industry report from Samsung Bioepis, highlighted how the biosimilar sector moved beyond early-stage growth into a complex era of high market penetration and shifting financial incentives.

The US biosimilar market evolves with 90 approvals, significant price drops, and new PBM models enhancing access to cost-effective therapies. | Image Credit: © ipopba - stock.adobe.com

As of December 2025, the FDA had cleared biosimilars for 20 unique biological molecules, with 63 of those 90 approvals (70%) successfully reaching the commercial market. These launches led to substantial price reductions over time; on average, the average sales price for biosimilars decreased by 52% within 5 years of the initial class launch. In more mature therapeutic areas, these price reductions reached as high as 77%.

Market adoption patterns revealed a distinct divide between "fast" and "slow" uptake markets. Oncology, ophthalmology, and pegfilgrastim biosimilars were categorized as fast-uptake products, achieving an average market share of 81% within 5 years of launch. In contrast, sectors such as immunology, filgrastim, and insulin glargine saw much slower adoption, averaging only a 25% market share in the same timeframe. By the third quarter of 2025, specific molecules like bevacizumab and trastuzumab reached biosimilar market shares of 92% and 88%, respectively.

Despite these gains, the industry faced significant issues regarding traditional pharmacy benefit management (PBM) contracting. Historically, the PBM model favored high-wholesale acquisition cost (WAC), high-rebate products because those products contributed more heavily to the "rebate guarantees" that PBMs promised to self-funded employers. This structure created a "rebate trap" where a lower-cost biosimilar might have a lower net price than the reference biologic but was excluded from formularies because it did not provide the necessary rebate volume to satisfy aggregate contractual guarantees.

In 2026, however, the report pointed to a critical shift toward fiduciary and transparent PBM models. These emerging frameworks prioritized trend management and cost control over rebate maximization. Some PBMs introduced "rebate credits," which allowed the price difference between a reference product and a biosimilar to count as a "phantom credit" toward rebate guarantees, effectively removing a major barrier to biosimilar adoption.

Thomas Newcomer, vice president and head of US commercial operations at Samsung Bioepis, commented on these systemic changes in the report's press release: “As the US healthcare market enters 2026, stakeholders’ approaches to prescription drug pricing and management continue to evolve. Alongside established PBM contracting structures, new models emphasizing alternative pricing reimbursement, transparency, and a shift towards more fiduciary responsibility have emerged in response to changing market conditions.”

Specific therapeutic areas also faced unique challenges as 2026 began.

 In the ophthalmology space, although 4 aflibercept biosimilar products are awaiting clearance to launch, the reference product faces only 1 competitor offering a 12% WAC discount. Meanwhile, the immunology sector saw a proliferation of complex pricing strategies; while private label brands became common for adalimumab and ustekinumab, most ustekinumab manufacturers avoided the dual "high WAC/low WAC" strategy that characterized the adalimumab market in previous years.

Looking forward through 2026, the continued erosion of reference product dominance appeared likely as PBMs pledged fuller rebate pass-throughs by 2028 and more employers adopted biosimilar-first strategies.

 These shifts suggested that the primary challenge for the industry was no longer demonstrating clinical parity but rather aligning financial incentives to ensure that the most cost-effective therapies reached the patient.

Biosimilar approvals. The Center for Biosimilars

. Updated December 22, 2025. Accessed January 27, 2026. 

https://www.centerforbiosimilars.com/biosimilar-approvals

SAMSUNG BIOEPIS: Biosimilar market report 12th edition, Q1 2026. January 23, 2026. Accessed January 27, 2026.

Samsung Bioepis releases Q1 2026 US biosimilar market report. News release. Samsung Bioepis. January 23, 2026. Accessed January 27, 2026. 

https://www.samsungbioepis.com/en/newsroom/newsroomView.do?idx=531&currentPage=1

Jeremias S. Happy birthday adalimumab biosimilars: reflecting on the first year of US competition. The Center for Biosimilars. January 31, 2024. Accessed January 27, 2026. 

https://www.centerforbiosimilars.com/view/happy-birthday-adalimumab-biosimilars-reflecting-on-the-first-year-of-us-competition

The US biosimilar market evolves with 90 approvals, significant price drops, and new PBM models enhancing access to cost-effective therapies.

Milestone Approvals, Evolving PBM Models May Redefine the 2026 Biosimilar Landscape

At a moment when high drug prices continue straining families and the healthcare system, the US finally has a clear opportunity to turn scientific progress into real relief for millions of patients. The FDA’s 

 of reforms to streamline biosimilar development and modernize interchangeability is one of the most important steps yet—expanding access to safe, effective, more affordable biologic medicines. But realizing that potential now requires Congress to act. FDA has opened the door; policymakers must walk through it.

FDA. | Image Credit: wladimir1804 - stock.adobe.com

The US faces an escalating drug-pricing problem that could be addressed through the increased uptake of biosimilar therapies. Unfortunately the regulatory environment has historically choked off that opportunity, as evidenced by 

. Projections show that, while 118 biologics will lose patent protection between 2025 and 2034, only 12 of these medicines have biosimilars in development.

The FDA’s reforms address this growing crisis by bringing the regulatory framework closer to global best practices and advancing policies long championed by patients, providers, and biosimilar manufacturers. At its core, this effort reflects a basic scientific truth: biosimilar development should be guided by modern analytics, not outdated conventions.

The announcement included draft guidance reevaluating whether comparative efficacy studies (CES) are needed for approval, along with a commitment to finalize long overdue reforms to the “interchangeability” designation. Together, these steps could cut years from development timelines, reduce costs, and accelerate competition—a transformative combination for patients with chronic conditions such as arthritis, cancer, Crohn disease, psoriasis, and asthma.

Ending the Era of Unnecessary Clinical Trials

A central component of FDA’s action is its updated position on CES. For years, the science has been clear: biosimilarity can be demonstrated through advanced analytics and pharmacokinetic data. CES, by contrast, are “blunt tools” that add significant cost and time but little scientific value.

 reinforces this. When biosimilars encounter approval issues, they arise from analytical data, not CES. No biosimilar has ever failed a clinical study without also failing analytically. This makes sense. Biologics act like precise lock-and-key systems. Analytical testing accurately predicts safety and effectiveness, and strict manufacturing standards apply equally to biosimilars and reference products.

Eliminating unnecessary CES will have a significant impact. Analysts estimate that removing redundant clinical requirements can reduce development costs by tens of millions of dollars per product and shorten timelines by more than a year. Those savings are what enable more companies to enter the market, increase competition, and lower prices.

Interchangeability: A Statutory Problem Congress Must Solve

FDA also signaled plans to finalize guidance removing switching-study requirements for “interchangeable” biosimilars. Globally, all approved biosimilars are treated as interchangeable. The US remains an outlier, maintaining a separate legal category that confuses physicians, patients, and insurers. This is a statutory issue. FDA cannot solve it alone. Congress created the interchangeability designation, and only Congress can modernize it.

 offers a clear path forward. The bill would presume that an FDA-approved biosimilar is interchangeable with its reference product, eliminating unnecessary switching studies and aligning US policy with scientific consensus. This reform would help ensure lower-cost biosimilars can be substituted at the pharmacy counter, improving access across the country.

A Chance for the US to Lead—Not Lag Behind

Regulators worldwide have already updated their biosimilar policies to reflect modern science. With the FDA’s announcement, the US has a rare opportunity not just to catch up but to lead.

Streamlining development by eliminating CES will reduce costs and accelerate approvals. Reforming interchangeability will remove statutory friction that has never reflected scientific reality. Together, these changes would strengthen the biosimilar market, reduce drug spending, and increase access to life-changing treatments.

The combination of FDA leadership and Congressional action can finally unlock the full promise of biosimilars. Patients cannot wait another decade for affordable medicines that already exist. Congress should move quickly to modernize interchangeability, support science-based regulation, and ensure that policies match the enormous potential of this market.

The FDA has taken a major step. Now policymakers must finish the job. The US can improve patient outcomes, lower health care costs, and enhance American competitiveness—but only if we act now.

 is the executive director of the Biosimilars Council. He leads the policy team for the Association for Accessible Medicines.

FDA Draft Guidance on Biosimilars Is a Win for Patients; Now Congress Must Finish the Job

Biosimilar competition was associated with meaningful reductions in out-of-pocket spending for patients with Medicare coverage receiving clinician-administered biologics, according to a new analysis of national claims data.

 The findings suggested that, unlike trends seen in commercially insured populations, lower biologic prices following biosimilar entry were more likely to translate into direct savings for Medicare beneficiaries.

Biosimilar competition significantly reduces out-of-pocket costs for Medicare patients, enhancing affordability for biologic therapies and improving access. | Image credit: digicomphoto - stock.adobe.com

, evaluated changes in annual out-of-pocket spending among Medicare Advantage enrollees who received 1 of 7 biologic drugs that later faced biosimilar competition. The analysis included filgrastim, infliximab, epoetin alfa, pegfilgrastim, bevacizumab, rituximab, and trastuzumab, which first encountered biosimilar competitors between 2013 and 2019.

The study was conducted amid ongoing questions about whether biosimilar-related price reductions meaningfully benefit patients. 

 among commercially insured populations found that out-of-pocket costs did not consistently decline after biosimilar entry, largely because patient cost sharing is often based on negotiated reimbursement rates rather than drug prices.

 In contrast, Medicare reimbursement for clinician-administered biologics is closely tied to average sales prices, raising the possibility that biosimilar competition could more directly reduce patient spending.

Using Optum’s deidentified Clinformatics Data Mart Database, the investigators identified 273,774 patient-years from 2009 through 2022. Patients had a mean age of 76 years, 57.6% were female, and more than half received biologic therapies as part of cancer care. Nearly half of administrations occurred in outpatient clinics, and 13.0% of patient-years involved receipt of a biosimilar. Patients receiving low-income subsidies or who were dually eligible for Medicare and Medicaid were excluded because of their substantially lower cost-sharing requirements.

Across all 7 biologics, mean annual out-of-pocket spending declined after biosimilar competition began. In the composite analysis, adjusted mean annual spending decreased by $94, from $233 in the year before biosimilar entry to $165 by 4 years after competition. Declines were observed for each drug, although the magnitude varied. Rituximab was associated with the largest reduction, while filgrastim showed the smallest change.

The proportion of patient-years with zero out-of-pocket costs remained stable at approximately 41% before and after biosimilar entry, indicating that savings were concentrated among patients who already incurred cost sharing. Among patient-years with nonzero out-of-pocket spending, mean annual costs declined by $163 over the 4-year postcompetition period.

Reductions were most pronounced among patients who paid coinsurance or deductibles, whose cost sharing is directly tied to drug prices. In this group, mean annual out-of-pocket spending decreased by nearly $200 after biosimilar competition. By contrast, patients who paid only flat copayments did not experience significant changes in out-of-pocket costs, a finding consistent with the structure of fixed-fee cost sharing.

Sensitivity analyses showed that reductions in out-of-pocket spending occurred across most of the spending distribution, with the largest absolute decreases among patients with higher baseline costs. Trends in Medicare average sales prices mirrored these findings, with prices for originator biologics generally declining after biosimilar entry while biosimilar prices remained lower and continued to decrease over time.

The authors noted several limitations. Claims data did not capture manufacturer assistance programs, which may have led to overestimation of patient spending. The analysis was limited to Medicare Advantage enrollees and may not generalize to patients in traditional fee-for-service Medicare. Changes in plan design over time could also have influenced out-of-pocket costs independently of biosimilar competition. Additionally, the findings were specific to clinician-administered biologics and do not apply to pharmacy-dispensed biologics covered under Medicare Part D.

Overall, the results suggested that biosimilar competition was associated with lower out-of-pocket spending for Medicare patients, particularly for those whose cost sharing reflected drug prices. The findings highlighted the potential for timely biosimilar entry and sustained competition to improve affordability and access to biologic therapies for older adults.

Riegler JS, Kesselheim AS, Rome BN. Out-of-pocket spending for biologic drugs after biosimilar competition for Medicare patients. 

. 2026;9(1):e2554235. doi:10.1001/jamanetworkopen.2025.54235

. Updated December 22, 2025. Accessed January 21, 2026. 

Feng K, Russo M, Maini L, et al. Patient out-of-pocket costs for biologic drugs after biosimilar competition. 

. 2024;5(3):e235429. doi:10.1001/jamahealthforum.2023.5429

Biosimilar competition significantly reduces out-of-pocket costs for Medicare patients, enhancing affordability for biologic therapies and improving access.

Biosimilar Competition Linked to Lower Out-of-Pocket Costs for Medicare Patients

For people who rely on insulin every day, even small changes can carry outsized weight, a reality that has complicated efforts to expand use of lower-cost biosimilar insulins across health systems.

 More than a decade after biosimilar insulins entered the market, uptake has grown slowly, shaped not only by regulatory frameworks and pricing policies but also by the perceptions and experiences of those most directly affected by switching.

globe health | Image credit: C Malambo:peopleimages.com - stock.adobec.om

, sought to clarify how health care professionals, people treated with insulin, and health service administrators have viewed and experienced switches from reference insulin products to biosimilars, highlighting persistent gaps in evidence relevant to managed care decision-making.

Biosimilar insulins have been available since 2014 and are approved on the basis of rigorous comparability exercises demonstrating similar quality, efficacy, and safety to reference products. Regulators in Europe, the UK, and the US have stated that biosimilars should be treated as interchangeable with their reference products, yet policies governing substitution and switching vary widely across jurisdictions.

 Despite the potential for meaningful savings in publicly funded and private health care systems, concerns about safety, efficacy, delivery devices, and patient acceptance have continued to limit broader adoption.

 The authors undertook this scoping review to map existing literature on stakeholder perceptions and experiences of biosimilar insulin switching and to identify where evidence remains sparse.

Using a systematic search of PubMed, Web of Science, and CINAHL Ultimate, supplemented by grey literature searches and reference scanning, the authors identified 184 records, with 20 meeting inclusion criteria. Eligible sources included quantitative and qualitative research studies, reviews, guidance documents, and opinion pieces published in English since 2014. Stakeholders of interest were health care professionals (HCPs), health service administrators (HSAs), and people of any age treated with insulin. Findings were synthesized narratively using thematic analysis rather than pooled quantitative outcomes, reflecting the heterogeneity of the literature.

Across multiple studies, awareness of biosimilar principles among HCPs was generally high, particularly among pharmacists. However, practical experience with switching was limited; in one survey, 67% of HCPs reported no direct experience switching people to biosimilar insulins. Levels of concern varied by profession. Diabetologists and nurses expressed higher levels of concern than pharmacists, particularly regarding efficacy and safety when switching established patients. In some studies, up to 32% of physicians and more than half of nurses reported major concerns about efficacy when switching.

Insulin-specific issues distinguished biosimilars from other therapeutic classes. Differences in pen devices, availability of connected or half-unit pens, and varying injection forces were frequently cited as barriers. HCPs also raised concerns about workload associated with education and monitoring after a switch, as well as skepticism toward pharmacy-level substitution without prescriber involvement. Although most HCPs acknowledged regulatory assurances of comparability, questions about long-term safety data and multiple switches between biosimilars persisted.

Evidence on patient perspectives was notably limited, with only 3 primary research studies identified from the US, Canada, and Japan. In a US survey examining a hypothetical future switch, most respondents expressed neutral or positive views toward biosimilar insulin, with only a small minority stating they would definitely refuse a switch. People with type 1 diabetes were slightly more hesitant than those with type 2 diabetes. Concerns centered on perceived brand quality, satisfaction with current therapy, and fears of reduced efficacy or safety.

Real-world experience data were sparse but informative. A Japanese study of people with type 2 diabetes who switched from reference to biosimilar insulin glargine reported no meaningful changes in treatment satisfaction, glycemic control, or adverse events. Similarly, a Canadian analysis of a mandatory switching policy found that only 2.8% of people switched back to the reference product, suggesting general tolerability of the transition.

Guidance directed at HSAs emphasized the need for structured switching programs, including clear criteria, education plans, and processes for informed consent. Administrators expressed concerns about legal responsibility, potential nocebo effects, and the logistical challenges of selecting among multiple biosimilars. Importantly, one Canadian study found no increase in health care resource utilization following mandatory switching, addressing a common concern that switches might drive additional clinical visits or monitoring costs.

Cost considerations were central across stakeholder groups, particularly in publicly funded systems such as the UK, where modest price differences sometimes limited enthusiasm for switching. In contrast, in settings where people bore more out-of-pocket costs, lower prices were a stronger driver of acceptance, though some individuals associated lower cost with lower quality. Factors expected to facilitate switching included robust real-world evidence, consistent education for HCPs and patients, endorsement from professional bodies, and shared decision-making approaches that allowed for switching back if needed.

The analysis did not assess study quality or quantify effect sizes, and the included literature was heterogeneous in design and geography. The authors noted a striking lack of data on stakeholders who had direct experience with biosimilar insulin switching, particularly outside a few high-income countries. As they concluded, “almost no literature related to the experience of stakeholders who have already engaged in biosimilar insulin switching was identified,” underscoring the need for pragmatic, real-world research to inform managed care policies.

For payers and health systems considering broader biosimilar insulin adoption, the findings suggest that clinical equivalence alone is insufficient. Addressing education gaps, device-related concerns, and the lived experiences of people treated with insulin will be critical to translating theoretical savings into sustainable practice.

1. Switching or deprescribing insulins: when & how. Enclara Pharmacia. June 23, 2022. Accessed January 19, 2026. 

https://enclarapharmacia.com/palliative-pearls/switching-or-deprescribing-insulins-when-how

2. Jeremias S. From Amjevita to Zarxio: a decade of US biosimilar approvals. The Center for Biosimilars

. March 6, 2025. Accessed January 19, 2026. 

https://www.centerforbiosimilars.com/view/from-amjevita-to-zarxio-a-decade-of-us-biosimilar-approvals

3. Hindley B, Wright S, Ooi C, Da Costa R, Cope L. Exploring stakeholder perceptions and experience of biosimilar insulin switching: a scoping review. 

 2026;9(1):e70142. doi:10.1002/edm2.70142

4. Biosimilar medicines can be interchanged. EMA. September 19, 2022. Accessed January 19, 2026. 

https://www.ema.europa.eu/en/news/biosimilar-medicines-can-be-interchanged

5. Guidance on the licensing of biosimilar products. UK MHRA. Accessed January 19, 2026. 

https://www.gov.uk/government/publications/guidance-on-the-licensing-of-biosimilar-products/guidance-on-the-licensing-of-biosimilar-products

6. Jeremias S. A closer look at new FDA guidance removing barriers to biosimilar development. The Center for Biosimilars. October 30, 2025. Accessed January 19, 2026. 

https://www.centerforbiosimilars.com/view/a-closer-look-at-new-fda-guidance-removing-barriers-to-biosimilar-development

Explore the complexities of insulin biosimilars, their safety, and the impact on diabetes management in global health systems.

Perceptions Still Play a Central Role in Biosimilar Insulin Switching

As biosimilars move into broader therapeutic areas, osteoporosis has emerged as a key test case for demonstrating equivalence in both bone density outcomes and safety.

Denosumab biosimilars enhance treatment access for postmenopausal osteoporosis, demonstrating equivalent efficacy and safety to reference products in recent trials. | Image credit: Lamina - stock.adobe.com

With 9 and 10 pairs of denosumab biosimilars approved in the US and European Union, respectively, lower-cost biologic alternatives to Prolia and Xgeva (reference denosumab) are increasingly shaping treatment access in osteoporosis, where long-term adherence is essential to prevent fractures and downstream costs.

In a recent randomized phase 3 trial, investigators addressed persistent cost and access barriers associated with denosumab, a monoclonal antibody that inhibits receptor activator of nuclear factor-κB ligand (RANKL) and is widely used for fracture risk reduction.

 Although denosumab has demonstrated durable efficacy and an acceptable long-term benefit–risk profile, its biologic pricing has limited uptake in some settings. Biosimilars are intended to expand access while maintaining equivalent clinical performance, a requirement emphasized by both the FDA and the European Medicines Agency.

The multicenter, double-blind study enrolled women aged 60 to 90 years with postmenopausal osteoporosis across 76 sites in Europe and the US between 2021 and 2023. Participants were randomized 1:1 to receive either the proposed biosimilar RGB-14-P or reference denosumab at a dose of 60 mg administered subcutaneously every 6 months, with follow-up through 52 weeks. All participants also received daily calcium and vitamin D supplementation.

A total of 473 participants were randomized and treated (n = 242 assigned to RGB-14-P and 231 to reference denosumab), and more than 92% completed the 52-week main study period. At baseline, the mean age was 66.7 years, and nearly all participants were White. Mean lumbar spine bone mineral density (BMD) T-scores were approximately −3.0 in both groups, consistent with established osteoporosis. Around 10% of participants in each arm had experienced a fracture within the year prior to enrollment.

The trial included 2 co-primary end points designed to satisfy regulatory expectations for biosimilar equivalence: percentage change from baseline in lumbar spine BMD at week 52 and area under the effect curve for percentage change in serum C-terminal telopeptide of type 1 collagen (CTX) through week 26. Both end points met prespecified equivalence margins.

At week 52, the adjusted mean increase in lumbar spine BMD was 4.89% in the biosimilar group and 4.55% in the reference denosumab group, yielding an estimated between-group difference of 0.34 percentage points (95% CI, −0.40 to 1.09), well within the equivalence margin of ±1.45%. Analyses required by US regulators also demonstrated noninferiority and nonsuperiority of the biosimilar relative to the reference product.

Pharmacodynamic outcomes mirrored these findings. The geometric mean ratio for the CTX area-under-the-curve end point was 1.01 (95% CI, 0.98-1.05; 

 = .49), confirming equivalent suppression of bone resorption. Secondary efficacy end points, including changes in total hip and femoral neck BMD at weeks 26 and 52, did not differ significantly between treatment arms.

Fracture outcomes, although not powered as primary end points, were similar across groups. By week 52, vertebral fragility fractures occurred in 1.7% of participants receiving RGB-14-P and 3.5% of those receiving reference denosumab, while nonvertebral fragility fractures occurred in 1.7% and 4.3%, respectively. Investigators noted that the overall fracture incidence was low, a common limitation in osteoporosis trials of relatively short duration.

Immunogenicity rates were low and comparable. Binding antidrug antibodies were detected in fewer than 1% of participants in either group, and neutralizing antibodies were identified in 0.4% of participants in each arm. Safety profiles were also similar, with approximately two-thirds of participants in each group experiencing at least 1 treatment-emergent adverse event. The most commonly reported events included infections such as COVID-19 and nasopharyngitis, hypocalcemia, headache, and arthralgia. Serious adverse events were uncommon and balanced between groups.

Investigators emphasized that the findings align with regulatory standards for biosimilar development. They wrote that the biosimilar “demonstrated equivalent efficacy and pharmacodynamics and similar immunogenicity and safety” compared with reference denosumab, adding that the results support its ability to “replicate the therapeutic benefit” of the originator in clinical practice.

Several limitations were acknowledged. The study population lacked racial diversity, which may affect generalizability, and follow-up was limited to 1 year, precluding assessment of longer-term fracture outcomes. Additionally, low fracture event rates constrained conclusions regarding comparative fracture prevention, although BMD changes are an accepted surrogate end point for regulatory decision-making.

From a managed care perspective, the results add to a growing body of evidence supporting denosumab biosimilars as clinically comparable options that may reduce drug spending while preserving outcomes. If approved and priced competitively, RGB-14-P could provide payers and health systems with additional leverage to improve access and support sustained osteoporosis treatment adherence.

Biosimilars approvals. The Center for Biosimilars

. Updated December 22, 2025. Accessed January 15, 2026. 

Seefried L, Ferrari S, Páll D, et al. A randomised phase 3 study comparing the efficacy and safety of proposed denosumab biosimilar RGB-14-P and reference denosumab in women with postmenopausal osteoporosis. 

. 2025;36(12):2497-2507. doi:10.1007/s00198-025-07711-x

Denosumab biosimilars enhance treatment access for postmenopausal osteoporosis, demonstrating equivalent efficacy and safety to reference products in recent trials.

Trial Data Support Equivalence of Denosumab Biosimilar in Postmenopausal Osteoporosis

Tighter health care budgets have forced payers to scrutinize how high-cost biologic medicines are financed, particularly as use continues to expand across oncology and chronic inflammatory conditions. In Australia, a combination of pricing reforms and biosimilar entry has been positioned as a way to preserve access while curbing spending growth.

Australia's biosimilar adoption significantly reduces biologic medicine costs, enhancing access while maintaining utilization amid tighter health care budgets. | Image credit: Anton Balazh - stock.adobe.com

A recent analysis evaluated how the introduction of biosimilars affected spending, utilization, and pricing for several widely used biologic medicines within the Australian market. Investigators conducted the study to address a persistent evidence gap: despite years of biosimilar availability, there had been limited public data quantifying how biosimilars influenced reference product prices, overall market expenditure, and volume under Australia’s Pharmaceutical Benefits Scheme (PBS).

Current State of Biosimilars in Australia

Australia’s biosimilar landscape has evolved significantly over the past decade as policy makers, regulators, and industry stakeholders have sought to balance medicines’ affordability with clinical confidence and uptake.

 Regulatory approvals and pricing policies have expanded the number of biosimilars available on the Therapeutic Goods Administration’s (TGA) register and the PBS, but real-world adoption continues to lag behind other Organisation for Economic Cooperation and Development nations.

As of 2025, the TGA has approved a growing number of biosimilars across multiple therapeutic classes, including denosumab biosimilars (Stoboclo and Osenvelt), an aflibercept biosimilar (Eydenzelt), and the first natalizumab biosimilar (Tyruko).

 These approvals represent a broadening of competition into treatment areas such as osteoporosis, oncology supportive care, and neuroimmunology, beyond traditional anti-tumor necrosis factor agents.

To support uptake, the government and PBS have implemented biosimilar uptake drivers that encourage prescribers to initiate treatment with biosimilars in eligible, treatment-naïve patients.

 Prescribing administrative burdens have also been reduced by streamlining PBS authority requirements for biosimilar medicines, making them easier for clinicians to prescribe.

The researchers used Australian sales data from the IQVIA MIDAS database covering both hospital and retail channels from 2010 through 2020. The analysis focused on 4 monoclonal antibodies or Fc-fusion proteins—etanercept, infliximab, rituximab, and trastuzumab—that had at least 1 biosimilar listed on the PBS for a minimum of 12 months. Outcomes included changes in total and reference product expenditure, standardized unit (SU) volume, average SU price, and biosimilar market share before and after biosimilar entry.

Across the 4 biologics, biosimilar introduction was associated with substantial spending reductions. Twelve months after biosimilars entered the market, total expenditure for reference products declined by 38.3%, while combined spending on reference and biosimilar products fell by 33.8%, even as overall use increased modestly. The authors reported that total consumption across products grew by 4.9% during the same period, suggesting that lower prices did not restrict access.

The magnitude of savings varied by molecule. Reference product expenditure fell by 55.6% for rituximab, compared with 17.9% for infliximab. By the most recent 12-month period analyzed, biosimilars accounted for nearly one-quarter of total spending across the 4 medicines, ranging from 20% for trastuzumab to 28% for rituximab.

Differences were also observed in early uptake patterns. In the first year after biosimilar entry, market share remained low for etanercept (2.0%) and infliximab (2.3%), which were among the earliest biosimilars introduced in Australia. In contrast, rituximab and trastuzumab—with more recent biosimilar launches—reached first-year market shares of 32.5% and 14.8%, respectively. Over time, these disparities narrowed. In the most recent year of data, biosimilars represented approximately 26% to 39% of total unit volume across products.

Price erosion appeared to be a key driver of savings. Average SU prices for reference products declined by 30% to 40% following biosimilar entry. For rituximab and trastuzumab, biosimilar SU prices were roughly 40% lower than those of the reference products. The authors attributed these reductions to Australia’s statutory price cuts and price disclosure policies, which require manufacturers to report sales data and trigger subsidy adjustments when competition emerges.

The analysis relied on aggregate sales data rather than patient-level information, meaning it could not estimate how many people received each medicine or assess clinical outcomes. Standardized units also did not always correspond to administered doses, particularly for oncology products such as rituximab and trastuzumab, where vial sharing and chemotherapy preparation practices may underestimate actual patient exposure. Additionally, the PBS is a dynamic system, with evolving indications, formulary changes, and clinical guidelines that may have influenced utilization trends independently of biosimilar entry.

Australia's biosimilar adoption significantly reduces biologic medicine costs, enhancing access while maintaining utilization amid tighter health care budgets.