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

Skylar Jeremias

For people with advanced hepatocellular carcinoma whose disease has progressed despite prior immunotherapy, treatment options have remained limited and largely empirical. New findings from the 

suggested that integrating stereotactic body radiotherapy (SBRT) with continued immune checkpoint inhibition and a bevacizumab biosimilar may offer a strategy to overcome resistance while maintaining an acceptable safety profile.

A phase 2 trial found that combining targeted radiotherapy with PD-1 blockade and a bevacizumab biosimilar generated meaningful responses in people with advanced liver cancer whose disease had progressed on prior immunotherapy. | Image credit: natali_mis - stock.adobe.com

The open-label, single-arm ReUNION-1 study, published in Nature Communications, evaluated SBRT followed by sintilimab (a PD-1 inhibitor) plus a bevacizumab biosimilar in people with unresectable hepatocellular carcinoma (HCC) whose disease had progressed after at least one prior anti–PD-1–based regimen. Immune checkpoint inhibitor resistance remains a substantial challenge in HCC, where objective response rates to monotherapy have historically ranged from 13% to 20%, and where second-line standards have largely been extrapolated from sorafenib-pretreated populations.

Between March 2022 and April 2024, investigators screened 25 patients and enrolled 21. All participants were included in the intention-to-treat analysis. The median age was 55 years, and 81.0% were men. All patients had Child-Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of 0 or 1. Chronic hepatitis B virus infection was the predominant underlying liver disease (85.7%). Most patients (61.9%) had received one prior line of systemic therapy, and 71.5% had extrahepatic metastases. Nearly all had previously received a tyrosine kinase inhibitor plus a PD-1 inhibitor combination.

Patients underwent SBRT (median dose 8 Gy per fraction for 5 fractions) directed at a selected lesion, followed by sintilimab 200 mg and bevacizumab biosimilar 15 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) in nonirradiated lesions per RECIST v1.1 criteria.

At a median follow-up of 9.1 months, the ORR in nonirradiated lesions was 33.3%, with 7 of 21 patients achieving a confirmed partial response. Stable disease was observed in 7 additional patients, resulting in a disease control rate (DCR) of 66.7%. Notably, irradiated lesions demonstrated a 100% local-regional control rate, and 76.2% achieved an objective response within the treated field. Durable disease control lasting at least 6 months was observed among patients with partial response or prolonged stable disease.

Median progression-free survival (PFS) was 6.2 months (95% CI, 3.7-15.1), with 6- and 12-month PFS rates of 57.1% and 14.3%, respectively. The estimated median overall survival (OS) was 24.4 months (95% CI, 9.2 months–not reached). Eight deaths had occurred at data cutoff.

Treatment-related adverse events (TRAEs) of any grade occurred in 81.0% of patients. Grade 3 or higher TRAEs were reported in 33.3%, including decreased platelet count, neutropenia, and gastrointestinal hemorrhage. Two grade 4 gastrointestinal hemorrhages were managed with endoscopic intervention, and 1 patient experienced grade 3 anaphylaxis requiring discontinuation of sintilimab. No treatment-related deaths were reported, and 14.3% discontinued therapy due to serious TRAEs.

The study also incorporated serial proteomic and immune profiling analyses. Responders had lower baseline interferon-γ (IFN-γ) levels and higher IL-6 and TNF-α levels compared with nonresponders. Lower baseline IFN-γ levels were associated with longer PFS and OS; patients with low IFN-γ had a median OS of 24.4 months compared with 9.3 months in those with high IFN-γ (HR, 4.12; 95% CI, 1.36-12.46). SBRT was associated with increased circulating IL-6, IL-15, and CD70 levels and decreased VEGFA levels, suggesting immune modulation that may have contributed to renewed sensitivity to PD-1 blockade.

The investigators acknowledged several limitations, including the small sample size, single-arm design, and enrollment at a limited number of centers in China, where hepatitis B–related HCC predominates. The relatively short follow-up period and lack of a comparator arm limited definitive conclusions regarding survival benefit. In addition, prior treatment heterogeneity may have influenced outcomes.

For managed care stakeholders monitoring the evolving biosimilar landscape, the use of a bevacizumab biosimilar in combination with immunotherapy and radiotherapy demonstrated feasibility in a heavily pretreated population. Although confirmatory randomized trials are needed, the findings suggested that combining locoregional and systemic approaches may represent a viable strategy for people with HCC whose disease has progressed on prior PD-1–based therapy.

1. Tang J, Yang Y, Liu D, et al. Stereotactic body radiotherapy with sintilimab and bevacizumab biosimilar in anti-PD-1 refractory hepatocellular carcinoma: the ReUNION-1 phase 2 trial. 

. 2025;17(1):823. doi:10.1038/s41467-025-67528-4

2. Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. 

. 2022;1(8):EVIDoa2100070. doi:10.1056/EVIDoa2100070

3. Qin S, Kudo M, Meyer T, et al. Tislelizumab vs Sorafenib as first-line treatment for unresectable hepatocellular carcinoma: a phase 3 randomized clinical trial. 

. 2023;9(12):1651-1659. doi:10.1001/jamaoncol.2023.4003

Articles

A phase 2 trial showed that combining targeted radiotherapy with PD-1 blockade and a bevacizumab biosimilar can elicit responses in advanced liver cancer.

Biosimilar-Backed Triplet Regimen Shows Feasibility in Heavily Pretreated Liver Cancer

More than €787 million was spent on omalizumab across 23 European countries in 2024 alone, underscoring the fiscal pressure associated with biologic treatment of severe allergic diseases.

 projected that the introduction of an omalizumab biosimilar could generate substantial savings for public payers over the next 5 years, with the potential to expand access to tens of thousands of additional patients.

Budget impact analysis finds omalizumab biosimilars in Europe could cut payer costs by €641M in 5 years, expanding access and driving major omalizumab savings. | Image credit: vadish - stock.adobe.com

Omalizumab, marketed as Xolair, is indicated for individuals with severe persistent allergic asthma, chronic spontaneous urticaria (CSU), and chronic rhinosinusitis with nasal polyps (CRSwNP). Although results from clinical trials have demonstrated reductions in exacerbations and improvements in quality of life, acquisition costs remain high. In the UK, annual treatment costs have ranged from £1664 to £26,624 depending on weight-based dosing.

 Across Europe, access has been constrained in some countries because of reimbursement restrictions and cost-effectiveness concerns.

To estimate the financial implications of biosimilar entry following patent expiry in September 2025, investigators developed a 5-year budget impact model from the payer perspective. The model compared a “world without biosimilars,” in which only originator omalizumab was available, with a “world with biosimilars,” in which a lower-cost biosimilar gradually captured market share. Twenty-three countries were included: Austria, Belgium, Bulgaria, Croatia, the Czech Republic, Finland, France, Germany, Greece, Hungary, Italy, Latvia, Lithuania, Luxembourg, Norway, Poland, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, and the UK. Countries were selected based on formulary listing, publicly available pricing, and IQVIA volume data.

Drug acquisition costs were derived from national list prices. The base-case analysis assumed that the biosimilar would enter the market at a 30% discount relative to the originator and that originator pricing would remain static—an assumption the authors noted likely underestimated real-world savings, as price erosion commonly occurs after biosimilar entry. Biosimilar uptake was modeled using adalimumab biosimilar adoption as a proxy, and omalizumab volume growth was extrapolated using historical compound annual growth rates between 2021 and 2024.

Under the 30% discount scenario, the model projected first-year savings of approximately €40 million across the 23 countries. Over 5 years, cumulative savings were estimated at €641 million. Germany was projected to realize the largest absolute savings—up to €130 million over 5 years—reflecting higher baseline utilization and spending. In contrast, countries with smaller populations or slower anticipated uptake, such as Luxembourg and Bulgaria, were projected to experience comparatively modest savings.

Investigators translated projected savings into potential access gains. Based on weighted average annual treatment costs across indications—48.37% for CSU, 44.77% for severe allergic asthma, and 6.86% for CRSwNP—the €641 million in cumulative savings could enable treatment of an estimated 96,491 additional patients over 5 years, assuming a full year of therapy per patient.

Sensitivity analyses examined deeper discount scenarios. At a 50% discount, cumulative 5-year savings were projected at approximately €1.04 billion, supporting treatment of an estimated 211,380 additional patients. At a 70% discount, savings increased to €1.44 billion, with the potential to treat up to 479,457 additional patients. Variations in market share uptake and overall market growth had comparatively modest effects on total savings, which ranged from €576 million to €703 million when uptake assumptions were varied by plus or minus 10%.

The authors acknowledged several limitations. The model did not use a prevalence-based approach because of inconsistent country-level epidemiologic data and limited information on treated populations by indication. Uptake projections relied on adalimumab biosimilar experience, which may not fully reflect prescribing behavior in allergic diseases. The analysis also excluded potential switching from other biologics and did not account for downstream cost offsets, such as reductions in hospitalizations or corticosteroid exposure. Administration costs were omitted under the assumption of therapeutic equivalence and similar delivery methods.

Despite these constraints, the analysis suggested that biosimilar entry could meaningfully alter the cost profile of omalizumab in Europe. By lowering acquisition costs, biosimilars may improve cost-effectiveness ratios and influence reimbursement decisions in settings where access has been limited. For payers managing constrained pharmaceutical budgets, the projected savings highlight the role biosimilars may play in expanding access to biologic therapy while moderating expenditure growth.

Jang M, Lee J, Kwon TS. Budget impact of introducing an omalizumab biosimilar in 23 European countries. 

2025;28(1);1639-1650. doi:10.1080/13696998.2025.2558450

Canonica GW, Colombo GL, Rogliani P, et al. Omalizumab for severe allergic asthma treatment in Italy: a cost-effectiveness analysis from PROXIMA study. 

. 2020;13:43-53. doi:10.2147/RMHP.S211321

Budget impact analysis finds omalizumab biosimilars in Europe could cut payer costs by €641M in 5 years, expanding access and driving major omalizumab savings.

Omalizumab Biosimilar Entry Linked to Expanded Patient Access, Reduced Spending

Since the first launch in 2015, biosimilars have fundamentally reshaped the US health care system, generating over $56 billion in savings, according to the 

Biosimilars save billions, yet FDA streamlining, payer hurdles and Humira switchbacks expose a looming void in US biologic competition. | Image credit: alexkich - stock.adobe.com

Although biosimilars have generated billions in cumulative health care savings over the previous decade, new data suggest that achieving long-term market sustainability remained a complex objective. By early 2026, biosimilars accounted for approximately 23% of the total biologics market in the US. While the market demonstrated significant growth, stakeholders identified a "biosimilar void" that could result in $232 billion in missed savings over the next 10 years if current development and adoption trends do not accelerate.

The regulatory environment for biosimilars underwent a significant shift in late 2025. The FDA issued draft guidance that proposed the elimination of comparative efficacy studies (CES) for most biosimilar applications.

 This change was intended to streamline the approval process by focusing on analytical data rather than costly clinical trials. The FDA estimated that this shift could save manufacturers up to $100 million in development costs per product and reduce development timelines by as much as 50%.

Looking forward, the pipeline for these therapies remains active. Nearly 25 new biosimilars are expected to receive FDA approval between 2026 and 2027, targeting therapeutic areas such as oncology, immunology, and retina. Despite this activity, a substantial gap persists; while more than 110 biologics are set to lose patent protection over the next decade, only 10% of those products have biosimilars currently in development.

Physician Perspectives and Adoption Drivers

A Cardinal Health survey of 101 physician practices in late 2025 revealed high levels of clinical confidence alongside persistent operational concerns. Approximately 99% of participating providers reported they felt confident explaining biosimilars to their patients. The survey indicated that adoption was primarily driven by clinical data (56%) and payer requirements (50%).

However, physicians also identified significant points of hesitancy. The leading concern, cited by 53% of respondents, involved the nonmedical switching of a long-term, stable patient from a reference biologic to a biosimilar. Reimbursement complexities were also noted as a barrier by 34% of the surveyed practices. Furthermore, 94% of respondents stated that a stable reimbursement rate for medical benefit biosimilars was an important factor in their utilization decisions.

The Adalimumab Case Study and the "Switchback" Phenomenon

The launch of adalimumab biosimilars provided a critical real-world test for market disruption. Although biosimilar adoption increased significantly, research from Truveta through April 2025 identified a notable "switchback" trend. Data showed that 13.2% of patients who initially transitioned to an adalimumab biosimilar eventually reverted to the reference biologic, Humira.

This phenomenon was particularly prevalent among older adults and patients with rheumatoid arthritis or ankylosing spondylitis. Notably, nearly 40% of these switchbacks occurred within the first 30 days of treatment. Experts attributed this trend largely to the nocebo effect—a psychological phenomenon where a patient's negative perceptions or anxiety regarding a new medication led to perceived worsened clinical outcomes or adverse events.

Specialty Trends: Oncology and Gastroenterology

The impact of biosimilars varied by specialty. Oncology remained the most mature market, achieving an average 81% market share within 5 years of initial competition. In contrast, community gastroenterology practices faced increasing operational complexity. These practices managed the simultaneous launch of 3 different biosimilar classes: infliximab, adalimumab, and ustekinumab.

 For these providers, the primary challenges included navigating frequently changing payer formularies and managing the logistics of a growing inventory of similar but nonidentical products.

The report concluded that the long-term viability of the biosimilar market depended on aligning stakeholder incentives and stabilizing reimbursement models. To address the projected "biosimilar void," the authors suggested that proactive policy measures were necessary to ensure that the health care system could realize the billions of dollars in potential savings offered by these therapies. 

2026 biosimilars report: driving access and patient outcomes in physician practices. Cardinal Health. February 24, 2026. Accessed February 24, 2026. 

https://www.cardinalhealth.com/en/product-solutions/pharmaceutical-products/biosimilars/biosimilars-report.html

Jeremias S. The biosimilar void: 90% of biologics coming off patent will lack biosimilars. The Center for Biosimilars

. February 5, 2025. Accessed February 24, 2026. 

https://www.centerforbiosimilars.com/view/the-biosimilar-void-90-of-biologics-coming-off-patent-will-lack-biosimilars

A closer look at new FDA guidance removing barriers to biosimilar development. The Center for Biosimilars. October 30, 2025. Accessed February 24, 2026. 

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

Jeremias S. Adalimumab double take: the unexpected return to reference Humira. The Center for Biosimilars. June 30, 2025. Accessed February 24, 2026. 

https://www.centerforbiosimilars.com/view/adalimumab-double-take-the-unexpected-return-to-reference-humira

Biosimilars save billions, but FDA’s new guidance, physician concerns, and Humira switchbacks reveal hurdles to a sustainable US market.

Cardinal Health Biosimilar Report: $56 Billion in Savings and the Road to Market Sustainability

Access to antibody-drug conjugates remains uneven in many low- and middle-income countries, leaving clinicians to balance evidence-based care with financial realities.

 In that context, new real-world data from India evaluated whether a trastuzumab emtansine biosimilar could deliver outcomes comparable to the reference product for patients with HER2-positive metastatic breast cancer.

Real-world data from India evaluated whether a trastuzumab emtansine biosimilar could deliver outcomes comparable to the reference product for patients with HER2-positive metastatic breast cancer. | Image credit: Bangkok Click Studio - stock.adobe.com

In a retrospective, single-center analysis 

, Chandrakanth and colleagues assessed the safety and effectiveness of Ujvira (ZRC-3256), a biosimilar to trastuzumab emtansine (T-DM1), in 51 patients treated at a tertiary oncology center in India. The reference product, Kadcyla, had previously demonstrated improved progression-free survival (PFS) and overall survival in phase 3 trials such as EMILIA and TH3RESA. However, high acquisition costs limited its availability in many resource-constrained settings, prompting interest in lower-cost biosimilar alternatives.

All patients in the current cohort had HER2-positive metastatic breast cancer and prior exposure to trastuzumab. Ujvira was administered intravenously at 3.6 mg/kg every 21 days until disease progression or unacceptable toxicity. The primary end point was PFS, estimated using the Kaplan-Meier method. Secondary end points included objective response rate (ORR), safety as graded by CTCAE version 5.0, and exploratory subgroup analyses based on clinical and biomarker characteristics.

The mean (SD) age of participants was 58.0 (8.4) years, and 49.0% were 60 years or older. Most patients were postmenopausal (92.2%) and had an Eastern Cooperative Oncology Group performance status of 1 (64.7%). Comorbidity burden was notable: 60.8% had hypertension, and 58.8% had type 2 diabetes. More than 40% had at least 3 metastatic sites at baseline. HR-positive disease was common, with estrogen receptor positivity in 70.6% and progesterone receptor positivity in 54.9%. Nearly three-quarters (74.5%) had HER2 immunohistochemistry 3+ tumors, and 23.5% were fluorescence in situ hybridization–positive.

Patients were heavily pretreated. All had received prior trastuzumab; 84.3% had prior taxane exposure, 62.7% anthracyclines, 39.2% lapatinib, and 19.6% pertuzumab. Forty patients (78.4%) received Ujvira in the second-line setting, and 11 (21.6%) in the third-line setting.

Median PFS for the overall cohort was 6.9 months (95% CI, 6.2-9.0). In second-line use, median PFS was 7.7 months (95% CI, 6.2-10.5), compared with 9.1 months (95% CI, 1.47-not estimable) in the third-line setting; the difference was not statistically significant (

Exploratory subgroup analyses showed numerical but not statistically significant differences across clinical characteristics. Patients with brain metastases had a median PFS of 6.3 months compared with 9.1 months in those without central nervous system involvement (

 = .2203). Patients with diabetes had a median PFS of 7.0 months vs 9.37 months among those without diabetes (

 = .2405). Progesterone receptor–positive tumors were associated with numerically longer PFS (9.37 vs 7.7 months), although this did not reach statistical significance.

Treatment was generally well tolerated. The most common adverse events of any grade were thrombocytopenia (33.3%), anemia (19.6%), and neutropenia (7.8%). Elevated transaminases occurred in 3.9% of patients and represented the only reported grade 3 or higher toxicity. Reduced left ventricular ejection fraction below 50% was observed in 3.9% of patients. Dose reductions were required in 15.7% of patients because of treatment-related toxicities. Median PFS was similar among those who required dose reductions and those who did not (6.8 vs 6.9 months; 

 = .25), suggesting that dose modification did not appear to compromise effectiveness.

When contextualized against registrational trials of the reference product, the observed median PFS was shorter than the 9.6 months reported in the EMILIA study. The authors attributed this difference to the real-world nature of the cohort, including substantial comorbidity burden and prior exposure to multiple HER2-directed therapies. They also noted alignment with other real-world studies of T-DM1 that reported median PFS of approximately 6 months.

The study had several limitations. Its retrospective, single-center design introduced the potential for selection and reporting bias. The sample size was modest, limiting statistical power for subgroup comparisons and increasing the risk of type II error. Overall survival data were immature at the time of analysis, precluding robust comparisons with global benchmarks. Additionally, 2 authors were affiliated with the biosimilar’s manufacturer, although they reported limited roles in study conceptualization and manuscript review.

Despite these constraints, the findings add to the growing body of real-world biosimilar evidence in oncology. For managed care stakeholders in resource-limited settings, the data suggest that trastuzumab emtansine biosimilars may provide clinically meaningful disease control with a safety profile consistent with prior experience, even among heavily pretreated and comorbid patient populations.

Montemurro F, Delaloge S, Barrios CH, et al. Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial. 

. 2020;31(10):1350-1358. doi:10.1016/j.annonc.2020.06.020

Chandrakanth MV, Agarwala V, Manna R, et al. Real-world evaluation of a trastuzumab emtansine biosimilar (Ujvira) in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. 

. Published online February 16, 2026. doi:10.7759/cureus.103700


Real-world India data show trastuzumab emtansine biosimilars deliver meaningful PFS and manageable safety in heavily pretreated HER2+ metastatic breast cancer.

Biosimilar Trastuzumab Emtansine Shows Consistent PFS in HER2-Positive Breast Cancer

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

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.