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

Skylar Jeremias

The US biosimilar market recently saw the introduction of 2 pairs of denosumab biosimilars from Fresenius Kabi and Celltrion USA, significantly expanding treatment options for individuals living with bone-related conditions.

The pairs of denosumab competitors follow the launches of Sandoz’ Wyost and Jubbonti (denosumab-bbdz for both), which launched in March 2025. | Image credit: SoftSheep - stock.adobe.com


 the commercial availability of Conexxence (denosumab-bnht) and Bomyntra (denosumab-bnht). Conexxence is a biosimilar referencing Prolia (denosumab), and Bomyntra is a biosimilar referencing Xgeva (denosumab). The biosimilars 

 from the FDA for all indications of their respective reference products in March 2024.

Conexxence is indicated for various adult patient populations at high risk for fractures.

 This includes individuals with osteoporosis, people undergoing certain cancer treatments that affect bone density, and patients receiving long-term glucocorticoid therapy. It is available in a 60-mg/mL single-use prefilled syringe. Fresenius Kabi noted that Conexxence carries a black box warning and is part of a Risk Evaluation and Mitigation Strategy program designed to inform prescribers and patients about the risk of severe hypocalcemia in individuals with advanced chronic kidney disease, including those on dialysis. The biosimilar is contraindicated in patients with hypocalcemia, during pregnancy, and in cases of known hypersensitivity to denosumab products.

Bomyntra is approved for the prevention of skeletal-related events in patients with multiple myeloma and in individuals with bone metastases from solid tumors. It is also indicated for the treatment of hypercalcemia of malignancy that is refractory to bisphosphonate therapy and for the treatment of adults and skeletally mature adolescents with giant cell tumor of the bone that is unresectable or where surgical resection is likely to result in severe morbidity. Bomyntra is available in a 120-mg/1.7-mL vial and a 120-mg/1.7-mL single-use prefilled syringe. It is contraindicated in patients with hypocalcemia and those with known hypersensitivity to denosumab products.

Sang Jin Pak, PhD, president of Fresenius Kabi Biopharma, expressed the company’s commitment to consistent biosimilar launches, stating, “Access to high-quality biological medicines creates the opportunity to provide more affordable therapies to patients and as our biosimilar portfolio expands, we will be able to provide access for even more patients.” Earlier this year, Fresenius Kabi reached a global settlement with Amgen regarding its denosumab biosimilars.

 the commercial availability of its denosumab biosimilars, Stoboclo (denosumab-bmwo) and Osenvelt (denosumab-bmwo). Stoboclo references Prolia (denosumab), while Osenvelt references Xgeva (denosumab).

Stoboclo is available as a 60-mg/mL injection. It is approved to treat postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with osteoporosis at high risk for fracture, and to treat glucocorticoid-induced osteoporosis in men and women at high risk for fracture. Additionally, it is indicated to increase bone mass in men at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer and to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

Osenvelt, available as a 120-mg/1.7-mL (70 mg/mL) injection, is indicated to prevent skeletal-related events in patients with multiple myeloma and in individuals with bone metastases from solid tumors. It is also approved to treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity and to treat hypercalcemia of malignancy refractory to bisphosphonate therapy.

Thomas Nusbickel, chief commercial officer at Celltrion USA, highlighted the significance of the launches, stating, "We are proud to introduce our denosumab biosimilars to the U.S. market, offering patients and professionals a valuable alternative treatment option." Celltrion also reached a global settlement with Amgen concerning its denosumab biosimilars. To support patients, Celltrion offers comprehensive patient support programs, including the Celltrion Connect patient support program and the Celltrion Cares co-pay assistance program, with options for uninsured patients to potentially receive treatment at no cost.

The pairs of denosumab competitors follow the launches of Sandoz’ Wyost and Jubbonti (denosumab-bbdz for both), which launched in March 2025, nearly a year after they became the first denosumab biosimilars to be greenlit by the FDA.

Now that Xgeva and Prolia have 3 competitors each, the market is starting to stack up, with 

 (denosumab-dssb for both), which were developed by Samsung Bioepis are waiting in the wings to launch next.

“By providing quality-proven biosimilars, we are helping to address a critical healthcare need and reduce the burden of skeletal fractures that impact patients’ quality of life,” Byoungin Jung, vice president and regulatory affairs team leader at Samsung Bioepis, commented.

1. Fresenius expands biosimilars portfolio with the launch of denosumab biosimilars in the U.S. News release. Fresenius Kabi. July 1, 2025. Accessed July 9, 2025. 

https://www.businesswire.com/news/home/20250701511446/en/Fresenius-Expands-Biosimilars-Portfolio-With-The-Launch-of-Denosumab-Biosimilars-in-the-U.S

2. Celltrion USA announces U.S. launch of denosumab biosimilars, Stoboclo and Osenvelt (denosumab-bmwo). News release. Celltrion USA. July 7, 2025. Accessed July 9, 2025. 

https://www.prnewswire.com/news-releases/celltrion-usa-announces-us-launch-of-denosumab-biosimilars-stoboclo-and-osenvelt-denosumab-bmwo-302499495.html

3. Santoro C. FDA approves another pair of denosumab biosimilars, Conexxence and Bomyntra. The Center for Biosimilars

. March 27, 2025. Accessed July 9, 2025. 

https://www.centerforbiosimilars.com/view/fda-approves-another-pair-of-denosumab-biosimilars-conexxence-and-bomyntra

4. Jeremias S. FDA approves third pair of denosumab biosimilars. The Center for Biosimilars. March 4, 2025. Accessed July 9, 2025. 

https://www.centerforbiosimilars.com/view/fda-approves-third-pair-of-denosumab-biosimilars

5. Jeremias S. Wyost and Jubbonti launch as first denosumab biosimilars in the US. The Center for Biosimilars. June 2, 2025. Accessed July 9, 2025. 

https://www.centerforbiosimilars.com/view/wyost-and-jubbonti-launch-as-first-denosumab-biosimilars-in-the-us

6. Jeremias S. FDA, EMA approve second pair of denosumab biosimilars. The Center for Biosimilars. February 17, 2025. Accessed July 9, 2025. 

https://www.centerforbiosimilars.com/view/fda-ema-approve-second-pair-of-denosumab-biosimilars

Articles

The US biosimilar market expands with new denosumab options, enhancing treatment for patients with osteoporosis and bone-related metastases.

Two More Pairs of Denosumab Biosimilars Enter US Market

Despite the growing presence of biosimilar insulins in the market, a new narrative review underscored persistent concerns among health care providers and patients regarding their efficacy, safety, and quality compared with reference products.

Image credit: 86008201-644px - stock.adobe.com

, dissected the rigorous regulatory pathways in the European Union (EU) and the US, ultimately confirming the safety of insulin biosimilars and confirming that people with diabetes and prescribers should be able to use approved biosimilars without concerns.

Authors of the review highlighted that although 6 biosimilar insulins were approved in the EU and 4 in the US, their commercial success had been limited, largely attributed to lingering skepticism.

 To address these concerns and provide a definitive answer on the comparability of biosimilar insulins, the narrative review examined the regulatory framework and pivotal studies supporting the registration of these products in the EU and US.

The study emphasized the multifaceted approach taken by regulatory bodies. It detailed the necessity of:

Comparative analytical and functional studies:

 These confirmed the primary, secondary, and higher-order structures of the biosimilar, along with post-translational modifications, ensuring molecular similarity.

 These investigated receptor binding and activation in cell models, assessing how biosimilar insulins induced their effects. For insulin, this included affinity to insulin receptors and studies on metabolic activity in cell cultures.

Pivotal clinical pharmacology studies using the euglycemic glucose clamp technique:

 This was the cornerstone of biosimilar insulin approval. In a double-blind, crossover design, a single subcutaneous dose of the biosimilar and reference insulin was administered, and blood glucose levels were meticulously "clamped" at a predefined level using a variable glucose infusion. The glucose infusion rate profile directly reflected the insulin's pharmacodynamic effect, while frequent blood samples established the pharmacokinetic profile. This highly sensitive method was preferred, as it could detect subtle differences that larger clinical efficacy studies might miss.

 Although not always strictly required for approval due to the sensitivity of clamp studies, these trials provided additional data on clinical safety, efficacy (eg, HbA1c), and immunogenicity.

The authors noted that both the European Medicines Agency (EMA) and FDA shared identical acceptance criteria for pharmacokinetic endpoints, with EMA having stricter criteria for pharmacodynamic endpoints. It also pointed out that whereas initial approvals involved multiple clamp studies, more recent approvals had relied on a single pivotal automated clamp study, consistently confirming biosimilarity.

The review was prompted by the low adoption of biosimilar insulins, despite their potential to reduce costs.

 Ongoing hesitation from prescribers and patients revealed a clear gap in understanding around the rigorous approval process for these biologics.

 By explaining the scientific standards behind biosimilar regulation, the review aimed to dispel misconceptions and build trust.

According to the researchers, their findings carry important implications for the biosimilar market and the US health care system. By confirming that biosimilar insulins are just as safe and effective as their reference products, the review supports increased uptake, which could help expand market share. Broader use may also lead to price competition, resulting in lower insulin costs and improved access for patients.

The review reinforced how evolving FDA guidance on interchangeability could make pharmacy-level substitution more feasible, improving convenience and access for patients.

“A clear regulatory framework ensures the efficacy and safety of biosimilar insulins in Europe and the US (and many other countries not considered in this review). This regulatory framework is based on scientific evidence that the demonstration of similar physico‐chemical properties and biological activity in preclinical studies and of pharmacological bioequivalence in glucose clamp studies is sufficient to make sure that the minor differences in the formulations between biosimilar and reference insulins are not of clinical relevance,” the authors concluded.

1. Heise T, DeVries JH. Biosimilar insulins: Narrative review of the regulatory framework and registration studies. 

2. Heinemann L, Davies M, Home P, Forst T, Vilsboll T, Schnell O. Understanding biosimilar insulins – development, manufacturing, and clinical trials. 

3. White J, Wagner A, Patel H. The impact of biosimilar insulins on the diabetes landscape. 

A recent review confirms the safety and efficacy of biosimilar insulins, addressing concerns and promoting their adoption for diabetes treatment.

Dispelling Doubts: Review Affirms Safety, Efficacy of Biosimilar Insulins

Despite the growing presence of biosimilar prescription drugs in the US health care market, a recent analysis revealed significant knowledge gaps and uncertainties among both consumers and health care professionals (HCPs).

 This widespread lack of understanding could hinder the full potential of biosimilars, which are poised to expand access to life-saving medications and potentially lower health care costs across the nation. The findings underscored an urgent need for clearer, more comprehensive educational initiatives to foster better understanding and adoption of these crucial therapeutic options.

The authors said their findings underscore an urgent need for clearer, more comprehensive educational initiatives to foster better understanding and adoption of these crucial therapeutic options. | Image credit: Alena - stock.adobe.com

The abbreviated approval pathway for biosimilars is rigorous, allowing for more affordable treatment options and increased patient access to crucial medications for conditions like chronic skin diseases, arthritis, and cancer. However, prior research had consistently shown a lack of familiarity and understanding of biosimilars among both patients and prescribers. Misconceptions around their efficacy, safety, and interchangeability had created hesitancy in their adoption.

With the FDA having issued draft guidance in 2020 on promotional labeling and advertising for biosimilars, particularly concerning disclosure statements, the present study aimed to experimentally test how different forms of disclosure impacted understanding and perceptions.

 The goal was to identify effective communication strategies that could inform and educate both groups in a neutral manner, dispelling misconceptions without unduly influencing perceptions.

The study employed an experimental design involving 379 consumers and 368 HCPs (primary care providers with prescribing authority) recruited via an online panel. Participants were randomized into one of seven biosimilar disclosure conditions or a control group.

Each condition presented a mock advertisement for "Kesterin," a fictitious biosimilar for rheumatoid arthritis. Disclosures varied by: identifying the product as a biosimilar; the comprehensiveness of the definition provided (ranging from basic to expanded details on safety, efficacy, source, dosage, and administration); and whether a specific reference product ("Mytrozen") was named. Consumer disclosures used lay language, while HCP disclosures used medical terminology. Researchers assessed the impact of these disclosures on participants' comprehension, perceptions of benefit and risk, attitudes, intentions (to use or prescribe), and preferences.

The study's results highlighted significant knowledge gaps. Overall, comprehension of biosimilar information was suboptimal, even when participants were provided with a definition. Only 48.5% to 62.0% of consumers and 68.4% to 88.4% of HCPs accurately understood core characteristics, such as comparable safety and efficacy.

Specifically, comprehension was lowest for the statement, "Kesterin has the same safety and efficacy as the original biologic," for both groups. Perceptions of benefit, comparative efficacy, and safety remained largely neutral across all groups, including the control, suggesting that existing perceptions were deeply ingrained and not easily shifted by brief disclosures.

Crucially, the content of the biosimilar definition generally did not significantly influence outcomes for consumers. However, for HCPs, expanded definitions led to more positive attitudes toward the biosimilar drug and stronger intentions to prescribe. For instance, HCPs exposed to the most comprehensive definition reported more positive attitudes (mean, 4.23) compared to those who only saw the "Kesterin is a biosimilar" statement (mean, 3.83; 

 = .014) or the control group (mean, 3.80; 

 = .009). Similarly, their intentions to prescribe were significantly higher with expanded definitions (mean = 3.76) compared to the control (mean, 3.21; 

 = .009) or the biosimilar-only condition (mean, 3.00; 

Both consumers and HCPs expressed a preference for these more detailed definitions. HCPs also specifically preferred seeing the named reference product, although this did not directly impact other study outcomes, possibly due to the fictitious nature of the named reference product. Notably, HCPs largely agreed that biosimilars could be used "interchangeably" with their reference product, which signaled a potential misunderstanding of the specific regulatory designation of "interchangeability."

These findings had significant implications for the biosimilar industry and the US health care system. The persistent knowledge gaps and neutral perceptions among both consumers and HCPs indicated that the full potential of biosimilars, including their cost-saving benefits and increased access to treatment, might not be fully realized.

"Our findings clearly signaled that there were knowledge gaps and uncertainty regarding biosimilar products among consumers and HCPs," the study authors concluded. "Further education was warranted around these products, and communications for both groups required careful testing to ensure that the information was understood and did not result in a negative perception of the product."

Researchers suggested that future educational efforts should focus on providing comprehensive and easily digestible information, particularly for HCPs, given their stated preference for expanded definitions and their increased prescribing intentions when presented with more detail. For the biosimilar industry, this means refining direct-to-consumer and professional-facing promotional materials to incorporate clearer, more informative disclosures that addressed core misconceptions about biosimilar equivalence, safety, and efficacy.

For the broader health care system, effective education was mentioned by the authors as paramount to fostering trust and increasing the adoption of these important therapeutic options, which will ultimately contribute to better patient outcomes and more sustainable health care spending.

1. Johnson M, Thompson JE, Tilley AA, O’Donoghue AC, Aikin KJ. Perceptions and preferences for defining biosimilar products in prescription drug promotion. 

2. FDA. Promotional labeling and advertising considerations for prescription biological reference and biosimilar products questions and answers: Guidance for industry. 2020. Accessed July 1, 2025. 

https://www.fda.gov/media/134862/download

Significant knowledge gaps about biosimilars persist among consumers and healthcare professionals, hindering their adoption and potential benefits in health care.

Consumers and Providers Face Biosimilar Knowledge Hurdles

 of nonmedical switching from the infliximab reference product to biosimilar CT‐P13 (Inflectra; Celltrion) found long-term persistence was similar between patients in the switched and non-switched cohorts after 4 years of follow-up. The investigators said the results “provide further reassurance that nonmedical switching is safe and clinically comparable to ongoing originator infliximab in clinically stable patients with IBD.”

Image credit: Sandor Kacso - stock.adobe.com

 shown nonmedical switching to the infliximab biosimilar CT‐P13 from the originator was safe and noninferior compared to continuing the reference product in patients with inflammatory bowel disease (IBD).

Although several studies have reported cost savings associated with switching to infliximab, and several countries and regions require new prescriptions of anti-tumor necrosis factor biologics to be biosimilars, Australia does not mandate prescribing biosimilars, “and a significant portion of [IBD] patients may remain on originator infliximab owing to clinician and patient reluctance to switch.”

Randomized controlled trials and real-world studies have found infliximab biosimilars are safe and effective in IBD, for both infliximab-naive and switched patients. However, longer-term outcomes “remain less well described,” the authors said. Furthermore, they added, since some studies have suggested switching may negatively affect long-term clinical outcomes due to the nocebo effect, there is a need for longer-term studies.

The prospective parallel cohort noninferiority study enrolled 345 patients with IBD in steroid-free clinical remission across multiple centers in Australia on the originator infliximab. Patients either continued treatment with the originator (n = 141) or switched to CT‐P13(n = 204). Independent of the study, 4 hospitals had decided to switch all stable patients to the biosimilar, while 3 had decided to continue to use the originator.

At 48 weeks, treatment persistence, the primary outcome, was 92% among patients in the biosimilar group, and 94% in the originator group. Among patients who did not change from their initial treatment (n = 297) during follow-up, there was no difference in the risk of disease worsening between groups (HR, 1.08; 95% CI, 0.68-1.72).

Trough drug levels were not different between switch and non-switch over time or at any single time period throughout the follow-up. However, the authors did find that patients who were receiving dose escalation prior to the start of the study had lower drug levels than those who weren’t. Also, dose escalation of more than 5 mg/kg every 8 weeks was significantly associated with disease worsening (HR, 1.89; 95% CI, 1.13-3.17).

Rates of antidrug antibodies (ADAs) were similar between groups. Develoment of ADAs occurred in 5 patients in the switch group and 4 who remained on the originator. Overall rates of ADAs were similar between groups, at 10% in the switch group and 11% in the reference product group. The authors added that all patients who developed “clinically significant” antibodies had a change in drug therapy sometime during follow-up.

At least 1 adverse event (AE) occurred in 49% of patients in the biosimilar group and 53% of the reference product group, with no significant difference between groups. The authors said most AEs were mild and did not affect treatment persistence. In the biosimilar group, 25 patients (12%) experienced an AE leading to discontinuation of infliximab treatment, as well as 15 (11%) of patients in the reference product group. AEs leading to discontinuation included infection, vasculitis, drug‐induced lupus, and one death, which was associated with a pre‐existing malignancy.

Rates of infliximab discontinuation were also not significantly different between groups, occurring 35% in the switched group and 38% of those who stayed on the reference product (HR, 0.87; 95% CI, 0.59-1.28). One patient switched back to the originator, after a change in symptoms without objective evidence of inflammation.

Reasons for discontinuation included disease worsening (22% of those who discontinued the biosimilar and 24% of those who discontinued the reference product), dose escalation (35% and 32%), antibody development (5% and 11%), and infliximab‐related adverse events (8% and 8%), and were comparable between groups. Regardless of group, patients with UC had a higher likelihood of treatment discontinuation than those with CD.

According to the authors, this is the longest real-world study to compare switched and non-switched groups of patients with IBD on infliximab. The authors concluded their findings “provide reassurance to clinicians, patients, and healthcare payers, alike, regarding the long‐term safety, clinical effectiveness, and pharmacokinetic profile of nonmedical switching.”

Suo P, Srinivasan A, Thin L, et al. Comparing long-term infliximab persistence following a switch to a biosimilar in patients with inflammatory bowel disease: no cause for concern. 

. 2025;40(5):1174-1181. doi:10.1111/jgh.16916

Long-term data from the SAME study confirm that switching to infliximab biosimilars is safe and effective for patients with inflammatory bowel disease (IBD).

Australian Patients With IBD Switched to Biosimilar Infliximab Maintain Long-Term Persistence

 assessed the safety of the infliximab biosimilar CT-P13 (Inflectra) after switching from the reference product (Remicade) in Japanese patients with Crohn disease (CD), ulcerative colitis (UC), and rheumatoid arthritis (RA). Among patients with CD, 39% experienced at least one uncommon adverse drug reaction (ADR), as well as 50% of patients with UC and 13% with RA. However, most ADRs (94%) were considered not related to CT-P13.

The tumor necrosis factor (TNF)-α inhibitor infliximab is used to treat a variety of immune-mediated inflammatory diseases, including IBD (CD and UC) and RA, in which the cytokine TNF plays a central role. 

 was the first infliximab biosimilar and first biosimilar monoclonal antibody approved in Japan in 2014. Clinical trials and real-world studies have established CT-P13 is similarly effective and safe as the originator, however, according to the authors, there are few studies on long-term CT-P13 treatment in Japan, where patient co-pays for biosimilars and originators are the same.

Data on 220 patients was collected in routine clinical practice at multiple centers in Japan, 123 of whom had CD, 74 with UC, and 23 with RA. Patients were stable on the reference product prior to switching to CT-P13. The study is ongoing with patients continuing to complete annual follow-up visits.

After 2 years of CT-P13 therapy, 48 (39%), 37 (50%), and 3 (13%) patients with CD, UC, and RA reported at least 1 ADR. However, the vast majority (94%) were not related to CT-P13. Most ADRs (74%) were grade 1 or 2. The most frequent classes of ADRs reported were gastrointestinal disorders in 11% of patients with CD, infections and infestations in 20% of patients with UC, and injury, poisoning, and procedural implications in 9% of patients with RA.

Adverse events (AEs) and serious AEs (SAEs) were secondary endpoints of the study. AEs were reported by 59% of patients with CD, 70% of patients with UC, and 30% of patients with RA. Serious AEs were reported by 10%, 13.5%, and 9% of patients. Most AEs were grade 1 or 2 and most SAEs were grade 2 or 3. The most frequent AEs were gastrointestinal disorders in patients with CD (40%) and UC (40.5%), and infections and infestations in patients with RA (17%). Herpes zoster infection and pneumonia in patients with CD and UC and nasopharyngitis in patients with RA were considered to have a “plausible relationship to CT-P13 treatment.” One patient with CD and 4 patients with UC reported infusion-related reactions.

Nineteen patients (9%) discontinued CT-P13 for reasons related to the drug, 4 (9%) with CD, 11 (31%) with UC, and 4 (31%) with RA. The primary reason was loss of efficacy in patients with UC and RA, and AEs in patients with CD. Two patients with CD and 1 with UC experienced SAEs leading to discontinuation of treatment.

The authors concluded that CT-P13 was “well tolerated” over 2 years in this study, as most ADRs were not related to CT-P13, and few patients stopped treatment due to reasons related to the biosimilar. They added that the effectiveness of infliximab therapy was “well maintained,” and said their findings demonstrate long-term safety of CT-P13 in real-world practice. They plan to report 5-year data at the completion of the study.

Ishida T, Yokoe I, Obata H, Park S, Kim S, Nishimata N. A real-world, observational, prospective cohort study evaluating the safety and effectiveness of CT-P13 in inflammatory bowel disease and rheumatoid arthritis: the MEGA-J study. 

. 2025;41(4):601-606. doi:10.1080/03007995.2025.2492638

The MEGA-J study reveals CT-P13's long-term safety and effectiveness in treating inflammatory bowel disease and rheumatoid arthritis, with minimal adverse reactions.

Real-World Data Suggest Long-Term Safety of CT-P13 in IBD, RA

Recent developments in rheumatology highlight progress in biosimilar access and use, including FDA approval of a pediatric indication for Steqeyma, setbacks and partnerships affecting adalimumab biosimilars in global markets, real-world insights into patient switching patterns, and new clinical data supporting the safety, efficacy, and usability of biosimilars like CT-P47 for rheumatoid arthritis.

Celltrion announced that the FDA approved a new 45 mg/0.5 mL single-dose vial formulation of Steqeyma (ustekinumab-stba), a biosimilar to Stelara (ustekinumab), expanding dosing options for pediatric patients aged 6 to 17 years with plaque psoriasis or psoriatic arthritis who weigh less than 60 kg.

The approval enhances dosing precision for a vulnerable population with variable weight-based needs, complementing previously approved formulations for both adult and pediatric use. With full interchangeability status across all Stelara indications, Steqeyma’s expanded offerings support improved access, treatment flexibility, and cost-effective care.

In recent business news, Samsung Bioepis faced a significant legal setback in Germany as the Düsseldorf Higher Regional Court ruled that its adalimumab biosimilar, Imraldi, infringed on a formulation patent held by Fresenius Kabi.

 The decision bans Imraldi sales in Germany, mandates a product recall, and imposes financial penalties, threatening broader disruptions across the European Union, where the patent remains valid. 

Meanwhile, Samsung Bioepis announced a new strategic partnership with NIPRO Corporation in Japan to codevelop and commercialize biosimilars, including an ustekinumab candidate (SB17).

Real-World and Switching Data on Adalimumab Biosimilars

A recent Truveta analysis found that 13.2% of patients who switched from Humira to an adalimumab biosimilar ultimately returned to the originator, with nearly 40% of these switchbacks occurring within 30 days.

 While this trend may raise concerns about biosimilar efficacy, experts caution that factors like patient perception, limited biosimilar awareness, and the nocebo effect—rather than product failure—are likely driving these reversals. Older adults, women, and rural patients were more prone to switch back, highlighting the need for targeted education and support. The report also underscores the importance of ongoing evaluation of US interchangeability policies, especially as biosimilar adoption grows in response to formulary changes by major pharmacy benefit managers.

In other adalimumab data news, a study published in 

 provided the pivotal evidence behind the FDA’s decision to grant Hulio (adalimumab-fkjp) interchangeable status with Humira (reference adalimumab).

 In a randomized trial of patients with moderate to severe plaque psoriasis, those who underwent multiple switches between Hulio and the reference biologic showed no differences in pharmacokinetics, safety, efficacy, or immunogenicity compared to those who remained on Humira. These findings fulfill FDA requirements for interchangeability and support pharmacist-level substitution without prescriber approval, which can boost biosimilar uptake, reduce costs, and expand access. Hulio’s designation marks a key milestone in advancing biosimilar integration into US health care.

Real-world data from a large cross-sectional survey across five European countries highlights the strong performance of the adalimumab biosimilar ABP 501 (Amgevita/Amjevita) in treating immune-mediated inflammatory diseases (IMIDs).

 The study, which included 1,296 patients either initiating therapy or switching from Humira, found high satisfaction rates among both physicians and patients, with over 89% of physicians and 86% of patients reporting positive experiences. Patients showed improved disease control, reduced pain, and minimal impact on daily life. Even among those who switched for nonclinical reasons—such as cost or formulary changes—treatment effectiveness and quality of life remained consistent. The authors said their findings support the broader adoption of biosimilars like ABP 501 as a cost-effective and clinically sound option in managed care.

In other news on tumor necrosis factor agents, a pilot study published in the 

 found that nearly half of patients with rheumatic diseases who were nonmedically switched from reference infliximab to biosimilars (infliximab-abda or infliximab-dyyb) experienced flares or loss of disease control, with most events occurring within 4 months of the switch.

 Delays in treatment—often due to insurance-mandated switching and prior authorization hurdles—may have contributed to these outcomes. While the small sample size and limited biosimilar availability constrain broader conclusions, the findings underscore the importance of pharmacist involvement in monitoring and educating patients during biosimilar transitions.

Patients with moderate to severe rheumatoid arthritis were able to safely and effectively self-administer the tocilizumab biosimilar CT-P47 using an autoinjector, highlighting the growing role of biosimilars in expanding access and reducing treatment costs. After 12 weeks, participants showed significant improvements in disease activity and reported high satisfaction and ease of use, with no autoinjector malfunctions and mostly mild to moderate adverse events. These results align with prior data on intravenous CT-P47 and reinforce the potential of subcutaneous biosimilar options to support patient independence and alleviate the economic burden of chronic inflammatory diseases.

1. Jeremias S. FDA approves Steqeyma for children with plaque psoriasis, psoriatic arthritis. The Center for Biosimilars

https://www.centerforbiosimilars.com/view/fda-approves-steqeyma-for-children-with-plaque-psoriasis-psoriatic-arthritis

2. Jeremias S. Eye on pharma: Keytruda biosimilar deal; German court bans Imraldi; new biosimilars for Japan. The Center for Biosimilars. June 17, 2025. Accessed July 1, 2025. 

https://www.centerforbiosimilars.com/view/eye-on-pharma-keytruda-biosimilar-deal-german-court-bans-imraldi-new-biosimilars-for-japan

3. Jeremias S. adalimumab double take: the unexpected return to reference Humira. The Center for Biosimilars. June 30, 2025. Accessed July 1, 2025. 

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

4. Jeremias S. New data support Hulio as an interchangeable adalimumab option. The Center for Biosimilars. June 16, 2025. Accessed July 1, 2025. 

https://www.centerforbiosimilars.com/view/new-data-supports-hulio-as-an-interchangeable-adalimumab-option

5. Santoro C. Infliximab biosimilar switch due to flare risk: monitoring patients is crucial for pharmacists. The Center for Biosimilars. June 5, 2025. Accessed July 1, 2025. 

https://www.centerforbiosimilars.com/view/infliximab-biosimilar-switch-due-to-flare-risk-monitoring-patients-is-crucial-for-pharmacists

6. Jeremias S. European data confirm real-world benefits of adalimumab biosimilars. The Center for Biosimilars. June 11, 2025. Accessed July 1, 2025. 

https://www.centerforbiosimilars.com/view/european-data-confirms-real-world-benefits-of-adalimumab-biosimilars

7. Santoro C. Tocilizumab biosimilar CT-P47 shows promise for rheumatoid arthritis self-administration. The Center for Biosimilars. June 19, 2025. Accessed July 1, 2025. 

https://www.centerforbiosimilars.com/view/tocilizumab-biosimilar-ct-p47-shows-promise-for-rheumatoid-arthritis-self-administration

Explore the latest advancements in rheumatology biosimilars, including FDA approvals, patient switching trends, and real-world efficacy insights.

Biosimilars Rheumatology Roundup: June 2025

The launch of adalimumab biosimilars in the United States in 2023 marked a pivotal moment for health care cost savings and patient access, promising to disrupt the long-standing dominance of the originator biologic, Humira.

However, a recent analysis from Truveta, spanning data through April 2025 unveils a concerning trend: more than 13% of patients who initially switched to an adalimumab biosimilar ultimately reverted to the reference drug.

While the Truveta findings hint at patient dissatisfaction or adverse events, they leave crucial questions unanswered: Are the biosimilars themselves to blame? | Image Credit: Maksym - stock.adobe.com

While the Truveta findings hint at patient dissatisfaction or adverse events, they leave a crucial question unanswered: Are the biosimilars themselves to blame? Delving into these critical missing pieces can offer a more comprehensive understanding of the evolving adalimumab biosimilar landscape and the true implications of patient switching patterns.

The research analyzed switching patterns from bio-originator Humira to its biosimilars, finding a significant increase in biosimilar adoption, particularly peaking in April 2024 due to a major formulary change by CVS Health.

 Although biosimilar switching rates remained elevated compared to 2023, the study revealed that a notable proportion of patients—13.2% of those who initially switched—subsequently returned to reference drug Humira.

This "switching back" phenomenon was more prevalent among specific patient demographics: older adults (aged ≥ 65 years), women, and individuals with rheumatoid arthritis or ankylosing spondylitis. A key finding was the rapid nature of these switchbacks, with nearly 40% occurring within 30 days of initiating a biosimilar. Truveta researchers suggested potential early dissatisfaction, adverse events, or patient resistance and uncertainty regarding the new medication. Rural patients also showed higher rates of early switchbacks compared with urban patients.

The study highlighted that although biosimilar uptake is growing, sustained use faces challenges. Patient perceptions, clinical uncertainty, and factors like pharmacy stock or complex health conditions in older adults may contribute to patients reverting to the originator. Understanding these real-world experiences is crucial for promoting broader and more sustained biosimilar adoption, despite clinical trials showing no meaningful differences in safety or efficacy between biosimilars and the originator.

At first glance, the analysis provides a stark insight into the switching patterns of patients receiving adalimumab treatments but there is a significant lack of investigation into the possible reasons behind patients switching back. Although there are mentions of patient perceptions and adverse events after switching to a biosimilar, there is missing context for whether the biosimilars themselves are to blame for patients’ choosing to switch back to Humira. Without this context, it could be implied that biosimilars fail for more than 10% of patients who switch to them, calling into question the safety and efficacy of switching to biosimilars generally.

Overall, a major factor that can cause a patient to switch back from a biosimilar to the reference agent is the nocebo effect, a phenomenon where a patients’ negative opinions about a drug lead to perceived worsened clinical outcomes or adverse events.

Many studies, several of which concern switching between Humira and an adalimumab biosimilar,

 have looked at reference product to biosimilar switching and have found the nocebo effect to be the main cause for patients who switched back, suggesting that switching between biologic products of the same molecule is safe despite some patients still choosing to go back to Humira. Additionally, these studies are often conducted with patients undergoing multiple switches back and forth between products, which is an FDA data requirement to obtain interchangeability status.

Interchangeability is a regulatory designation that allows for pharmacies to exchange a reference product with an approved biosimilar version without waiting for a provider to approve the change first.

 The policy is intended to give patients easier access to their medications and provide pharmacies with better flexibility to deal with supply chain issues and drug shortages. Of the 10 adalimumab biosimilars currently on the market, 8 have interchangeability designations (Cyltezo, Hadlima, Hyrimoz, Simlandi, Yuflyma, Abrilada, Hulio, and Amjevita).

In addition, all states, as well as Puerto Rico, have individual laws regarding interchangeability, most of which concern requirements for patient and/or provider notification that a switch has occurred.

 Currently, 44 states either do not require patients to be notified or require patients to be notified but do not require them to give their consent for the switch, creating a breeding ground for the nocebo effect to occur in chronic patient populations who are typically unaware of what a biosimilar even is. These patients may also have taken many years and treatment failures to settle on a medication that works for them, and a new brand name or injector device could be jarring and anxiety-inducing.

Private labeling has also become popular in the ustekinumab space, another market in which a large number of biosimilars launched within the same year. | Image credit: New Africa - stock.adobe.com

Although Truveta did not look into how interchangeability played into their results,

 it could be worth investigating as the FDA and other governmental bodies consider whether the US should continue to allow interchangeability policy or to follow in the footsteps of the European Union and UK, where regulatory agencies have declared all biosimilars interchangeable.

Additionally, although Truveta did point out that CVS announced that its pharmacy benefit manager Caremark chose to prioritize adalimumab biosimilars on formulary over Humira as a big reason for growing adalimumab biosimilar adoption,

 it left out the several other PBMs that followed suit, overlooking the full extent of how the industry has been bolstering adalimumab biosimilars for success. Notably, the report omitted information on how PBMs Express Scripts, Optum Rx, Prime Therapeutics, Smith Rx, as well as private label pharmacies such as CarePartners Specialty Pharmacy and the Mark Cuban Cost Plus Drug Company have all chosen at least 1 adalimumab biosimilar to embrace.

 In fact, private labeling has also become popular in the ustekinumab space, another market in which a large number of biosimilars launched within the same year.

Sustaining the Biosimilar Momentum: Addressing Perceptions and Policy

The Truveta analysis, although shedding light on the increasing uptake of adalimumab biosimilars, underscores the intricate challenges of maintaining patient adherence. The seemingly high rate of patients reverting to originator Humira, particularly those experiencing early switchbacks, could, at first glance, cast a shadow on biosimilar efficacy and safety.

 However, a deeper dive into the market dynamics reveals that these switchbacks are often less about inherent biosimilar failure and more about the powerful influence of patient perception and the nuances of policy implementation.

Ultimately, the real-world data on adalimumab switchbacks serves as a vital call to action.

 To truly unlock the full potential of biosimilars in the US health care system, stakeholders must move beyond simply encouraging the initial switch. A concerted effort is needed to educate both patients and providers about the robust science underpinning biosimilar safety and interchangeability, actively mitigating the nocebo effect through transparent communication.

Furthermore, ongoing evaluation of interchangeability policies, potentially aligning with the broader European approach of universal biosimilar interchangeability, could further streamline access and build sustained patient confidence. By addressing these challenges, the US adalimumab biosimilar market might be able to fulfill its promise of delivering high-quality, affordable care to the masses.

1. Jeremias S. US welcomes first adalimumab biosimilar, Amjevita. The Center for Biosimilars

. January 31, 2023. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/us-welcomes-first-adalimumab-biosimilar-amjevita

2. Truveta Research. Biosimilar use is on the rise – but 1 in 8 patients return to Humira. Truveta Research. June 23, 2025. Accessed June 29, 2025. 

https://www.truveta.com/blog/research/research-insights/biosimilar-use-humira/

3. CVS to remove Humira from some reimbursement lists in favor of biosimilar options. The Center for Biosimilars. January 6, 2024. Accessed June 29, 2025 . 

https://www.centerforbiosimilars.com/view/cvs-to-remove-humira-from-some-reimbursement-lists-in-favor-of-biosimilar-options

4. Jeremias S. 13 strategies to avoid the nocebo effect during biosimilar switching. The Center for Biosimilars. December 18, 2024. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/13-strategies-to-avoid-the-nocebo-effect-during-biosimilar-switching

5. Jeremias S. Etanercept biosimilar switch shows stable outcomes and disease control in RA. The Center for Biosimilars. May 13, 2025. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/etanercept-biosimilar-switch-shows-stable-outcomes-and-disease-control-in-ra

6. Ferreri D. Switching from Avastin to bevacizumab-bvzr in CRC, NSCLC can reduce Medicare costs. The Center for Biosimilars. May 10, 2025. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/switching-from-avastin-to-bevacizumab-bvzr-in-crc-nsclc-can-reduce-medicare-costs

7. Ferreri D. High acceptance levels after switching to an adalimumab biosimilar for IBD. The Center for Biosimilars. June 14, 2025. Accessed June 29, 2025. 

https://www.centerforbiosimilars.com/view/high-acceptance-levels-after-switching-to-an-adalimumab-biosimilar-for-ibd

8. Jeremias S. New data support Hulio as an interchangeable adalimumab option. The Center for Biosimilars. June 16, 2025. Accessed June 29, 2025. 

9. Considerations in demonstrating interchangeability with a reference product. FDA. May 2019. Accessed June 29, 2025. 

https://www.fda.gov/media/124907/download

10. Interchangeable biological products. FDA. Accessed June 29, 2025. 

https://www.fda.gov/media/151094/download

11. Jeremias S. Happy Birthday adalimumab biosimilars: reflecting on the first year of US competition. The Center for Biosimilars. January 31, 2024. Accessed June 29, 2025. 

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

12. Biosimilar interchangeability laws by state. Cardinal Health. Updated January 2024. Accessed June 29, 2025. 

https://www.cardinalhealth.com/en/product-solutions/pharmaceutical-products/biosimilars/state-regulations-for-biosimilar.html

13. Mazzoni D, Vener C, Mazzocco K, Monzani D, Pravettoni G. The psychological risks associated with the non-medical switch from biologics to biosimilars. 

14. Biosimilar medicines can be interchanged. EMA. September 19, 2022. Accessed June 29, 2025. 

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

15. Guidance on the licensing of biosimilar products. UK MHRA. Accessed June 29, 2025. 

About 13% of patients who switch from Humira to an adalimumab biosimilar switch back to the originator, according to research from Truveta. However, the presented data may not tell the full story.

Skylar Jeremias

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