Pearl Steinzor

Patients with neovascular age-related macular degeneration (nAMD) who transitioned from off-label bevacizumab to a biosimilar and then to a branded anti-VEGF agent had longer injection intervals around transitions and higher modeled costs than patients who transitioned directly to either a biosimilar or branded drug, according to a retrospective cohort study of the IRIS (Intelligent Research in Sight) Registry published in the 

Bevacizumab-to-biosimilar-to-branded transitions delayed nAMD care and cost up to 36% more than direct switches, a 182,757-eye registry study found. | Image Credit: Orawan - stock.adobe.com

“The present analysis found concerning differences in nAMD medication transitions,” wrote the researchers. “In addition to demographic differences in medication transitions, biosimilar use was associated with delays in care, and economic modeling suggests that multiple transitions may not be cost-effective.”

Anti-VEGF injections have transformed outcomes for nAMD, but their use carries a substantial economic burden. Medicare Part B claims data have estimated annual expenditures of roughly $10,000 per beneficiary for agents such as ranibizumab and aflibercept, contributing to interest in lower-cost alternatives such as bevacizumab.

Researchers analyzed IRIS Registry data from 2015 through 2024 for patients with nAMD who received intravitreal anti-VEGF injections. Eyes with gaps of 6 months or more between injections were excluded.

Among 182,757 eyes meeting the inclusion criteria, 136,451 received bevacizumab only, 2,184 transitioned from bevacizumab to a biosimilar, 43,787 transitioned from bevacizumab to a branded agent, and 335 transitioned from bevacizumab to a biosimilar and subsequently to a branded agent. Overall, 24.56% of eyes underwent at least 1 medication transition.

The researchers considered the bevacizumab-to-biosimilar-to-branded sequence a potential real-world step-therapy cohort, although the registry did not establish whether individual transitions were specifically required by payers.

Transitions Were Associated With Longer Injection Intervals

Compared with the injection interval immediately preceding transition, the interval increased by 9.849 days after switching from bevacizumab to a biosimilar, 6.192 days after the bevacizumab-to-biosimilar-to-branded sequence, and 0.982 days after switching directly from bevacizumab to a branded agent (all 

The researchers also found that newer branded agents, including faricimab and aflibercept 8 mg, were associated with an additional 8.6-day delay around transition compared with aflibercept 2 mg (

 < .001). However, interval extension after transition did not differ significantly between the newer agents and aflibercept 2 mg.

Patients with Medicaid or Medicare coverage were less likely to undergo medication transition than patients with commercial insurance, with log odds of −0.384 and −0.208, respectively (

 < .001). The bevacizumab-only cohort had the lowest proportion of commercially insured patients and the highest proportion of patients with Medicaid.

Multistep Transitions Were the Costliest Pathway

In a Monte Carlo economic simulation using medication costs over a 2-year horizon, the bevacizumab-to-biosimilar-to-branded pathway had an average cost of $26,699 per patient. This was 36.3% higher than the $15,525 cost of a direct bevacizumab-to-biosimilar transition and 11.62% higher than the $21,593 cost of a direct bevacizumab-to-branded transition (both 

Bevacizumab-only treatment had an average modeled cost of $1,043. The higher cost of the multistep pathway persisted in 5- and 10-year projections.

A sensitivity analysis using Medicare average sale prices also found the multistep pathway to be the most expensive. However, the difference between the multistep pathway and direct bevacizumab-to-branded treatment was only 1.6% and was not statistically significant (

 = 1), whereas direct bevacizumab-to-biosimilar treatment was 49.4% less costly than the multistep pathway.

The step-therapy cohort also had the highest injection frequency and the shortest interval extension after transition, findings that may help explain its higher modeled cost. However, the observational study could not establish that payers required a specific number of biosimilar injections or that loading-dose requirements caused the additional costs.

Visual acuity improved across all cohorts, with improvement peaking at approximately 5 months after the first injection before gradually declining. Central subfield thickness decreased across treatment groups. The authors characterized differences in visual acuity as having uncertain clinical significance and concluded that there were minimal clinically significant differences in visual acuity or central subfield thickness among the pathways.

A separate prospective study of 9 US retina practices found that 96.2% of 2225 eligible anti-VEGF prior authorization requests were approved, but 59.6% of the approved requests resulted in a delay in care of more than 24 hours.

 The study also found that the median staff time required to obtain a single authorization was 100 minutes.

Together, the findings suggest that medication transitions involving biosimilars and branded anti-VEGF agents may be associated with longer injection intervals and higher modeled costs, particularly when patients undergo multiple sequential transitions.

 However, the IRIS study was observational, and its economic analysis was a simulation rather than an assessment of actual patient-level costs. The findings therefore do not establish that step therapy itself caused treatment delays, higher costs, or differences in clinical outcomes. The authors called for further research into the clinical and economic consequences of different anti-VEGF treatment pathways before broader step-therapy policies are adopted.

“Given the current use of step therapy mandates and the potential for irreversible vision loss with delays in care, the findings here suggest that multiple transitions can inadvertently promote higher-cost, lower-value approaches than physician-directed care,” wrote the researchers. “The true societal or payer perspective of cost savings will depend on the proportion of patients ultimately requiring multiple transitions, which cannot be determined from this cohort.”

Berkowitz ST, Gilbert JB, Ross CJ, et al. Intravitreal anti-VEGF injection transitions across bevacizumab, biosimilar, and branded medications: the IRIS Registry study. 

. Published online 2026. doi:10.1177/24741264261455206

Dang S, Parke DW, Sodhi GS, et al. Anti-VEGF pharmaceutical prior authorization in retina practices. 

. 2024;142(8):716-721. doi: 10.1001/jamaophthalmol.2024.2217

Articles

Bevacizumab-to-biosimilar-to-branded transitions delayed nAMD care and cost more than direct switches.

Step Therapy to Biosimilars, Branded Anti-VEGF Costs More, Data Show

A systematic review and economic model commissioned by the National Institute for Health and Care Excellence (NICE) and published in 

 found no randomized trials evaluating natalizumab (Tysabri; Biogen) or its biosimilar, natalizumab-sztn (Tyruko; Sandoz), specifically in patients with highly active relapsing-remitting multiple sclerosis (HARRMS).

 The assessment was designed to evaluate these treatments within their marketing authorizations for HARRMS after at least 1 disease-modifying therapy (DMT).

A study found no direct trial evidence for natalizumab or its biosimilar in highly active relapsing-remitting MS and found limited cost-effectiveness vs most alternatives. | Image credit: Sweeann - stock.adobe.com

“Multiple sclerosis is an immune-mediated inflammatory disease, causing long-term disability in young adults,” wrote the researchers of the study. “Most cases begin as relapsing–remitting multiple sclerosis. Some people have a form of relapsing–remitting multiple sclerosis known as highly active relapsing–remitting multiple sclerosis, defined as multiple sclerosis with unchanged or increased disease activity despite prior treatment with at least one disease-modifying therapy.”

HARRMS is broadly defined as relapsing-remitting MS (RRMS) with ongoing disease activity despite treatment with at least 1 DMT. The review noted that the lack of a consensus definition for HARRMS makes it difficult to consistently identify and treat this population. Investigators from the Bristol Technology Assessment Group at the University of Bristol searched MEDLINE, EMBASE, and trial registries through April 2024 and identified 42 studies encompassing 22,409 participants. Most studies enrolled a general RRMS population, while only 2 studies specifically enrolled patients with HARRMS. Four studies evaluated natalizumab or its biosimilar, but none reported HARRMS-specific outcomes for either natalizumab product.

Indirect Comparisons Suggest Similar Efficacy to Comparators

Using network meta-analysis, the authors found no evidence of a difference between natalizumab and its biosimilar in relapse rate (rate ratio, 0.65; 95% credible interval [CrI], 0.34-1.26), gadolinium-enhancing lesions (HR, 1.29; 95% CrI, 0.69-2.37), T2-weighted lesions (HR, 1.07; 95% CrI, 0.73-1.57), any adverse events (HR, 1.06; 95% CrI, 0.77-1.46), or treatment discontinuation (HR, 0.48; 95% CrI, 0.13-1.76) in the general RRMS population.

The HARRMS evidence base was limited to 6 studies covering fingolimod, ocrelizumab, alemtuzumab, cladribine, interferon beta, and autologous hematopoietic stem cell treatment. All interventions except interferon beta-1a reduced relapse risk versus placebo. The analysis also incorporated natalizumab based on a study population considered close to, but not fully meeting, the HARRMS definition. Because of the limited and indirect evidence, the authors emphasized uncertainty about whether treatment effects observed in broader RRMS populations can be extrapolated to HARRMS.

Economic Model Finds Natalizumab Costlier Without a Clear QALY Advantage

To assess cost-effectiveness, the team built a discrete event simulation model using UK MS registry data and willingness-to-pay thresholds of £20,000 and £30,000 per quality-adjusted life-year (QALY), equivalent to approximately $27,000 and $41,000 per QALY, respectively, based on the August 27, 2026, exchange rate. The economic analysis used the UK thresholds; the dollar amounts are provided here for US readers.

With the exception of ocrelizumab, all comparators had greater net benefit than intravenous natalizumab, intravenous natalizumab biosimilar, and subcutaneous natalizumab at the £20,000-to-£30,000/QALY thresholds. The natalizumab products also had close to a 0% probability of having the highest net benefit. Costs were generally higher with natalizumab than with other treatments, while 95% CrIs for QALYs completely overlapped, indicating no evidence of a difference in QALYs. The biosimilar had lower costs and lower QALYs than intravenous originator natalizumab, but the 95% CrIs overlapped.

Compared with ocrelizumab, however, intravenous natalizumab had lower costs and higher QALYs, meaning the model did not favor ocrelizumab over natalizumab on cost-effectiveness. Across the broader comparison, interferon beta-1b and several glatiramer acetate and interferon-based regimens had the greatest modeled net monetary benefit at the £20,000-to-£30,000/QALY thresholds.

A value-of-information analysis found that uncertainty surrounding treatment effects—including network meta-analysis estimates for annualized relapse rate, confirmed disability progression, serious adverse events, and treatment discontinuation—had the greatest impact on the results, although costs, utilities, and MS registry inputs also contributed substantial uncertainty.

The authors concluded that additional trials enrolling patients who meet HARRMS criteria are needed to determine whether natalizumab and its biosimilar perform as expected in this population, rather than relying primarily on extrapolation from broader RRMS trials.

The analysis was limited by the absence of randomized trials directly evaluating natalizumab or its biosimilar in patients meeting the HARRMS criteria, according to the researchers. Much of the evidence was therefore drawn from broader RRMS populations or studies involving populations considered similar to HARRMS, requiring indirect comparisons and extrapolation. The economic model also relied on assumptions about treatment effects, disease progression, costs, utilities, and registry data, contributing to uncertainty around the cost-effectiveness estimates. The authors identified treatment-effect estimates as the largest source of decision uncertainty.

The findings arrive as NICE's companion guidance recommends natalizumab (originator or biosimilar) for rapidly evolving severe RRMS—a narrower subgroup of HARRMS—rather than endorsing use across the full highly active population, with pricing negotiated through a confidential national commercial arrangement.

Overall, the assessment found no direct clinical evidence establishing the comparative effectiveness of natalizumab or its biosimilar specifically in HARRMS.

 Although natalizumab had lower modeled costs and higher QALYs than ocrelizumab, most other comparators had greater net benefit at willingness-to-pay thresholds of approximately $27,000 to $41,000 per QALY. The findings underscore the need for trials specifically enrolling patients with highly active disease to determine whether treatment effects observed in broader RRMS populations can be reliably extrapolated to HARRMS.

“The economic model found that natalizumab and natalizumab biosimilar were not cost-effective compared to any of the included comparators in highly active relapsing-remitting multiple sclerosis, with similar quality-adjusted life-years but higher costs, with the only exception being ocrelizumab,” wrote the researchers. 

Manzano CL, Sadek A, Cooper C, et al. Natalizumab and Tyruko (natalizumab biosimilar) for treating highly active relapsing-remitting multiple sclerosis after at least one disease-modifying therapy: a systematic review and economic model. 

. 2026;30(60):1-290. doi:10.3310/GJHT1811

Natalizumab (originator and biosimilar) for treating highly active relapsing–remitting multiple sclerosis after disease-modifying therapy. National Institute for Health and Care Excellence. Last reviewed January 28, 2026. Accessed August 27, 2026. 

A study found no direct trial evidence for natalizumab or its biosimilar in MS and found limited cost-effectiveness vs most alternatives.

Natalizumab Biosimilar Shows Limited Cost-Effectiveness in MS

Children and young adults with inflammatory bowel disease (IBD) generally maintained stable disease control after an insurance-mandated, nonmedical switch from the adalimumab originator to a biosimilar, according to findings published in 

Most pediatric and young adult patients with IBD maintained stable disease activity and laboratory markers after switching from the adalimumab originator. | Image credit: feng - stock.adobe.com

“Adalimumab biosimilars are as safe and effective compared to the originator. Adult patients with inflammatory bowel disease (IBD) who switched to a biosimilar have comparable outcomes, but pediatric data are limited,” wrote the researchers of the study.

Adalimumab (Humira; AbbVie), an anti–tumor necrosis factor (anti-TNF) biologic, is an established treatment option for pediatric Crohns disease and ulcerative colitis. Infliximab biosimilars have been available in the US since 2016, with established safety and efficacy data in pediatric IBD, and adalimumab biosimilars entered the US market in 2023. Much of the existing evidence has focused on biosimilar-naive patients rather than patients switched from the originator. Ten adalimumab biosimilars had been introduced in the US by June 2024, and payers have increasingly used formulary preferences and step-therapy policies involving adalimumab products.

Researchers at Nationwide Children's Hospital conducted a retrospective chart review of 50 pediatric and young adult patients with IBD who underwent a nonmedical switch from an adalimumab originator to a biosimilar between May 2023 and July 2024.

 The cohort was predominantly male (58%), White (90%), diagnosed with Crohn disease (88%), and covered by commercial insurance (100%). Most patients (92%) were switched to adalimumab-adaz based on payer formularies.

Among the 42 patients with Physician Global Assessment (PGA) data available both before and after the switch, 86% (36 of 42) had stable or improved disease activity. This included 74% who remained in remission and 12% who improved to remission. Six patients (14%) experienced worsening disease activity, although no patients developed severe disease activity. The change in PGA scores before and after the switch was not statistically significant (

Laboratory markers, including albumin, hemoglobin, C-reactive protein, and erythrocyte sedimentation rate, showed no significant differences before and after the switch.

Adalimumab trough levels declined significantly, from a mean of 18.1 µg/mL to 15.0 µg/mL (

= .007). Although levels remained above the 10 µg/mL threshold used by the study authors to define a therapeutic concentration, the decrease may be clinically relevant for some patients, particularly those with perianal disease, for whom higher adalimumab concentrations may be associated with fistula healing.

Detectable antidrug antibodies increased from 4.8% to 14.3% of patients, but the difference did not reach statistical significance (

= .16). Given the small sample size, however, the lack of statistical significance does not necessarily exclude a clinically meaningful change.

Thirty-eight of 50 patients (76%) remained on the biosimilar at least 6 months after the switch. Twelve patients discontinued treatment during follow-up. Five discontinued for reasons considered unrelated to the switch, including insurance changes or persistent baseline disease activity, and the remaining 7 discontinued for reasons considered related to the switch, including adverse effects, disease worsening, or declining drug levels.

The authors also reported that recurrence of symptoms without corresponding biochemical changes could, in some cases, reflect a nocebo effect. This interpretation remains speculative and should not be considered evidence that reported symptoms were not genuine treatment-related events.

The 76% observed 6-month continuation rate was lower than the 93% 6-month durability probability reported in a 2025 European pediatric IBD cohort. However, the populations and study methods differed: the European study include patients initiating a biosimilar and patients switching from the originator, limiting direct comparison between the studies.

The Nationwide Children's study has several limitations. Its retrospective, single-center design; small sample size; predominantly White, commercially insured population; Crohn disease–predominant cohort; and short follow-up limit generalizability. In addition, the absence of a nonswitching control group means the study cannot establish that biosimilar switching is equivalent to continuing the originator product.

“In summary, clinical, laboratory, and pharmacokinetic outcomes were largely maintained over 6 months following a nonmedical switch to adalimumab biosimilars,” wrote the researchers. “While short‐term medication continuation was demonstrated, larger and longer‐term studies are needed to better understand biosimilar use in children—especially as the economic landscape continues to evolve.”

Himelstein D, McNicol M, Abdel-Rasoul M, et al. Outcomes of adalimumab biosimilar nonmedical switches in children and young adults with inflammatory bowel disease. 

. 2026;10.1002/jpr3.70212. doi:10.1002/jpr3.70212

Tesser JRP, Charabaty A, Hebert AA. Switching from adalimumab reference product to and among adalimumab biosimilars outside the USA: insights for US clinicians. 

. 2025;39(4):591-606. doi:10.1007/s40259-025-00719-z

Most pediatric and young adult patients with IBD maintained stable disease activity and laboratory markers after switching from the adalimumab originator. 

Nonmedical Adalimumab Biosimilar Switch Maintains Disease Control in Pediatric IBD

A denosumab (Prolia; Amgen) biosimilar candidate, KN012, demonstrated clinical equivalence to US-reference denosumab for the treatment of postmenopausal osteoporosis (PMO) in a 12-month, double-blind, randomized, active-controlled phase 3 trial conducted across 25 centers in China.

, support KN012 as a viable lower-cost alternative for patients at high fracture risk.

KN012 achieved BMD equivalence with US-approved denosumab in postmenopausal women in China. | Image credit: Art_spiral - stock.adobe.com

“The primary objective was to establish equivalence for the mean percent change from baseline in lumbar spine BMD [bone mineral density] at month 12,” wrote the researchers of the study. “Secondary objectives included assessment of additional efficacy endpoints, safety, bone turnover markers, population pharmacokinetics, and immunogenicity, aiming to provide high-quality evidence for the clinical value and accessibility of a denosumab biosimilar in the Chinese PMO population.”

Trial Design Directly Compared Biosimilar With Reference Product

Denosumab, a fully human monoclonal antibody that targets RANKL, inhibits osteoclast-mediated bone resorption and has been a mainstay PMO therapy since the pivotal FREEDOM (

) trial demonstrated reductions in vertebral and nonvertebral fracture risk. Despite its established efficacy, cost has remained a persistent barrier to access, prompting biosimilar development efforts worldwide.

The study enrolled 279 Chinese women aged 50 to 80 years with a T-score between −2.5 and −4.0 at the total hip or lumbar spine, plus at least one additional fracture risk factor. Participants were randomized 1:1 to receive 60 mg of KN012 or US-denosumab subcutaneously at baseline and month 6, with all patients also receiving daily calcium and vitamin D supplementation. Unlike 2 earlier Chinese denosumab biosimilar trials that used placebo controls, this study was the first head-to-head, active-controlled comparison against the reference product in this population, a design intended to yield more direct equivalence evidence.

Primary End Point Met With Narrow Margins

The primary efficacy analysis indicated that the least squares mean difference between the KN012 group and the US-denosumab group was 0.22% (95% CI, −0.78, 1.23) in the full analysis set and 0.11% (95% CI, −0.92, 1.14) in the per-protocol set. Both confidence intervals fell entirely within the predefined equivalence margin (±1.75%), confirming clinical equivalence between KN012 and US-denosumab. Secondary efficacy end points, safety, bone turnover markers, population pharmacokinetics, and immunogenicity results were comparable between the 2 groups up to month 12.

Secondary bone mineral density end points at the total hip, femoral neck, and trochanter also improved similarly in both arms, and bone turnover markers (s-CTX and P1NP) followed comparable suppression-and-recovery patterns across the dosing interval.

Safety and Immunogenicity Profiles Were Comparable

Treatment-emergent adverse events occurred in 85.7% of the KN012 group and 86.3% of the US-denosumab group. Adverse drug reactions—most commonly hypocalcemia, hypophosphatemia, and urinary tract infection—occurred at similar rates, and all were grade 1 or 2. Serious adverse events were reported in 8.6% of the KN012 group vs 13.7% of the reference group, with no events attributed to the study drug except a single case of liver enzyme elevation in the US-denosumab arm, later judged unrelated to treatment. No cases of osteonecrosis of the jaw, atypical femoral fracture, or serious infection—risks flagged in the denosumab label—were observed in either arm.

Immunogenicity was low across both products. By month 12, no KN012 recipients tested positive for anti-drug antibodies, compared with 2.3% of US-denosumab recipients; no neutralizing antibodies were detected in either group at any time point. 

Biologic pricing has long constrained broader use of denosumab despite its favorable long-term benefit-risk profile, and biosimilars are positioned to expand access without compromising outcomes.

 In the US, where multiple denosumab biosimilars have launched following FDA approval, payer modeling has projected measurable savings from conversion: one recent analysis estimated per-member-per-month savings of $0.59 under a base-case scenario assuming majority conversion to biosimilars for osteoporosis and oncology indications within 5 years. As additional denosumab biosimilars like KN012 generate further equivalence data, managed care organizations may find further support for formulary strategies favoring biosimilar-first approaches, potentially easing cost barriers for patients at high fracture risk while preserving the clinical benefits associated with RANKL inhibition.

“Comparable efficacy in terms of bone mineral density gains, along with similar safety and pharmacokinetic profiles, was observed between the 2 treatments,” wrote the researchers.

The study employed a parallel-group design without crossover. These findings collectively support KN012 as a well-tolerated and effective biosimilar alternative in this patient population.”

Zhu X, Liu J, Mao Y, et al. Comparison of KN012, a denosumab biosimilar, versus reference denosumab in Chinese postmenopausal women with osteoporosis: efficacy, safety, and population pharmacokinetics in a 12-month phase III study. 

. 2026;29:101916. doi:10.1016/j.bonr.2026.101916

Myshko D. Biosimilar denosumab could save $0.59 per member per month. 

December 3, 2025. Accessed July 31, 2026. 

https://www.managedhealthcareexecutive.com/view/biosimilar-denosumab-could-save-0-59-per-member-per-month

KN012 achieved BMD equivalence with US-approved denosumab in postmenopausal women in China. 

Denosumab Biosimilar KN012 Matches Reference Drug in Phase 3 Osteoporosis Trial

Long-term treatment with an eculizumab biosimilar (Elizaria; Generium) produced stable hematologic and safety outcomes in patients with atypical hemolytic uremic syndrome (aHUS), according to the results of a prospective, multicenter observational study published in 

A 50-patient study found sustained platelet recovery and low TMA rates through 52 weeks of biosimilar therapy, with a favorable safety profile. | Image credit: สัมฤทธิ์ ไกรยนุช - stock.adobe.com

“The objective of a multicenter, prospective, observational study of an eculizumab biosimilar (Elizaria) was to analyze the efficacy and safety of long-term complement inhibitor therapy in patients with atypical hemolytic uremic syndrome (aHUS),” wrote the researchers of the study.

aHUS is a rare, life-threatening form of thrombotic microangiopathy (TMA) driven by uncontrolled activation of the complement alternative pathway, leading to microvascular thrombosis, hemolytic anemia, and progressive kidney injury.

 Without treatment, the condition carries a high risk of end-stage kidney disease and death. Terminal complement inhibition with eculizumab has been standard of care for more than a decade, transforming aHUS from a frequently fatal diagnosis into a manageable chronic condition. However, the reference product's cost has limited access in many health systems, spurring development of biosimilars intended to expand access while preserving efficacy and safety.

Consistent Efficacy Across Age Groups and Treatment Histories

The observational study enrolled 50 patients with aHUS aged 1 to 55 years, 42% of whom were under age 18.

 Patients received the eculizumab biosimilar in routine clinical practice over 56 weeks. Nineteen patients (38%) had previously been treated with reference eculizumab before enrolling, while 31 (62%) were naive to complement inhibitor therapy.

By the end of the study, mean (SD) platelet counts rose by 39.48 (21.7) × 10

/L in treatment-naive patients and 33.61 (24.06) × 10

/L in treatment-experienced patients. Nearly all patients achieved normal platelet counts—100% of treatment-naive patients and 96% of treatment-experienced patients. Mean lactate dehydrogenase activity, a marker of hemolysis, remained essentially unchanged, from 253.84 (122.22) U/L at screening to 245.24 (93.52) U/L at the end of the study, indicating that hemolytic activity was already controlled and stayed controlled.

63 Unrelated Adverse Events, Low Immunogenicity Reported

Investigators reported 63 adverse events judged unrelated to the biosimilar during the safety assessment period. No details on serious adverse events or discontinuations attributable to the study drug were disclosed in the published abstract. The authors characterized the overall safety profile as favorable, with low immunogenicity observed over the treatment course, a notable finding given ongoing concerns among clinicians about antidrug antibody formation with long-term biologic switching in rare disease populations.

Freedom from TMA events was reported in 77.6% of patients at week 21 and 80% at week 52. The proportion of patients achieving a complete TMA response increased significantly over the study period, reaching 8% (

= .046). Renal function also improved for a subset of patients: 12% had an estimated glomerular filtration rate gain of at least 15 mL/min/1.73 m

The stability of platelet counts and TMA response rates across both treatment-naive and switch populations may support formulary strategies that favor biosimilar initiation or transition for eligible patients, provided ongoing pharmacovigilance continues to confirm low immunogenicity. As more eculizumab biosimilars gain global approval, comparative real-world evidence like this study will be important for utilization management decisions and prior authorization criteria in rare disease programs.

“Long-term complement inhibitor therapy with the eculizumab biosimilar in patients with aHUS has demonstrated a stable effect, a favorable safety profile, and low immunogenicity,” wrote the researchers. 

Kotenko O, Kozlovskaya N, Emirova K, et al. Long-term therapy with eculizumab biosimilar in patients with atypical haemolytic uraemic syndrome: outcomes of a prospective observational study. 

. Published online June 12, 2026. doi:10.1159/000552914

Campbell P. FDA approves first interchangeable biosimilar to eculizumab for PNH and aHUS. 

https://www.hcplive.com/view/fda-approves-first-interchangeable-biosimilar-to-eculizumab-for-pnh-and-ahus

A 50-patient study found sustained platelet recovery and low thrombotic microangiopathy rates through 52 weeks of biosimilar therapy, with favorable safety.

Eculizumab Biosimilar Shows Durable Benefit in Long-Term aHUS

Aflibercept 2 mg biosimilar SB15 (Afilivu; Samsung Bioepis) produced significant anatomical improvements and stable visual acuity across multiple retinal diseases, supporting its effectiveness and safety in both treatment-naïve and biosimilar-switching patient populations.¹

This large, multicenter, retrospective real-world study conducted in South Korea is published in 

Aflibercept biosimilar SB15 improved retinal anatomy while preserving vision in both treatment-naive and switching patients with nAMD, RVO, and DME. | Image Credit: Orawan - stock.adobe.com

Evaluating Biosimilars Across a Broad Real-World Retinal Population

Biosimilars have become an increasingly important lever for expanding access to anti–vascular endothelial growth factor (VEGF) therapy amid the substantial treatment burden of chronic intravitreal injections. The AURA Korea study, conducted across 3 South Korean tertiary centers, evaluated outcomes among 1083 eyes from 984 patients who received a total of 2762 injections of SB15 between March 2023 and February 2025. The cohort included 188 treatment-naïve eyes (17.4%) and 895 eyes switched from another anti-VEGF agent (82.6%), spanning neovascular age-related macular degeneration (nAMD, n = 611), retinal vein occlusion (RVO, n = 182), diabetic macular edema (DME, n = 173), and other retinal conditions (n = 117). 

Anatomical Gains Held Across Diagnoses, With Vision Preserved

Over a mean (SD) follow-up of 5.17 (2.76) months and 2.55 (1.09) injections per eye, central foveal thickness decreased significantly by −47.5 µm (95% CI, −55.2 to −39.8; 

 < .001), while best-corrected visual acuity (BCVA) remained stable (mean change, −0.003 

 = .572). Treatment-naïve eyes showed greater anatomical improvement than switching eyes (−93.9 µm vs −37.9 µm; 

Retinal fluid resolution was significant across all 3 major diagnostic groups: subretinal fluid in nAMD decreased from 51.2% to 29.6% (

< .001), intraretinal fluid in RVO fell from 92.9% to 76.4% (

 < .001), and intraretinal fluid in DME declined from 90.8% to 84.4% (

 = .002). Safety findings were reassuring, with only 1 case (0.09%) of rhegmatogenous retinal detachment and no episodes of intraocular inflammation or other serious adverse events reported.

These findings are broadly consistent with other real-world switching data in retinal disease. A United Kingdoom study of patients switched to high-dose aflibercept after treatment-refractory nAMD similarly found stable visual acuity alongside anatomical improvement, reinforcing that switching anti-VEGF regimens—whether to a biosimilar or a reformulated originator—can maintain disease control without compromising outcomes.

“Switching to aflibercept 8 mg in treatment-refractory nAMD eyes in a real-world setting was associated with increased treatment durability, modest anatomical improvements, stable BCVA, and a favorable short-term safety profile,” wrote the researchers of the UK study. “These early outcomes support the use of aflibercept 8 mg in eyes with high treatment burden and persistent disease activity within routine clinical practice. Importantly, no serious ocular adverse events were observed despite the higher injection volume compared to conventional anti-VEGF agents. Further prospective studies with larger sample sizes and longer follow-up are warranted to confirm the long-term efficacy, durability, and safety of aflibercept 8 mg.”

For payers and health systems, these findings offer real-world reassurance that switching established patients to the aflibercept biosimilar SB15 is unlikely to compromise anatomical or visual outcomes across the most common retinal indications, supporting formulary strategies that favor biosimilar adoption to reduce per-injection costs. The low serious adverse event rate further supports confidence in safety-driven step therapy or mandatory-switch policies, although plans should continue to monitor longer-term durability data, as follow-up in this cohort was limited to roughly 5 months.

“These findings support the real-world effectiveness and safety of SB15 (Afilivu) in both treatment-naïve and switching populations across diverse retinal diseases,” wrote the researchers of the study. 

Song JR, Jeon J, Baek SC, et al; International Retina Biosimilar Study Group (Inter BIOS Group). Aflibercept biosimilar use and real-world outcomes in various retinal diseases: the AURA Korea study. 

Musadiq M, Musadiq M, Latif F, et al. Early real-world outcomes of switching to 8 mg aflibercept for neovascular age-related macular degeneration in the United Kingdom. 

. 2025;15(6):903. doi:10.3390/life15060903

Aflibercept biosimilar SB15 improved retinal anatomy while preserving vision in both treatment-naïve and switching patients with nAMD, RVO, and DME.

Aflibercept Biosimilar SB15 Shows Real-World Efficacy Across Retinal Diseases

A multicenter retrospective study spanning nearly 5000 eyes across 5 tertiary eye-care centers in India has added substantial real-world weight to the case that biosimilar ranibizumab can serve as a viable, lower-cost alternative to the innovator drug for treating a range of vision-threatening retinal conditions.

Nearly 5000 eyes and nearly 21,000 injections show comparable vision, anatomical, and safety outcomes between Ranieyes and Lucentis/Accentrix. | Image credit: Viktor - stock.adobe.com

“Much of the available evidence is disease-specific, noncomparative, or limited by relatively short follow-up,” wrote the researchers of the study. “In addition, fewer multicenter real-world studies have evaluated a single ranibizumab biosimilar brand against innovator ranibizumab across heterogeneous retinal vascular diseases while simultaneously examining longitudinal outcomes, treatment burden, and safety. This gap provided the rationale for the present study.”

The study compared outcomes between biosimilar ranibizumab (Ranieyes; Lupin Pharmaceuticals) and innovator ranibizumab (Lucentis/Accentrix; Novartis) in 4997 eyes from 3577 patients treated between July 2022 and October 2025. The biosimilar arm included 2543 eyes (10,893 injections), while the innovator arm included 2454 eyes (10,136 injections). Patients were treated for neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), branch and central retinal vein occlusion (BRVO/CRVO), myopic choroidal neovascularization (mCNV), and an exploratory group receiving anti-VEGF therapy as a preoperative adjunct before vitreoretinal surgery.

Comparable Vision and Anatomical Outcomes

Across nearly all disease categories, both drugs produced a similar pattern: rapid improvement in best-corrected visual acuity (BCVA) and reduction in central subfield thickness within the first 3 months, followed by long-term stabilization through 24 months. In DME, BRVO, CRVO, and mCNV, the visual acuity trajectories of the 2 groups tracked closely together at every follow-up visit. The nAMD subgroup showed 1 statistically notable gap—a slightly better BCVA in the biosimilar group at 12 months—but the researchers noted the difference was small in magnitude and did not persist at 18 or 24 months, making it unlikely to reflect a true clinical distinction between the drugs.

The number of injections needed over the study period was nearly identical between groups for DME, nAMD, and CRVO. Small but statistically significant differences emerged in BRVO and mCNV, although the researchers cautioned that real-world retreatment decisions are shaped by cost, logistics, and physician judgment rather than a fixed protocol, so these gaps should not be overinterpreted.

Across more than 21,000 total injections, serious complications were rare in both arms. Endophthalmitis, the most feared injection-related complication, occurred in only 1 of 10,893 biosimilar injections vs 2 of 10,136 innovator injections—a difference with no statistical significance. Rates of retinal pigment epithelial tears, intraocular inflammation, and serious systemic vascular events such as myocardial infarction and stroke were also similar between groups, and the authors reported no new safety signal for the biosimilar.

The economic case is central to the study's relevance. At the participating Indian hospitals, innovator ranibizumab cost roughly $270 to $325 per injection compared with about $129 to $173 for the biosimilar—a discount that could meaningfully affect treatment continuity in settings where repeated injections over years strain patient budgets. Because retinal vascular diseases are chronic and relapsing, requiring long-term anti–vascular endothelial growth factor therapy, affordability directly affects whether patients keep up with the injection schedules needed to preserve vision.

This Indian cohort adds to a growing body of real-world data on ranibizumab biosimilars internationally. A related multicenter study in South Korea, the ROSE Korea study, evaluated 2 regulatory-approved biosimilars—Amelivu and LucenBS—and similarly found outcomes broadly comparable to reference ranibizumab, while noting that such biosimilars generally offer a 20% to 30% cost reduction compared with the originator product.

Together, these studies suggest that as more ranibizumab biosimilars clear regulatory bars around the world, clinicians are accumulating the kind of large-scale, real-world reassurance that tends to drive broader adoption—provided prescribers keep in mind that each biosimilar brand still needs its own body of evidence, since findings from one product don't automatically transfer to another.

“These findings should be interpreted as supportive observational comparative evidence rather than formal proof of equivalence,” wrote the researchers.

“Because this study evaluated a single biosimilar brand, the results should not be generalized to all ranibizumab biosimilars. Further adjusted, disease-specific multicenter comparative studies across different biosimilar brands are warranted.”

Chakraborty D, Sinha TK, Sinha S, et al. Real-world comparison of biosimilar ranibizumab (Ranieyes) and innovator ranibizumab (Lucentis/Accentrix) across multiple retinal vascular diseases (the BRIO study). 

Song JR, Park UC, Lee CS, et al. Real-world outcomes of ranibizumab biosimilars in various retinal diseases: a Korean multi-center experience-ROSE Korea Study. 

. 2026;16(1):4220. doi:10.1038/s41598-025-34325-4

Nearly 5000 eyes and nearly 21,000 injections show comparable vision, anatomical, and safety outcomes between biosimilar ranibizumab and the innovator drug.

Biosimilar Ranibizumab Performs on Par With Innovator Drug Across Retinal Diseases

Ryan Haumschild, PharmD, MS, MBA, director of pharmacy services at Emory Healthcare and Winship Cancer Institute, provides an overview of biosimilars in the breast cancer space and lingering adoption barriers for oncology biosimilars.

Haumschild's comments came at the end of Breast Cancer Awareness Month and the beginning of Global Biosimilars Week, an annual biosimilar awareness campaign hosted by the International Generic and Biosimilar Medicines Association.

With October being Breast Cancer Awareness Month, what more is needed from providers and health systems to ensure patients have adequate access to biosimilars for breast cancer?

I think access to biosimilars is really important. It drives down the cost of care and I think allows more patients to be on treatment. But there's still some unanswered questions that exist. How do we get these biosimilars implemented into our EMR [electronic medical record]? What happens when some biosimilars are no longer covered by payers and we still want to utilize them? How quickly can we change a lot of our order sets? 

And then again, how do we educate some patients that might be concerned. They might be in curative intent. Do we have the proper education to make sure that patients understand that biosimilars are equivalent to the reference product and still provide great outcomes for them? Especially in their cancer journey for breast cancer. [We need to] let them know that they might interact with biosimilars throughout a variety of different treatment options, and they're still going to give durable responses.

I think once we get that education out, learn how to implement these biosimilars in a timely manner, we'll be a lot more successful, specifically in our breast cancer population.

What role can biosimilars for breast cancer play in improving breast cancer treatments overall?

I think biosimilars, again, will continue to provide more treatment options for patients at a lower cost. And I think that's a great thing. I think when you're creating more equitable access—you think about diversity, equity, inclusion in breast cancer—there's still a lot that we have left to accomplish. And so if we can leverage biosimilars, whether in combination or for supportive care, more patients can get on treatment or reducing the cost of the care to the provider. That's a great thing. 

When we think about value based care of breast cancer, we think about EOM [Enhancing Oncology Model] and some of those value-based care models, the more that we can leverage biosimilars and those frameworks. I think if we make more sustainable models of care, we can bring care out to the community or to patients directly

Also, can we consider [biosimilars for] home infusion or supportive care medications that patients can take at home? I think the more we can do that, and the more we make accessibility one of the key drivers, I think that's going to create better uptake for breast cancer patients as a whole and I think that's something to get excited about.

Studies have shown that oncology and supportive care biosimilars are the biosimilars with the highest market share and providers are very comfortable using these products. What are some of the main challenges still facing oncology biosimilars?

Biosimilars have good uptake now and I think there's a lot of excitement. Actually, I think oncology and maybe breast oncologist are one of the main leaders in adopting these therapies. But I think as we start to utilize them, we're seeing a little bit more difficulties, sometimes from the reimbursement side. So, if you look at net cost recover—if you're a large community oncology practice or health system—the average sales price continues to trend downward. And unfortunately, that's really difficult because that's the reimbursement for a lot of these practices. If there's no margin, there can always be the same mission. 

I think at the same regard, when we're utilizing these therapies, how many denials are we getting from our payer colleagues because we're not using the preferred biosimilar? And there's that slow down time to treatment. And when I think about breast cancer patients, we're really thinking about overall survival and progression free survival. So, every day and every minute counts for how quickly we can get them started on treatment. And the more we see delays there, I think that also influences treatment. 

Lastly, biosimilar uptake is important, but now we're seeing the reference products being reformulated to subcutaneous products. And so I think subcutaneous and a faster infusion sometimes might be more warranted, and then also kind of limits the growth of biosimilars into some of those therapeutic areas.

Videos

Ryan Haumschild, PharmD, MS, MBA, director of pharmacy services at Emory Healthcare and Winship Cancer Institute, discusses the growth and continued challenges facing biosimilars used to treat breast cancer.

Dr Ryan Haumschild Draws Link Between Biosimilars, Health Equity in Breast Cancer

With the volume of new biosimilars coming to the market, there will be many challenges to specialty pharmacies will need to consider when handling these drugs that are unique from generic drugs, says Fran Gregory, PharmD, vice president of emerging therapies at Cardinal Health.

What strategies can specialty pharmacies implement to effectively manage the handling of biosimilars, which may have unique requirements compared with traditional generic medications?

Yes, the inventory management is something I have heard a lot of concern about with biosimilars from specialty pharmacies in particular, and retail pharmacies when we think about the insulins coming to market and the vast number of biosimilars that will come to market for 1 reference product. If in your pharmacy you have 20 boxes of Humira on your shelf, you're now going to have 20 × 10 different rows of Humira biosimilars on your shelf; that gets overwhelming to think about from a sheer capacity and volume and storage requirements. How many more refrigerators am I going to need to buy very tactical things that manufacturers might not be thinking about, or the FDA might not have been thinking about when we created these approval pathways and designations? Specialty pharmacies are hopefully preparing and planning for the launch of these multiple biosimilars.

Because it is a different world that we're coming into and the way that formularies will choose their biosimilar of choice, they will be challenged to maintain significantly larger volume of inventory more likely than they may have previously. I think the other piece of that is having a really good in-time inventory supplier. So, making sure that you have a supplier that can ship your medications overnight when you need them so your patients aren't waiting; so that you don't have any out-of-stock medications, and just making sure that you really manage your inventory, maybe much more closely than you would maybe think you would have to bet the reference product.

Fran Gregory, PharmD, vice president of emerging therapies at Cardinal Health, discusses how specialty pharmacists manage inventory, storage, and handling of biosimilars. 

Dr Fran Gregory Discusses the Unique Requirements for Handling Biosimilars

Knowing that a specific biosimilar will produce the same clinically signficant response as the branded medication is key to ensuring comfortabiltiy among patients and providers, says Fran Gregory, PharmD, vice president of emerging therapies at Cardinal Health. 

How can healthcare providers, pharmacists, and payers collaborate to ensure that patients have access to high-quality biosimilars and make informed decisions about their use in their treatment plans?

I think a lot of that goes back to educating the entire line of stakeholders, from the providers, from the pharmacists to the nurses administering it, the technicians in the pharmacy, all the way to the patient and their caregivers. Making sure that all those stakeholders are confident that this medication is clinically the same product, that they're going to have the same clinical benefits, they're not going to have different adverse events, they’re not going to develop immunogenicity. Creating confidence and a comfort level across every single one of those stakeholders is really a key piece to making sure that patients get access to these medications.

There have been a number of surveys where it is found that most providers are willing to prescribe a biosimilar. I think about 70% of patients say they would be happy to take a biosimilar if their health care providers reassured them with confidence that it was the same product, and they would get the same clinical response. So, it's really that reassuring of the patient that this is a good thing to do and, ultimately, will save the US health care system dollars and, hopefully, it will also save the patient money as well.

Fran Gregory, PharmD, vice president of emerging therapies at Cardinal Health, discusses the importance of collaboration between all stakeholders to boost confidence in providing patients with a biosimilar drug. 

