Tony Hagen is senior managing editor for The Center for Biosimilars

Same-day vs next-day administration of pegfilgrastim as prophylaxis against febrile neutropenia (FN) in patients undergoing myelosuppressive chemotherapy (CTX) shows promise despite preexisting concerns this may increase the incidence of FN, investigators reported in studies of patients with lung and breast cancer presented at the ASCO 2021 Annual Meeting.

With the savings biosimilars afford and in a country emerging from the COVID-19 pandemic, same-day treatment appears to make economic and practical sense, they said.

Findings from a retrospective study at the University of Arizona suggest that for patients with lung cancer, same day treatment with pegfilgrastim “provides a unique opportunity for cancer care without concerns for FN,” investigators wrote.

Guidelines suggest that pegfilgrastim be administered 24 hours after myelosuppressive chemotherapy (CTX), and data from previous studies had not clarified the utility of same-day vs next-day pegfilgrastim use for this class of patients, they said.

They included 114 patients who met the inclusion criteria; 76% (n = 87) of patients had non–small cell lung cancer and 24% (27) had small cell lung cancer. Of those, 52% had stage III/IV cancer and 63% had ECOG status of 0 to 1.

Study authors said 72% of patients had mild FN risk, mean standard deviation absolute neutrophil count at baseline was 5.68, and 384 CTX cycles were received in total.

One patient developed FN after the first cycle of CTX of irinotecan and, across all cycles, 5 patients developed 6 FN episodes.

Two of those patients were on carboplatin etoposide, 1 was on cisplatin etoposide, and 1 on vinorelbine. For the patient who experienced 2 episodes of FN, these occcured following a switch from pemetrexed to irinotecan CTX.

Vraney J, AlRawashdh N, Choi B, Abraham I, McBride A. An institutional evaluation of the safety and efficacy of same-day administration of pegfilgrastim in patients receiving chemotherapy for lung cancer. Presented at: ASCO 2021: June 3-7, 2021. Abstract e18591

In patients with breast cancer, pegfilgrastim biosimilar (Udenyca) administered as prophylaxis for FN on the same day as CTX appears to be safe and effective, investigators wrote. “Previous literature has indicated that pegfilgrastim administration prior to 24 hours post chemotherapy may result in a deepened and prolonged neutropenia due to the increase in circulating granulocytes exposed to chemotherapy.”

Oncologists at Inova Schar Cancer Institute in Fairfax, Virginia, conducted a retrospective chart review of 55 patients treated by 4 medical oncologists in the center’s breast cancer group. They said 16.4% of patients experienced grade 3/4 FN and 10.9% (n = 6) were hospitalized. There were no grade 5 events and FN was not the cause of therapy discontinuation for any of the patients. “Of note, there were no cases of COVID-19 among the 9 patients who had an episode of FN.”

They said 94.5% (n = 52) of patients included in the study received treatment with curative intent and 5.5% (n = 3) had metastatic disease in subsequent lines of therapy.

“Same day pegfilgrastim-cbqv appears to be a safe and effective option in the primary and secondary prophylaxis of FN with myelosuppressive standard of care chemotherapy used in breast cancer treatment,” they concluded.

They cautioned that their study was confined to a relatively small sample of patients and a young age group (median age, 49.1).

“This opens the door to further re-evaluation of same day [Udenyca] administration in other patient populations. In a postpandemic treatment world, this slight change in practice has the potential to reduce patient financial toxicity associated with multiple medical visits, provide an alternative to on-body injector formulations, and ensure treatment adherence,” they said.

Leiva M, Pennisi A, Kiernan Harnden K, Rizzo PC, Mauro LA. The feasibility of same day pegfilgrastim-cbqv administration in breast cancer patients receiving myelosuppressive chemotherapy regimens at a northern Virginia cancer center. Presented at: ASCO 2021: June 3-7, 2021. Abstract e18687

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ASCO

Same-day pegfilgrastim to combat febrile neutropenia in conjunction with myelosuppressive chemotherapy (CTX) is safe, investigators conclude. 

Investigators: Same-Day Pegfilgrastim Is Safe and Effective in Patients Receiving CTX for Breast, Lung Cancer

Celltrion Healthcare reported positive findings from a European Union real-world 

 comparing the company’s rituximab biosimilar (CT-P10, Truxima) with the reference product (Rituxan) in patients with diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma (NHL). Results were reported at the European Hematology Association 2021 Virtual Congress.

Celltrion also released real-world data demonstrating comparable safety and effectiveness of CT-P10 rapid infusion.

CT-P10 treatment data were collected during a 30-month observation period. Primary end points included overall survival (OS) and progression-free survival (PFS), and secondary end points included safety profile and CT-P10 treatment pathways.

At the 30-month point, OS was 74% (95% CI, 69.2%-79.1%) and PFS was 67% (95% CI, 61.3%-72.1%) among patients (N = 382) undergoing first-line treatment with CT-P10.

Among enrollees, a complete response (CR) was observed in 82% (n = 312); partial response (PR), 12% (n = 46); no response or stable disease 4% (n = 16); and progressive disease, 2% (n = 8).

CT-P10 tolerability also was reported to be comparable to the reference product. The investigators said 90% (n = 351) of patients reported 1 or more adverse events (AEs), 65% (n = 253) experienced a grade 3 or higher event, and 28% of AEs were reported as “definitely, probably, or possibly related to CT-P10.”

“This is the first multicountry retrospective postapproval study to investigate the effectiveness and safety of CT-P10 treatment in patients with DLBCL in a real-world setting across Europe,” said Mark Bishton, MD, consultant hematologist and a clinical associate professor at the University of Nottingham, School of Medicine, England.

The European Medicines Agency approved CT-P10 for treatment of rheumatoid arthritis and certain blood cancers, including NHL, in 2017. DLBCL accounts for an estimated 30% to 40% of NHL incidence.

“The response rates, survival rates and overall safety profile for CT-P10 appear consistent with those reported for reference rituximab, which could support the use of CT-P10 in combination with chemotherapy as a therapeutic option for DLBCL,” authors of the study wrote.

Discussing the second study, the investigators said rapid infusion of CT-P10 was generally well tolerated, with 10% (n = 20; 95% CI, 6%-15%) of patients experiencing infusion-related reactions (IRRs).

“We are encouraged by the results of the study, as CT-P10 has demonstrated a similar IRR rate to reference rituximab,” said HoUng Kim, PhD, head of the Medical and Marketing Division of Celltrion.

The investigators said most IRRs were grade 1/2 (96%), and the most common of these were fatigue (35%), nausea (30%), and vomiting (15%). Patients achieving CRs and PRs over 6 months of observation were 74% and 22%, respectively.

“The recommended protocol for rituximab infusion in Europe is a slow initial infusion rate with a gradual upward titration. Rapid infusion is often used in subsequent infusions for patients who had no serious complications related to the first infusion,” Kim said.

Postmarketing retrospective studies of the rituximab biosimilar (CT-P10, Truxima) demonstrated comparable safety and efficacy for treatment of diffuse large B-cell lymphoma (DLBCL).

Celltrion Reports Positive Real-World Findings for Truxima in DLBCL

The Oncology Care Model (OCM), begun in 2016 by CMS to promote value-based care over costly “buy and bill” pharmacy practices, has “led to reduced use of some high-cost supportive care medications, with patterns suggesting more value-conscious care,” according to findings presented at ASCO 2021.

Alternative payment models have potential to drive value-based changes in medication use during cancer care.

Investigators sourced Medicare claims from 2013 to 2019 in an evaluation of outpatient supportive care medication use during chemotherapy treatment at practices participating in the OCM or in “propensity-matched comparison practices,” used as an artificial cohort.

Except for a filgrastim biosimilar analysis, where the adoption trend was assessed, the investigators used a differences-in-differences (DID) statistical method to compare findings between cohorts.

The OCM had no effect on the use of any type of bone supportive medication (denosumab or bisphosphonate) among patients with metastasized bone cancer; however, it did result in lower use of denosumab in patients with breast cancer (DID = –5.0 percentage points; 90% CI, –7.1 to –2.8), prostate cancer (DID = –4.0 percentage points; 90% CI, –5.9 to –2.2), and lung cancer (DID = –4.1 percentage points; 90% CI, –7.4 to –0.9).

The OCM resulted in lower use of neurokinin-1 (NK1) antagonists and serotonin antagonists in patients who were starting chemotherapy with high or moderate emetic risk, according to the authors. This included a 6-percentage-point reduction in use of NK1 antagonists for patients undergoing high–emetic risk chemotherapy (90% CI, –9.0 to –3.1), as opposed to no effect on antiemetic use during low–emetic risk chemotherapy.

No change was noted in use of prophylactic white blood cell growth factors among patients receiving chemotherapy with high risk for febrile neutropenia (FN).

A 7.6-percentage-point reduction in prophylactic granulocyte colony stimulating factor (G-CSF) was observed for patients with breast cancer receiving chemotherapy with intermediate risk for FN (90% CI, –12.6 to –2.7). Conversely, no change in prophylactic G-CSF use was observed for patients with lung or colorectal cancer.

The OCM resulted in faster adoption of filgrastim biosimilar vs originator product for patients treated with this agent (differential trend estimate, 2.6%; 90% CI, 1.0%-4.4%).

“Alternative payment models have potential to drive value-based changes in medication use during cancer care,” the authors concluded.

Brooks GA, Landrum MB, Kapadia NS, et al. Impact of the Oncology Care Model on use of bone supportive medications, antiemetics, and growth factors. Presented at: ASCO 2021: June 3-7, 2021. Abstract 1517. 

Investigators noted a reduction in use of high-cost supportive care agents, suggesting that the value-based Oncology Care Model (OCM) is working. 

Study: OCM Reduces Use of Some Supportive Care Medications and Boosts Filgrastim Biosimilar Use

Investigators in Alberta, Canada, said no significant differences in pathologic complete response rates (pCRs) were observed in a study of patients with human epidermal growth factor receptor 2–positive (HER2+) treated with the biosimilar trastuzumab Ogivri vs the originator product, Herceptin.

pCR rates were similar for patients treated with [Ogivri] compared with [Herceptin] in our real-world study of HER2+ neoadjuvant [early breast cancer] and comparable to pivotal phase 3 trials.

The study authors postulated that although biosimilars are certified as having no clinically meaningful differences from originator products, there is potential for clinically meaningful differences in outcomes because biosimilar manufacturers must produce new cell lines to replicate originator biologics and are not given access to the originator cell lines.

Concerns about “this inherent alteration in production” are settled through phase 1 pharmacokinetic and pharmacodynamic comparative studies and phase 3 studies to demonstrate biosimilar equivalency in patients for at least 1 indication of the originator product, investigators said.

Prior confirmatory studies have evaluated the biosimilarity of Ogivri and Herceptin in the metastatic HER2+ setting. In this study, investigators sought to elucidate biosimilar equivalence in the neoadjuvant, or early breast cancer (EBC), setting.

The study enrolled patients (N = 136; 56% originator, 43% biosimilar) treated with trastuzumab originator from November 2018 to October 2019 and the biosimilar from December 2019 to September 2020. There was no crossover between products. Investigators used logistic regression to control for factors that might affect pCR in either cohort, such as biosimilar or originator agent, age, tumor type, node positivity, tumor grade, hormone receptor status, treatment with chemotherapy, and whether chemotherapy treatment was completed.

Based on the logistic regression model, investigators saw no significant difference in pCR odds for patients treated with biosimilar vs originator (odds ratio [OR], 1.1; 95% CI, 0.5-2.4; 

 = .85). However, there was a statistically insignificant lower likelihood of pCR in patients with anthracycline use (OR, 0.72; 95% CI, 0.3-1.6; 

Investigators observed no significant differences in baseline characteristics among patients except the proportion of those with node negative results: 39%, biosimilar; 14.3%, originator (

 = .001). For patients treated with biosimilar vs originator, pCR was a nonstatistically significant 35.6% vs 40.3%, respectively (

“pCR rates were similar for patients treated with [Ogivri] compared with [Herceptin] in our real-world study of HER2+ neoadjuvant EBC and comparable to pivotal phase 3 trials,” the authors concluded.

Yang C, Khwaja R, King K, et al. Trastuzumab-dkst versus trastuzumab: real-world pCR rates in patients with HER2+ breast cancer treated with neoadjuvant chemotherapy plus trastuzumab from Alberta, Canada. Presented at: ASCO 2021; June 3-7, 2021. Abstract e12569.

Investigators further elucidate the equivalence of a trastuzumab biosimilar vs Herceptin in human epidermal growth factor receptor 2–positive (HER2+) breast cancer. 

Ogivri Equivalence Demonstrated in Neoadjuvant HER2+ Comparative Trial

Eleven biosimilars for use in oncology have been launched since the start of 2019, and investigators who sought to measure oncologists’ response to these agents reported initial hesitation, followed by robust uptake and hefty savings.

They noted that the biosimilar competition had little effect on reference product prices, which “remained stable.”

We conclude that uptake of biosimilars among oncology providers between 2019-2020 was rapid, although the extent of biosimilar prescribing varied among products. Biosimilars offered greatly reduced costs to providers, although reference product prices remained stable despite increased biosimilar competition.

The findings were reported in an abstract published at the ASCO 2021 meeting. Investigators drew their data from prescription information published by Wolters Kluwer (n = 130,836), sales data from IQVIA, and dosage information published by ION Solutions.

Investigators found that in 2020, 8.2% of new prescriptions for bevacizumab, rituximab, and trastuzumab were for biosimilar versions. For bevacizumab, there are currently 2 biosimilars available; rituximab, 3; and trastuzumab, 5.

Findings for use of trastuzumab biosimilars revealed a dramatic increase from the first year of availability to the next. In the first 3 months of 2019, 7.3% of initiating first-line patients were prescribed trastuzumab biosimilar vs reference product. In the first quarter of 2020, when all 5 trastuzumab biosimilars had become available, the new prescriptions rate was 80.5% for patients receiving first-line care.

Uptake rates differed for individual biosimilars. The investigators reported that Ruxience, the first available rituximab biosimilar, had initial uptake of just 2.3%.

And further, they did observe willingness among oncologists to switch patients from reference products to biosimilars. They said 11.1% of patients (bevacizumab, 11.3%; trastuzumab, 14.1%; rituximab, 7.9%) were transitioned from the reference biologics to biosimilars during treatment.

“Uptake was particularly rapid for trastuzumab biosimilars,” investigators said. “Among patients on trastuzumab at the time of its first biosimilar launch, 18.2% switched to [the Kanjinti trastuzumab biosimilar] in the first 90 days postlaunch.”

Significant savings were a feature of the use of biosimilars in the oncology practices, the authors said. Costs per biosimilar prescription were lower than the reference product prescription cost by 42.0%, 29.9%, and 89.5% for trastuzumab, rituximab, and bevacizumab, respectively.

“However, biosimilar launches had little impact on reference product pricing, with 2019 to 2020 year-over-year (YOY) differences in price per prescription close to the YOY averages in previous years (2015-2019) for all 3 reference products,” the authors wrote.

McGlynn KA, McGarry J, Patel KB, Clinton N. Real-world trends in biosimilar prescribing among oncology providers, 2019-2021. Presented at: ASCO 2021: June 3-7, 2021. Abstract e18701.

When biosimilars emerged in oncology, oncologists dipped in a toe and then got serious, according to a retrospective study on usage and savings presented at ASCO 2021.

Study Suggests Oncologists' Use of Biosimilars Grew From Trickle to Flood

An experiment with automatic prescribing of biosimilars at Texas Oncology resulted in a dramatic savings and increase in biosimilar vs originator usage rates, investigators reported at ASCO 2021.

Texas Oncology is a network of approximately 460 physicians and oncologists who serve patients with cancer in rural and urban communities throughout Texas. 

A central pharmacy team reviewed all prescriptions and substituted biosimilars for originator biologics, unless payers insisted otherwise or the relevant biosimilar was not in the practice formulary. Texas Oncology also compiled a weekly report identifying all patients who would benefit from switching to biosimilars, and substitutions were then made. In collaboration with McKesson Specialty Health, patient and clinician education was incorporated into the biosimilar usage effort to improve results.

Texas Oncology began the substitution in July 2020 with rituximab and followed up in September 2020 and October 2020 with bevacizumab and trastuzumab substitutions, respectively. By December 2020, utilization of biosimilars rose to 80% from 5% for rituximab, 88% from 9% for bevacizumab, and 74% from 8% for trastuzumab.

Investigators calculated the potential savings per administration at $550 for bevacizumab, $850 for trastuzumab, and $1400 for rituximab. “In 1 month alone, this project dramatically reduced cost by $4 million or 21% by conversion to these 3 biosimilars,” they wrote.

The investigators also predicted that additional savings would be possible by using multidose vials of biosimilar product rather than single-dose vials.

“Our comprehensive team approach successfully deploys therapeutic interchange of biosimilars for brand drugs in a community oncology practice which leads to substantial cost savings. This has real implications in controlling the total cost of care,” the authors of the study wrote.

Wilfong L, Dave N, Garey JS, et al. A successful model of biosimilar adoption in a community oncology practice. Presented at: ASCO 2021: June 3-7, 2021. Abstract 6514.

The substitution program was carried out in 2020 and yielded savings of $4 million in 1 month, investigators reported at ASCO 2021. 

Texas Oncology Reports Savings From Biosimilar Substitution Effort

Clinicians should expect 1 out of 7 patients with rheumatic disease to reverse switch from biosimilar etanercept (BS-ETA) to the originator brand (OR-ETA), investigators concluded in a Netherlands study presented at EULAR 2021.

Authors of the study sought to evaluate the incidence of reverse switching among patients (N = 342) who were switched to BS-ETA from OR-ETA. They noted the findings are relevant because reverse switching reduces the savings achieved by switching patients to BS-ETA.

Prior, open label studies reported that from 2.7% to 7.4% of patients retransitioned to originator etanercept after switching to the biosimilar, the authors noted.

In their study, 9.4% of patients reverse switched to the originator by the 1-year mark following initiation on BS-ETA, whereas 69.7% persisted on the biosimilar agent. By the end of the follow-up period, 4.4 years from baseline, 47 patients or 13.7% had retransitioned to OR-ETA. The median time before reverse switching was slightly less than 6 months.

Expressed in odds ratios (OR), where a value greater than 1 indicates higher odds of an association, the univariate determinants for reverse switching were identified as initiating corticosteroids or intensifying immunomodulatory treatments (OR 2.37; 95% CI, 1.03-5.45) and the number of rheumatology department visits (OR 2.0; 95% C, 1.55-2.74).

In multivariate analysis, only rheumatology department visits remained significantly associated with reverse switching (OR 2.19; 95% CI, 1.60-3.01).

Investigators concluded not only that roughly 14% of patients would switch back to OR-ETA but also patients who visit the rheumatology department more often were at higher risk for retransitioning.

They did not identify the brand or brands of etanercept biosimilar included in the study. The originator is Enbrel, an Amgen product.

Meijboom RW, Gardarsdottir H, Becker ML, ten Wolde S, Egberts ACG, Giezen TJ. Incidence and determinants associated with retransitioning from etanercept biosimilar to etanercept originator. Presented at EULAR 2021: June 2-5, 2021. Poster 0637.

EULAR

Investigators in the Netherlands observed that 13.7% of patients with rheumatic disease had switched back to etanercept originator at 4.4 years from baseline.

Etanercept Reverse Switching Is Measured in Netherlands Study

Investigators have reported a rare incidence of immunogenicity “with possible clinical and biological consequences” for patients treated with biosimilar rituximab (Riximyo, GP2013).

Investigators at the Rheumatology Department of Cochin Hospital, Paris, France, enrolled 159 patients who were treated with GP2013 (Riximyo; Sandoz) since March 2018 and included those who were previously treated with originator rituximab (RTX). The biosimilar is marketed in Canada and the European Union, but not in the United States. 

The immunogenicity of patients treated with rituximab is a rare event with possible clinical and biological consequences, especially in patients with high antibody levels.

Patients had rheumatoid arthritis (RA; n = 108), systemic sclerosis (SSc; n = 16), mixed connective tissue disease (MCTD; n = 15), and various other conditions in smaller proportions. The investigators said 25% of patients overall were RTX naive, and 75% were in maintenance therapy with RTX prior to switching to the biosimilar in March 2018.

Patients were tested for antidrug antibodies (ADAs) and residual rituximab concentrations. In the initial analysis, prior to the second GP2013 infusion, findings showed 8 patients (5%) positive for antidrug antibodies (RA, 5; MCTD, 1; SSc, 1; systemic lupus erythematosus [SLE], 1).

ADA rates were from 6 to greater than 100 ng/mL and “were associated with undetectable residual rituximab concentrations.” Among the 8 patients positive for ADAs, 6 had previously received RTX and 2 were RTX naive.

Investigators reported a trend toward higher mean (SD) body mass index for patients testing positive for ADAs (28 [7] vs 25 [6] kg/m

 = .12). They reported no associations between RTX immunization and age, disease duration, combination with conventional disease-modifying antirheumatic drugs, mean interval between infusions, or cumulative originator rituximab dose.

In stratification, the investigators reported 3 patients with high ADA levels (≥100 ng/mL), including 2 with RA and 1 with MCTD; decreased efficacy for 2 patients; incomplete B-cell depletion; RTX dose escalation from 500 mg to 1 g; and 1 severe allergic reaction.

Among 5 patients with mild ADA levels (6-22 ng/mL), the investigators reported 3 with RA, 1 with SLE, and 1 with SSc. Treatment was continued in all 5 cases with no loss of efficacy within an average of 13 months of follow-up. One minor allergic reaction was reported.

“The immunogenicity of patients treated with rituximab is a rare event with possible clinical and biological consequences, especially in patients with high antibody levels,” the investigators concluded.

Avouac J, Cougnaud Murail R, Goulvestre C, et al. Immunogenicity of rituximab biosimilar GP2013: a rare event, but not without consequences… Presented at: EULAR 2021; June 2-5, 2021. Poster 0600.

Immunogenicity was rare but concerning for patients who switched from originator rituximab to the biosimilar Riximyo, investigators reported. 

French Investigators Report Rituximab Immunogenicity Findings

Real-world findings for 2 Samsung Bioepis biosimilars were presented at EULAR 2021 and offered support for clinicians' use of these products in place of originator agents.  

A real-world analysis has demonstrated that patients with ankylosing spondylitis (axSpA) or rheumatoid arthritis (RA) can be initiated on the infliximab biosimilar SB2 (Flixabi) and patients with axSpA, RA, or psoriatic arthritis (PsA) can be switched to SB2 from the reference product without loss of disease control or dose penalty over the 12-month, post-initiation or transition period.

“Over 56% of SB2-naïve patients and over 79% of patients transitioned from the reference product remained on SB2 at 12 months following initiation,” investigators reported at EULAR 2021. The results were from the PERFUSE study, an ongoing, noninterventional study of patients with rheumatology (n = 496) and gastroenterology (n = 737) conditions receiving infliximab as routine therapy.

PERFUSE was initiated to provide understanding of long-term outcomes in patients who were started on SB2 in the real-world setting. Dosage, disease activity, and persistence on SB2 over time and up to 24 months after initiation were end points.

Investigators aim to continue the study to 24 months post initiation of SB2.

A real-world study of patients with autoimmune diseases demonstrated equivalence between adalimumab reference product and the biosimilar SB5 (Hadlima).

Investigators enrolled patients with RA, axSpA, PsA, ulcerative colitis, and Crohn disease who were initiated on SB5 following a minimum 16 weeks of treatment with the originator product (Humira). The study was conducted at clinics in Belgium, Germany, Ireland, Italy, Spain, and the United Kingdom.

Investigators sourced retrospective clinical data on patients (N = 504) for the 24 weeks prior to transition to SB5 and prospective or retrospective data for the 48 weeks following transition. Primary outcomes were baseline clinical characteristics, disease activity, and clinical management over time.

Authors of the study said for most patients there was no meaningful difference in disease score or dose regimen of SB5 by week 48 after transition to the biosimilar. Follow-up will continue until the fourth quarter of 2021.

“This investigative analysis provides a first insight into clinical management of patients over 48 weeks, in a contemporary cohort of European Union patients with established RA, axSpA, and PsA, switched from reference product to SB5 in clinical practice,” they wrote.

1. Fautrel B, Bouhnik Y, Dougados M, Freudensprung U, Addison J. PERFUSE: a French prospective/retrospective noninterventional cohort study of infliximab-naïve and transitioned patients receiving infliximab biosimilar SB2; 12-month analysis. Presented at: EULAR 2021; June 2-5, 2021. Poster 0614.

2. Müller-Ladner U, Gaffney K, Jadon D, Freudensprung U, Addison J. The PROPER study: interim analysis of a pan-EU real world study of SB5 biosimilar following transition from reference adalimumab in patients with rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis. Presented at: EULAR 2021; June 2-5, 2021. Abstract 0204.

Real-world clinical data compiled for patients with autoimmune disorders were presented at EULAR 2021.

Poster Roundup: Results Presented for Samsung Bioepis Biosimilars for Adalimumab, Infliximab

With its sights set on launching a high-concentration, citrate-free formulation of adalimumab in the European Union this year, Celltrion Healthcare presented positive 1-year results confirming equivalence of the biosimilar (CT-P17, Yuflyma) in patients with rheumatoid arthritis (RA) at EULAR 2021.

Celltrion hopes to gain a share of the lucrative market for high-concentration, citrate-free adalimumab (Humira; AbbVie), which has been displacing sales of lower-concentration adalimumab since 

. The Incheon, Republic of Korea, company would be the first to launch a biosimilar formulation of the high-concentration 100-mg/mL adalimumab product.

“We anticipate launching Yuflyma in 7 European countries, including Germany and France, in the third quarter of 2021 and in 3 additional European countries, including Italy, in the fourth quarter,” Celltrion told The Center for Biosimilars

No date for a US launch has been established so far; however, access to the US market is tightly controlled by the originator company’s extensive patent portfolio on adalimumab, and lower-concentration formulations are not expected to debut in the United States until 2023.

The randomized, double-blind, phase 3 trial for Yuflyma presented at EULAR, the annual European Congress of Rheumatology, met primary and secondary end points for efficacy, pharmacokinetics, safety, and immunogenicity, demonstrating outcomes comparable to reference adalimumab in patients (N = 648) with moderate to severe RA despite methotrexate treatment.

Patients were randomized 1:1 to receive a 40-mg dose of the biosimilar or reference adalimumab every 2 weeks through week 24. At week 26, patients were randomized again to treatment maintenance on the biosimilar (n = 303) or reference product (n = 153), or a switch from reference adalimumab to Yuflyma (n = 151). This round of treatment continued through week 48.

Demonstration of equivalent efficacy and comparable safety of CT-P17 to EU-sourced adalimumab in this study supports the ongoing clinical evaluation of CT-P17 as an adalimumab biosimilar.

For patients receiving maintenance therapy and those switched from reference adalimumab to Yuflyma up to week 52, the investigators reported comparable efficacy in terms of American College of Rheumatology–defined response rates for reduction in joint swelling and tenderness.

Similarly, drug concentrations at the lowest point prior to redosing (C

) also were comparable in all 3 treatment groups. Observed mean C

 levels fell within parameters reported for reference adalimumab (5-8 mcg/mL).

Safety profiles for patients receiving Yuflyma also were comparable. The most common treatment-emergent adverse event (TEAE) was neutropenia. Injection site reactions, hypersensitivity/allergic reactions, and infections also were similar to established TEAEs for reference adalimumab.

The investigators said antidrug antibody (ADA) and neutralising antibody (NAb) results also were equivalent among patient cohorts. ADA/Nabs were 28.4%/24.8%, 27.0%/24.3%, and 28.3%/26.3% in patients maintained on Yuflyma or reference adalimumab or switched to Yuflyma, respectively.

“Demonstration of equivalent efficacy and comparable safety of CT-P17 to EU-sourced adalimumab in this study supports the ongoing clinical evaluation of CT-P17 as an adalimumab biosimilar,” said Jonathan Kay, MD, a professor at the University of Massachusetts Medical School and the trial's principal investigator. 

In tandem with the trial results presentation, Celltrion stated that the European Commission has granted marketing authorization for the company’s infliximab biosimilar (Remsima) for use without intravenous (IV) infusion for new and existing patients with RA. Remsima received a positive recommendation for approval from the European Medicines Agency (EMA) as subcutaneous therapy without IV loading in adults with RA in March 2021.

Alvotech, a Reykjavik, Iceland–based company, also has developed a 100-mg/mL low-volume formulation of adalimumab (AVT02) but is facing legal action from AbbVie, which has made patent infringement 

 on its AVT02 marketing applications in September 2021 and late 2021, respectively. Alvotech has responded to the AbbVie litigation with a 

 seeking to invalidate Humira patents the company says are unjustified.

Celltrion announces the launch timing for its much anticipated high-concentration formulation of adalimumab and presents trial data supporting equivalence to the reference product.

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