Originator Etanercept Research Articles

Response to ‘‘To switch or not to switch’: the missing piece in the puzzle of biosimilar literature?’ by Scherlinger et al

Thank you for the interest1 in our recent publication, in which we explored treatment outcomes following a Danish mandatory switch from originator to biosimilar etanercept (SB4, 50 mg) in routine...

PMS70 - BIOSIMILAR AND ORIGINATOR ETANERCEPT: INFLUENCE OF LOCAL POLICY MEASURES AND PRACTICES ON MARKET DYNAMICS BETWEEN SWEDISH COUNTIES

This study aims to analyse market dynamics of originator and biosimilar etanercept in the different counties of Sweden, and examines the influence of local policy measures and practices, in addition to national policy. This study was performed in three steps: (1) a structured review of the literature on (biosimilar) policies in Sweden, (2) analysis of market data on the counties’ originator and biosimilar etanercept uptake (Q2 2012 to Q4 2017) provided by IQVIA, and (3) discussion of findings with a national health authority, key experts in Skåne, Västra Götaland, and Stockholm, and an industry representative. Notwithstanding the existence of a national managed entry agreement for etanercept, wide variations in biosimilar market shares between counties were observed (40% to 82% in 2017). Over time, early and late adopters of biosimilar etanercept can be distinguished. As prescriptions are often provided for a year, two possible approaches to switching patients were observed in counties: active pullback of prescriptions resulting in additional workload, or wait until the patient’s next visit. It can be noticed that switching is generally more driven by hospitals or individual physicians than by the county councils. Except for price differences between originator and biosimilar, the following factors that influence market dynamics differ between counties: presence of KOLs, local guidelines, and gainsharing arrangements. Regional variations in use of biosimilar etanercept can be seen although prices are coordinated nationally. The decision to switch or wait for lower prices is only affected by the county’s policy and attitudes of stakeholders towards biosimilars and switching. It seems that, for etanercept, counties are hesitant to switch patients, as it is associated with an increased administrative workload. Furthermore, a substantial price difference and guarantees that this will not change for a longer period are lacking in the etanercept market.

Cost evolution of biological agents for the treatment of spondyloarthritis in a tertiary hospital: influential factors in price.

Background Spending on biological agents has risen dramatically due to the high cost of the drugs and the increased prevalence of spondyloarthritis. Objective To evaluate the annual cost per patient and cost for each biological drug for treating patients with spondyloarthritis from 2009 to 2016, and to calculate factors that affect treatment cost, such as optimizing therapies by monitoring drug serum levels, the use of biosimilar-TNF inhibitors, and official discounts or negotiated rebates in biologicals acquired by the pharmacy department. Method Retrospective, observational study in a Spanish tertiary hospital. Main outcome Annual cost per patient and per drug. Factors that influenced the costs and socio-demographic parameters and disease activity. Results A total of 129, 215, and 224 patients were treated in 2009, 2013, and 2016, respectively. The annual cost per patient decreased: EUR11,604 in 2009, EUR8513 in 2013, and EUR7464 in 2016. The introduction of new drugs drives economic competition, leading to total savings per drug, with discounts reaching 5.8, 12.4, 16.7, 17.7, 13.7, and 24.8% for original infliximab, etanercept, adalimumab, ertolizumab, golimumab, and secukinumab, respectively, while rebates for biosimilar infliximab reached 31.90% in 2016. The number of patients with optimized therapies reached 47.5% in 2016, which led to cost savings of EUR798,614, in addition to savings from official discounts and rebates of EUR252,706 and savings from optimized therapies of EUR545,908 in 2016. Conclusion The cost of biological treatments declined after official discounts, negotiated rebates, and optimized therapies, leading to a significant decrease in the annual cost per patient. The greatest contribution to economic savings in biological therapy according to our study was biological therapy optimization.

Acceptance rate and sociological factors involved in the switch from originator to biosimilar etanercept (SB4)

ObjectiveTo study acceptance rate and factors influencing acceptance of the switch from originator etanercept (Enbrel©) to biosimilar etanercept (SB4, Bénépali©) in patients with rheumatic disease. MethodsPatients with a well-controlled rheumatic disease consulting in our rheumatology department were offered the switch for SB4. After oral and written information concerning biosimilar, free choice to accept the switch was left to the patients. The main outcome was primary switch acceptance rate defined by switch acceptance during the initial consult. Real switch adherence, socio-cultural factors and beliefs influencing switch acceptance rate were retrieved during a telephonic interview at distance from the consultation. ResultsFifty-two patients were eligible for the switch: 32 (62%) with spondyloarthritis and 20 (38%) with rheumatoid arthritis. The primary acceptance rate was 92% (48/52). Patients refusing the switch were more likely to report a bad opinion on generic drugs (100% vs 11%, p < 0.001). Other patient characteristics were roughly identical except for a statistical trend in the refusal group toward older age (61.4vs 50.7years, p = 0.08) and longer disease duration (26vs 12.1years, p = 0.05). Despite initial acceptance, two patients did not begin SB4 after receiving negative information by their regular pharmacist. Real SB4 switch rate was 85% (44/52) and 86% (38/44) of patients reported a good experience of the switch. ConclusionsAcceptance rate of the switch from originator to biosimilar etanercept is high. Patient information, physician and pharmacist knowledge on biosimilars should be taken into account in order to improve their diffusion.

E55 Analysis of rheumatoid arthritis patients who failed the switch from originator etanercept to biosimilar etanercept in Croydon

e55 Analysis of rheumatoid arthritis patients who failed the switch from originator etanercept to biosimilar etanercept in Croydon

Physicochemical Characterization, Glycosylation Pattern and Biosimilarity Assessment of the Fusion Protein Etanercept.

Etanercept is a soluble fusion protein of the tumor necrosis factor receptor (TNFR) extracellular domain, linked to an Fc part of IgG1. It possesses three N- and 13 O-glycosylation sites. Due to its complex structure, an analytical challenge is facing the development and approval of biosimilars. In the current study, physicochemical characterization using state-of-the-art analytics was performed to analyze intact and subunit masses, post-translational modifications (PTMs), higher order structure and potency of Etanercept originator Enbrel® and its biosimilar Altebrel™ (AryoGen Pharmed) in accordance to critical quality attributes of biopharmaceuticals. Intact mass and subunit analysis revealed a size of about 126kDa for both biologicals. Similar glycoprotein species for the complete monomer and the Fc domain of originator and follow-on product were observed, however, small differences in lysine variants and oxidation were found. N-Glycopeptide analysis with UHPLC-QTOF-MSE confirmed the N-glycosylation sites (N149, N171 and N317) as well as Fc-specific glycosylation on N317, and TNFR-specific highly sialylated glycans on N149 and N171 on both investigated products. Small quantitative variations in the N-glycan profile were detected, although the N-glycans were qualitatively similar. Four different O-glycopeptides bearing core 1-type glycans were detected. For both, N- and O-glycopeptide analysis, determination was achieved without prior cleavage of the sialic acid residues for the first time. In addition, ion mobility spectrometry data confirmed close similarity of higher-order structure of both biologics. Furthermore, a neutralization assay, investigating the impact of altered PTMs on potency, indicated that the differences within all batches are still in the acceptable range for biosimilarity.

Characterization and non-clinical assessment of the proposed etanercept biosimilar GP2015 with originator etanercept (Enbrel®)

ABSTRACTBackground and objective: Biosimilars are approved biologics that are comparable to an originator product with respect to quality, safety and efficacy. Herein, the authors describe the functional and non-clinical studies designed to determine the biosimilarity of GP2015 and originator etanercept (Enbrel®).Methods: The development of an Enbrel biosimilar (GP2015) involved extensive characterization of the originator. A step-wise target-directed and iterative technical development program involving state-of-the-art functional characterization studies and non-clinical evaluations (pharmacokinetics, pharmacodynamics and safety/toxicology) was applied with the aim of confirming that GP2015 is comparable to originator (Enbrel) at the non-clinical level.Results: In in vitro tests, GP2015 and Enbrel had comparable binding affinities to TNF-α, C1q complement and a complete panel of Fc-Receptors. Comprehensive functional characterization testing confirmed the comparability of GP2015 with Enbrel in terms of its ability to bind to and neutralize TNF-α, which reflects the primary mechanism of action of etanercept. Non-clinical data confirmed that the proposed biosimilar to Enbrel, GP2015, is comparable with regards to its pharmacokinetic properties and pharmacodynamic activity, and efficacy as well as safety/toxicity.Conclusion: The proposed Enbrel biosimilar, GP2015, was shown to be comparable to its originator product in studies designed to confirm biosimilarity.

Will Biosimilars Change the Treatment Paradigm in Psoriasis?

Prof Augustin opened the meeting and reviewed the use of systemic treatments recommended for moderate-to-severe psoriasis. Data indicating a lack of access to biologic treatments were presented, and barriers to the use of biologics, including both patient and physician-related cost, were discussed. The opportunity for improved access to biologic treatment options, portrayed by the availability of biosimilars, and the potential to improve healthcare for patients with psoriasis was presented. Dr Schiestl explained that the demonstration of biosimilarity for regulatory requirements is based on the totality of evidence generated from analytical, non-clinical, and clinical data. The physicochemical and biological assessments performed for comparison of the proposed biosimilar and the originator molecule, using state-of-the-art technology, are most sensitive. Comparative, analytical, and functional testing therefore represent the major part of the comparability exercise, proving that the biosimilar and originator product contain essentially the same active substance. After demonstration of similarity at an analytical and functional level, suitable comparative pharmacodynamics (PDs) and/or pharmacokinetics (PKs) and/or safety studies in animal models are performed. Comparative clinical PKs/PDs and safety is assessed in healthy volunteers as an essential part of the clinical development programme. A final confirmatory Phase III clinical study is conducted in a sensitive patient population to confirm similar safety and efficacy of the biosimilar compared to the originator molecule. Dr Gerdes explained why psoriasis is a sensitive and robust indication for confirming clinical efficacy of a biosimilar. He presented data from the EGALITY confirmatory study of the etanercept biosimilar (GP2015) in patients with moderate-to-severe psoriasis to compare safety and efficacy, and provided data on multiple switches between the originator etanercept (ETN) and the biosimilar. The trial confirmed the clinical equivalence of the efficacy and safety of GP2015 with ETN; no new safety signals were observed. Switching between the originator and biosimilar had no effect on safety or efficacy over the 52-week study.

Patient-reported Outcomes in a Randomized Trial of Etanercept in Psoriatic Arthritis

To evaluate the effects of etanercept treatment on patient-reported outcomes (PRO) in patients with psoriatic arthritis (PsA). A 24-week double-blind comparison to placebo was followed by a 48-week open-label phase in which all eligible patients received etanercept. PRO were measured using the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI), the Medical Outcomes Study Short-Form (SF-36), the EQ-5D visual analog scale (VAS), and the American College of Rheumatology (ACR) patient pain assessment. Beginning at Week 4 and continuing through Week 24 of double-blind treatment, patients treated with etanercept had significantly higher mean percentage improvement in HAQ-DI relative to baseline than patients given placebo (53.6% vs 6.4% at Week 24; p < 0.001). After 48 weeks of open-label treatment with etanercept, the mean percentage change from study baseline was 52.8% for the original etanercept group and 46.9% for the original placebo group, with 41.2% of patients overall achieving a HAQ-DI of 0. Mean changes relative to baseline for SF-36 physical component summary scores, EQ-5D VAS, and ACR pain assessment were also significant in the double-blind period for etanercept compared with placebo (p < 0.001 for all 3 measures). Patients taking placebo achieved similar improvements once they began treatment with etanercept in the open-label period. Patients with PsA treated with etanercept reported significant improvements in physical function that were almost 10 times the improvement seen with placebo and were maintained for up to 2 years. Almost half of patients treated with etanercept reported no disability by the end of the study.

Long-term Safety and Efficacy of 50 mg of Etanercept Twice Weekly in Patients With Psoriasis

To evaluate the safety and efficacy of long-term treatment of psoriasis with etanercept, 50 mg twice weekly. A phase 3, randomized, double-blind trial with an open-label extension. A total of 618 adult patients with moderate to severe plaque psoriasis were studied at 39 medical centers in the United States and Canada from May 23, 2003, through June 22, 2005. Patients were randomized to receive placebo or etanercept for 12 weeks. Beginning with week 13, all patients (N=591) received etanercept. Exposure-adjusted adverse event rates were calculated. Efficacy measures included efficacy and patient global assessment of psoriasis. Exposure-adjusted rates of adverse events, serious adverse events, infections, and serious infections were similar for placebo and etanercept treatments. Nonneutralizing antibodies to etanercept, observed in 18.3% of patients, had no apparent effect on safety or efficacy. Patients responded within 2 weeks to etanercept, with statistically significant differences in the Psoriasis Area and Severity Index and Dermatology Life Quality Index between the etanercept and placebo groups at week 12. At week 24, after 12 weeks of open-label etanercept treatment, patients in the original placebo group had clinical benefits comparable to those of patients in the original etanercept group. As both groups progressed through the open-label period, the Psoriasis Area and Severity Index response peaked at week 48. At week 96, 51.6% of the original placebo-treated patients and 51.1% of the original etanercept-treated patients had improvements from baseline in the Psoriasis Area and Severity Index of at least 75%. Extended exposure to 50 mg of etanercept twice weekly resulted in exposure-adjusted rates of adverse events and infections similar to those in patients receiving placebo. Improvements in physician- and patient-reported measures of psoriasis severity were observed for up to 96 weeks of continuous etanercept therapy. Trial Registration clinicaltrials.gov Identifier NCT00111449.