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Global support and standardization of regulation for biosimilars approval owes much of its legacy to the World Health Organization (WHO), since the first guidance by the organization on the matter was released in 2009. Since then, and with over a decade of research, the 2022 revision provides opportunities for time and financial savings to pharmaceutical manufacturers aiming to prove similarity of a potential biosimilar product to some reference product, particularly by clarifying that the use of a non-local reference product as a comparator in certain studies is permissible. This declaration has important implications, particularly in the emerging biological markets of the Middle East and North Africa region, where WHO guidelines have been integral to the regulatory framework of over a dozen countries for more than a decade. This article aims to review the impact of this revision on these countries and relevant policies on non-local comparator usage. Since 2022, this revision has been adopted only in Egypt. Many North African countries are yet to adopt a first draft of the formalized guidance. This analysis revealed that, although many of these countries reference the WHO guidelines, hesitation remains in terms of sourcing comparator products outside the US or European countries. This likely translates to slow regional development and cooperation of functioning, sustainable biosimilars markets. Future studies will be necessary to evaluate the continued development of guidance within these countries and changes in comparator sourcing norms as more time is allowed for their policies to mature and adapt to new standards.

Aims Methods Results Conclusions Biosimilar products have clinical characteristics similar to those of brand‐name products and can reduce medical costs. However, the use of biosimilar products for osteoporosis treatments remains limited due to concerns regarding its safety and efficacy. We aimed to clarify the effectiveness and safety of the biosimilar teriparatide compared with those of the reference product using the incidence of new fractures and osteosarcoma as outcomes in osteoporosis patients.This study used the DeSC database, which contains medical claims data for various insurers in Japan. We included patients with osteoporosis aged ≥65 years who newly received either biosimilar teriparatide or the reference products between April 2019 and November 2022. Competing risk analyses were performed with adjustments for patient characteristics. The primary and secondary outcomes were the occurrence of new fractures and osteosarcoma, respectively.Among 45 861 included patients, 3613 and 42 248 were in the biosimilar and reference product groups, respectively. The median follow‐up duration was 439 days. New fractures occurred in 6.7% of patients. Cumulative incidence function curves showed similar risks of new fractures over time in both groups. The cause‐specific hazard ratio for new fractures was 0.95 (95% confidence interval: 0.82–1.11) for the biosimilar group compared with that of the reference product group. The incidence of osteosarcoma did not differ significantly between the groups (P = .559).The biosimilar teriparatide showed effectiveness and safety comparable with those of the reference products in treating osteoporosis patients. Our results suggest that clinicians need not hesitate to prescribe biosimilar teriparatide for osteoporosis patients. [ABSTRACT FROM AUTHOR]

Glycan profile comparisons are one of the most tedious analytical exercises for establishing compliance with recombinant therapeutic protein batches. Based on its intensive research, the FDA has confirmed that lectin array binding with fluorescent monitoring is the fastest and most reliable method for profile comparisons. Using a database of over 150 biological products expressed in nine diverse mammalian cell systems, the FDA immobilized 74 lectins to study their binding using fluorescently labeled glycoproteins. The FDA identified nine distinct lectins from a custom-designed lectin microarray: rPhoSL, rOTH3, RCA120, rMan2, MAL_I, rPSL1a, PHAE, rMOA, and PHALs, which detect core fucose, terminal GlcNAc, terminal β-galactose, high mannose, α-2,3-linked sialic acids, α-2,6-linked sialic acids, bisecting GlcNAc, terminal α-galactose, and triantennary structures, respectively. This method can be used for screening and routine testing and to monitor batch-to-batch variability of therapeutic proteins, including establishing analytical similarity as a crucial part of biosimilar development. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluated the pharmacokinetic (PK) equivalence between BP02 (a proposed trastuzumab biosimilar) and the reference trastuzumab approved in the EU (EU-trastuzumab) and the US (US-trastuzumab). Methods: In this phase 1, double-blind, parallel-group trial, 111 healthy male volunteers were randomized 1:1:1 to receive a single 6-mg/kg intravenous infusion of BP02, EU-trastuzumab, or US-trastuzumab and were evaluated for 78 days. Serum drug concentration–time data were analyzed by non-compartmental methods. The PK similarity of BP02 to the two reference products, and between EU-trastuzumab and US-trastuzumab, was determined using the standard 80–125% bioequivalence criteria. Results: Baseline demographics for the 111 subjects with evaluable pharmacokinetics were similar across all treatment groups. PK profiles were similar for the three products. The 90% confidence intervals (CIs) for the ratios of area under the serum concentration–time curve (AUC) from the time of dosing to infinity (AUC0-inf), AUC from the time of dosing until the time of the last quantifiable concentration (AUC0-t), and peak serum concentration of trastuzumab (Cmax) were within 80% to 125% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms, with treatment-related AEs reported by 73.0%, 73.0%, and 89.2% of the subjects in the BP02, EU-trastuzumab, and US-trastuzumab groups, respectively. The most common AEs were headache, infusion-related reactions, and upper-respiratory-tract infections. Four subjects—three in the US-trastuzumab group and one in the BP02 group—discontinued the study due to AEs. All post-dose samples except for two tested negative for anti-drug antibodies. Conclusion: This study demonstrates the PK similarity among BP02, EU-trastuzumab, and US-trastuzumab. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab. Trial Registration: ANZCTR number: ACTRN12621000573853. [ABSTRACT FROM AUTHOR]

Introduction: Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. Methods: We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. Results: Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9 years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7 months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9–98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. Conclusion: Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. ClinicalTrials.gov Registration: NCT03892655. [ABSTRACT FROM AUTHOR]

Introduction: RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical, and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. Methods: In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01–11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. Results: The median follow-up period was 77.0 months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5 months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. Conclusion: This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. Trial Registration: ClinicalTrials.gov Identifier: NCT04928573. June 16, 2021, "retrospectively registered". [ABSTRACT FROM AUTHOR]

Background: Healthcare sustainability is a global challenge. Various value-driven healthcare strategies have been implemented by Singapore's national health technology assessment (HTA) agency, the Agency for Care Effectiveness (ACE). Considering the high and growing expenditure on biologics, strategies have been implemented to drive the use of biosimilars. As Singapore has reached the 5-year mark since the subsidy listing of the first monoclonal antibody biosimilar infliximab, this review aimed to evaluate the impact of these strategies on the changes in adoption rates, utilisation, spending and cost savings for biosimilars in the public healthcare sector. Methods: A retrospective cross-sectional study was conducted using aggregated drug utilisation data from all public healthcare institutions. Five monoclonal antibodies with biosimilars, namely infliximab, adalimumab, trastuzumab, rituximab and bevacizumab, were included in this study. The outcomes evaluated were the monthly trends for utilisation volume, proportion attributed to biosimilar use, and drug spending up to December 2022. The simulated cost savings associated with biosimilar adoption were also reported. Results: After subsidy implementation, an upward trend in biosimilar use and proportion attributed to biosimilar adoption was observed, while spending reduced substantially. The adoption rate of most biosimilars reached more than 95% within 1 year of listing. Drugs with more than one approved biosimilar brand at the time of subsidy listing reported substantial price reductions of over 80%. Overall, spending for the five monoclonal antibodies have significantly reduced after biosimilar subsidy listing, with an estimated cumulative cost savings of $136 million over 5 years. Conclusion: Value-driven healthcare strategies implemented in Singapore's public healthcare institutions have contributed to high adoption rates of biosimilars and have improved affordable access through lower treatment costs. This in turn has led to significant cost savings to the healthcare system. [ABSTRACT FROM AUTHOR]

The introduction of anti-tumor necrosis factor α (TNFα) biologics significantly innovated inflammatory bowel disease (IBD) treatment and increased medical costs. The recent expiration of patents of some anti-TNFα biologics (such as infliximab and adalimumab) facilitated the development of biosimilars. Comparable pharmacokinetic, efficacy, safety, and immunogenicity profiles between anti-TNFα originators and biosimilars were demonstrated in different studies. Anti-TNFα biosimilars hold promise for reducing the high cost of biologics and increasing patient access to biologics. In this review, we outline the current data on the use of anti-TNFα originators and biosimilars in patients with IBD, with a focus on the efficacy, safety, and immunogenicity profiles of infliximab and adalimumab biosimilars. The potential benefits, challenges, and future directions of anti-TNFα biosimilars are also discussed in the review. [ABSTRACT FROM AUTHOR]

Pharmacopeia monographs are not intended to establish biosimilarity. However, the US Food and Drug Administration (FDA) has stopped the US Pharmacopeia (USP) from creating monographs for biological drugs due to the need for side-by-side comparisons with the reference products. The USP can create Biological Product Specifications (BPS), not to be labeled as monographs, based on the analytical testing of reference products and validated test methods that will remove the need for side-by-side analytical testing of biosimilars with reference products. Scientific arguments confirm that this plan is logical and capable of creating global quality standards for biosimilars to allow their interchangeability with other biosimilars. While the regulatory agencies have waived many high-cost biosimilar tests, analytical assessment is the most sensitive test; reducing its cost will further enhance the entry of biosimilars with no clinically meaningful difference. [ABSTRACT FROM AUTHOR]

Structured product quality data offer tremendous promise to revolutionize the submission of drug applications. However, the quality attributes for biological products do not have a systematic naming taxonomy, and consequently this limit poses a critical challenge in the development of systems for structured regulatory submissions. Here, we describe the creation of a controlled vocabulary with a structured taxonomical naming approach for quality attributes of therapeutic proteins. Additionally, we endeavor to make the case for why such systematic harmonized naming is required to support the successful implementation of structured data systems. We also describe the key principles of our structured naming approach, including a top-down view of the product and protein structure and a distinction between a quality attribute and the test to evaluate the attribute. Finally, we describe how this approach can accommodate emerging product types, advanced manufacturing technologies, and be used across the variety of submission sections in a regulatory dossier that discusses quality attributes. [ABSTRACT FROM AUTHOR]

Introduction: SB15 is a proposed biosimilar product of reference aflibercept (Eylea®), an approved biological drug product for retinal diseases including neovascular age-related macular degeneration (nAMD). This study aimed to assess the analytical similarity between SB15 and its commercially available reference product (RP) sourced from the United States (US-aflibercept) and European Union (EU-aflibercept) in terms of structural, physicochemical, and biological properties. Methods: A panel of state-of-the-art analytical methods was used for the comprehensive characterization of SB15 and US/EU-aflibercept. In terms of the structural and physicochemical properties, primary structure; post-translational modifications (PTM); higher-order structure; purity and impurities; charge variants; and glycosylation were compared. In addition, biological characterization including mechanism of action (MoA)-related and Fc-related biological activities was conducted. Results: Analytical similarity between SB15 and US/EU-aflibercept was demonstrated. The primary and higher-order structure of SB15 was confirmed to be comparable to that of US/EU-aflibercept. In addition, there were no meaningful differences in the physicochemical properties in terms of size and charge heterogeneity between SB15 and its RP. SB15 and RP were similar in biological activities including MoA-related binding activities, potencies, and Fc-related biological functions. Consequently, SB15 was confirmed to be highly similar to US/EU-aflibercept. Conclusions: Based on a comprehensive analytical similarity assessment of structural, physicochemical, and biological properties, SB15 was demonstrated to be highly similar to US/EU-aflibercept RP, supporting safe and effective use of SB15. [ABSTRACT FROM AUTHOR]

Introduction: SB15 is a proposed biosimilar product of reference aflibercept (Eylea®), an approved biological drug product for retinal diseases including neovascular age-related macular degeneration (nAMD). This study aimed to assess the analytical similarity between SB15 and its commercially available reference product (RP) sourced from the United States (US-aflibercept) and European Union (EU-aflibercept) in terms of structural, physicochemical, and biological properties. Methods: A panel of state-of-the-art analytical methods was used for the comprehensive characterization of SB15 and US/EU-aflibercept. In terms of the structural and physicochemical properties, primary structure; post-translational modifications (PTM); higher-order structure; purity and impurities; charge variants; and glycosylation were compared. In addition, biological characterization including mechanism of action (MoA)-related and Fc-related biological activities was conducted. Results: Analytical similarity between SB15 and US/EU-aflibercept was demonstrated. The primary and higher-order structure of SB15 was confirmed to be comparable to that of US/EU-aflibercept. In addition, there were no meaningful differences in the physicochemical properties in terms of size and charge heterogeneity between SB15 and its RP. SB15 and RP were similar in biological activities including MoA-related binding activities, potencies, and Fc-related biological functions. Consequently, SB15 was confirmed to be highly similar to US/EU-aflibercept. Conclusions: Based on a comprehensive analytical similarity assessment of structural, physicochemical, and biological properties, SB15 was demonstrated to be highly similar to US/EU-aflibercept RP, supporting safe and effective use of SB15. [ABSTRACT FROM AUTHOR]

This research is based on three fundamental aspects of successful biosimilar development in the challenging biopharmaceutical market. First, biosimilar regulations in eight selected countries: Japan, South Korea, the United States, Canada, Brazil, Argentina, Australia, and South Africa, represent the four continents. The regulatory aspects of the countries studied are analyzed, highlighting the challenges facing biosimilars, including their complex approval processes and the need for standardized regulatory guidelines. There is an inconsistency depending on whether the biosimilar is used in a developed or developing country. In the countries observed, biosimilars are considered excellent alternatives to patent-protected biological products for the treatment of chronic diseases. In the second aspect addressed, various analytical AI modeling methods (such as machine learning tools, reinforcement learning, supervised, unsupervised, and deep learning tools) were analyzed to observe patterns that lead to the prevalence of biosimilars used in cancer to model the behaviors of the most prominent active compounds with spectroscopy. Finally, an analysis of the use of active compounds of biosimilars used in cancer and approved by the FDA and EMA was proposed. [ABSTRACT FROM AUTHOR]

Simple Summary: The ADCC bioassays used to assess mAb-induced ADCC require continued development/refinement to meet regulatory requirements. We used trastuzumab and a lactate de-hydrogenase (LDH)-based ADCC bioassay as a model to define critical parameters of the ADCC bioassay. We find that a 4 to 24 h recovery cultivation is required to restore peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cell activity toward ADCC when using cryopreserved PBMCs. Several bioassay parameters, including preparation of effector cells, E/T ratio, target cell selection, bioassay media components, and treatment time can also influence the data quality of the ADCC activity. The mechanisms of mAb-induced ADCC have been well established. However, the ADCC bioassays used to quantify mAb-induced ADCC require continued development/refinement to properly assess and compare the potency of newly developed therapeutic mAbs and biosimilars to meet regulatory requirements. We used trastuzumab and a lactate dehydrogenase (LDH)-based ADCC bioassay as a model to define critical parameters of the ADCC bioassay, describing how several bioassay parameters, including preparation of effector cells, E/T ratio, target cell selection, bioassay media components, and treatment time can influence the data quality of the ADCC activity. We confirm that a 4 to 24 h recovery cultivation is required to restore peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cell activity toward ADCC when using cryopreserved PBMCs. Furthermore, we delineated the cellular mechanisms underlying the restored ADCC activity following the recovery cultivation. We observed that CD69, an early marker of NK cell activation, was upregulated and a new subset CD56dim/CD16dim population was dramatically increased in the recovered NK cells, which led to an increase in expression and secretion of perforin, granzyme B, and cytokine production. This study provides comprehensive technical insights into ADCC bioassay optimization to inform trastuzumab biosimilar development. The knowledge gained from this study can also be leveraged to guide bioassay development for therapeutic mAbs with ADCC as the primary mechanism of action. [ABSTRACT FROM AUTHOR]

Annual out-of-pocket expenditures for patients with inflammatory bowel disease (IBD) are estimated to be as high as $41,000, with medications, such as biologics, being one of the main cost contributors. Although biologics have revolutionized IBD management, these medications are costly owing to their molecular makeup and manufacturing processes. Biosimilars, which are biologic medications that are highly similar to the US Food and Drug Administration (FDA)-approved reference product with no clinically meaningful differences in safety, purity, or potency, offer the same therapeutic benefits at a reduced cost. Other additional benefits offered with biosimilars include increased treatment access and fostered development of new therapeutic options. Despite the expansion of biosimilars in IBD, their adoption and utilization have been suboptimal in the United States. This article provides an overview of the biosimilar landscape in IBD, including FDA-approved biosimilars available, and a clinical guide to navigate switching to biosimilars in various clinical scenarios based on current evidence. [ABSTRACT FROM AUTHOR]

To determine the formula for biomimetic warm-mix regeneration and fulfill the requirements of a "high waste asphalt mixture content, high quality, and high level" for its usage in reclaimed asphalt pavement (RAP), this paper first determined the suitable preparation process and formula for biomimetic warm-mix regeneration based on orthogonal experiments and a gray correlation analysis. Then, the optimum dosage of the warm-mix regenerant was determined by a uniaxial penetration test, low-temperature splitting test, and freeze–thaw penetration test. The rutting test was conducted to characterize the high-temperature performance of the asphalt mixture. The Immersion Marshall Test and the freeze–thaw splitting test were used to characterize the water stability of the recycled asphalt mixture. The low-temperature small beam test was employed to study the low-temperature performance of the recycled asphalt mixture. The asphalt's short-term and long-term aging processes were simulated using the rotary thin-film oven test (RTFOT) and the pressure aging test (PAV). The action mechanism of biomimetic warm-mix regeneration was revealed by Fourier-transform infrared spectroscopy (FTIR). Finally, a comprehensive thermal performance test was conducted on the aged asphalt after biomimetic warm-mix regeneration. The results showed that the self-made biomimetic warm-mix regeneration agent exhibited an excellent regenerative effect on RAP and significantly reduced the mixing temperature of the styrene–butadiene–styrene (SBS)-modified asphalt mixture. In addition, the self-made biomimetic warm-mix regeneration agent effectively improved the high- and low-temperature performance of the recycled asphalt mixture, but had no noticeable effect on the water stability. The suggested dosage of the biomimetic warm-mix regeneration agent was 6%, and the mixing temperature was 130 °C. The microscopic chemical analysis revealed that biomimetic warm-mix regeneration restored the performance of aged asphalt by supplementing the light component. The change rules of the chemical functional groups and the comprehensive thermal properties of the recycled mixture showed a good correlation with the change rules of its high- and low-temperature performance. [ABSTRACT FROM AUTHOR]

Abstract Objectives To analyse clinical outcomes of a non-medical switch from originator adalimumab (ADA) to its ABP501 biosimilar (ABP) over 6 months in patients with inflammatory rheumatic musculoskeletal diseases (RMD) in relation to comorbidity as a risk factor for therapy discontinuation. Methods RMD patients switching from originator ADA to ABP were identified from a large routine database from October 2018 onwards. Documented clinical data at the time of non-medical switching (baseline), and at 3 and 6 months were collected. Comorbidities were represented by the Charlson Comorbidity Index (CCI) at baseline and patients were categorized based on CCI > 0. Differences in the ABP retention rate over 6 months between patients with CCI = 0 and patients with CCI > 0 were analysed using Bayesian exponential regression. Results A total of 111 patients with axial spondyloarthritis (n = 68), rheumatoid arthritis (n = 23) and psoriatic arthritis (n = 15), were identified, 74.8% of whom had continued treatment with ABP after 6 months, while a smaller proportion had either switched to another ADA biosimilar (10.8%), switched back to originator ADA (7.2%), switched to a different biologic (3.6%), or dropped out (3.6%). At baseline, a CCI > 0 was found in 38% of patients. Cardiovascular comorbidities (40%) were most prevalent followed by diseases of the skin (33%), the gastrointestinal tract (20%) and the eye (20%). ABP treatment was continued after 6 months in 74% of patients with CCI = 0 and in 76% with CCI > 0. Bayesian analysis showed only a small difference (months) in the APB continuation rate between groups (estimate 0.0012, 95% credible interval (CrI) -0.0337 to 0.0361). Adjusting for age, sex, and disease subtype revealed somewhat shorter retention rates for patients with CCI > 0, but the distribution of the difference included 0 (estimate -0.0689, 95% CrI -0.2246 to 0.0234). Conclusion In a non-medical switch scenario of RMD patients, there was no evidence for a considerable difference in ABP retention rates over 6 months between comorbidity groups.

The incidence of blindness due to exudative retinal diseases reduced significantly over the twenty years of the use of anti-vascular endothelial growth factor (VEGF) therapy in ophthalmology. However, despite advances in recent years, current outcomes of anti-VEGF therapy for exudative retinal diseases are not always optimal. This review aims to highlight the advances in the development of VEGF inhibitors and identify potential ways of improving the outcomes of anti-VEGF therapy for, and solving current problems in the management of, exudative retinal diseases.

The field of rheumatic disease treatment has undergone a profound transformation, characterized by significant progress in research, precision medicine, and holistic patient care. Rheumatic diseases, a diverse group of conditions affecting the joints, muscles, bones, and connective tissues, have historically caused pain and disability for millions worldwide. Traditional treatment methods primarily centered on managing symptoms, relying heavily on medications like nonsteroidal anti-inflammatory drugs and corticosteroids. While these approaches provided some relief, they often carried side effects and had limited long-term effectiveness. However, recent years have witnessed remarkable breakthroughs in our understanding and management of rheumatic diseases. Pioneering research has unveiled the complex immunological mechanisms at the core of these disorders, leading to the development of targeted therapies that specifically inhibit key molecules and pathways responsible for inflammation. Biologic medications, such as tumor necrosis factor inhibitors and interleukin-6 inhibitors, have completely transformed treatment paradigms by not only alleviating symptoms but also potentially altering the course of diseases like rheumatoid arthritis (RA). Moreover, precision medicine has emerged as a central pillar of rheumatic disease management, creating personalized treatment strategies based on a patient’s unique genetic, molecular, and immunological profile. Genetic markers, such as the human leukocyte antigen gene, can identify individuals with a heightened risk of developing RA, allowing for proactive interventions that may prevent or mitigate the onset of the disease. Combination therapies, which combine different classes of medications, offer hope for patients who do not respond adequately to single-drug treatments. Beyond pharmaceutical interventions, holistic patient care encompasses lifestyle modifications, physical therapy, occupational therapy, and patient education, all aimed at improving overall well-being. Looking forward, ongoing research, innovation, and collaborative efforts among healthcare professionals, researchers, and patients are essential to sustain the trajectory of progress in rheumatic disease treatment. The future holds the potential for further breakthroughs, poised to reshape the lives and futures of individuals grappling with the complexities of these challenging health conditions, ushering in an era of renewed hope and an improved quality of life.

Abstract Background Biosimilars are biologic drugs that have the potential to increase the efficiency of healthcare spending and curb drug-related cost increases. However, their introduction into hospital formularies through initiatives such as non-medical switching must be carefully orchestrated so as not to cause treatment discontinuation or result in increased health resource utilization, such as additional visits or laboratory tests, among others. This retrospective cohort study aims to assess the impact of the introduction of CT-P13 on the healthcare expenditures of patients who were treated with originator infliximab or CT-P13. Methods Gastroenterology, immunoallergology and rheumatology patients treated between September 2017 and December 2020 at a university hospital in Western Switzerland were included and divided into seven cohorts, based on their treatment pathway (i.e., use and discontinuation of CT-P13 and/or originator infliximab). Costs in Swiss francs were obtained from the hospital's cost accounting department and length of stay was extracted from inpatient records. Comparisons of costs and length of stay between cohorts were calculated by bootstrapping. Results Sixty immunoallergology, 84 rheumatology and 114 gastroenterology patients were included. Inpatient and outpatient costs averaged (sd) CHF 1,611 (1,020) per hospital day and CHF 4,991 (6,931) per infusion, respectively. The mean (sd) length of stay was 20 (28) days. Although immunoallergology and rheumatology patients had higher average costs than gastroenterology patients, differences in costs and length of stay were not formally explained by treatment pathway. Differences in health resource utilization were marginal. Conclusions The introduction of CT-P13 and the disruption of patient treatment management were not associated with differences in average outpatient and inpatient costs and length of stay, in contrast to the results reported in the rest of the literature. Future research should focus on the cost-effectiveness of non-medical switching policies and the potential benefits for patients.

Objective: To evaluate the impact of the entry of biosimilars on the pricing of eight biologic products in 57 countries and regions. Methods: We utilized an interrupted time series design and IQVIA MIDAS® data to analyze the annual sales data of eight biologic products (adalimumab, bevacizumab, epoetin, etanercept, filgrastim, infliximab, pegfilgrastim, and trastuzumab) across 57 countries and regions from January 1, 2012, to December 31, 2019. We examined the immediate and long-term changes in biologics ex-manufacturer pricing following the entry of biosimilars to the market. Results: Following the entry of biosimilars, the average price per dose of biologic product was immediately reduced by $438 for trastuzumab, $112 for infliximab, and $110 for bevacizumab. The persistent effect of biosimilars' market entry led to further reductions in price per dose every year: by $49 for adalimumab, $290 for filgrastim, $21 for infliximab, and $189 for trastuzumab. Similarly, we analyzed the impact of biosimilars on four biologics' prices in the US, where the prices of three biologics significantly decreased every year, with filgrastim, pegfilgrastim, and infliximab decreasing by $955, $753, and $104, respectively. Conclusions: The introduction of biosimilars has significantly reduced the prices of biologics both globally and in the US. These findings not only demonstrate the economic benefits of increasing biosimilar utilization, but also emphasize the importance of biosimilars in controlling healthcare costs. Policies should aim to expand the availability of biosimilars to counteract the exponential growth of medical spending caused by the use of biologics. [ABSTRACT FROM AUTHOR]

Background/Objectives: The development of biosimilar drugs has revolutionized the management of patients with inflammatory bowel diseases (IBD), significantly reducing healthcare costs. However, the impact of biosimilar availability on patient care is unknown. We conducted a survey to investigate the benefits of using biosimilars in patients with IBD. Methods: Physicians involved in the IBD care were invited to participate in an anonymous online survey. The questionnaire consisted of 42 questions addressing availability, cost, recommendations, and positioning regarding the use of biosimilars. Results: A total of 233 physicians (88.4% gastroenterologists) from 63 countries worldwide participated in the survey. Most respondents had >10 years of practice (202/233, 85.9%). Biosimilars were available in almost all cases (221, 94.8%), and over two-thirds of respondents had more than one biosimilar of adalimumab or infliximab on hospital formulary. In most cases, adalimumab and infliximab biosimilars had a reduced cost of at least 30% compared to the originators. The savings resulting from the use of biosimilars allowed physicians to improve patient care (3/233, 1.3%) or to improve research (2/233, 0.8%) in only a few cases. Interestingly, for about 50% of respondents, the cost of biologics was a limitation for patient access to therapy. For the majority of participants, the availability of biosimilars did not influence treatment decisions in Crohn's disease (70/165, 42.4%) and ulcerative colitis (83/165, 50.3%). Conclusions: The reduced cost of biosimilars compared to reference products is the main driver of choice in IBD. The impact of biosimilars of ustekinumab and vedolizumab in improving access to therapies and changing the treatment algorithm remains to be defined. [ABSTRACT FROM AUTHOR]

Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient's circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to achieve therapeutic drug levels at a faster/similar time compared to the recommended interval. RA patients starting subcutaneous Amgevita or Benepali (adalimumab and etanercept biosimilars, respectively) were recruited and underwent sparse serum sampling for drug concentrations. Drug levels were measured using commercially available kits. Pharmacokinetic data were analysed using a population approach (popPK) and potential covariates were investigated in models. Models were compared using goodness-of-fit criteria. Final models were selected and used to simulate alternative dosing intervals. Ten RA patients starting the adalimumab biosimilar and six patients starting the etanercept biosimilar were recruited. One-compartment PK models were used to describe the popPK models for both drugs; no significant covariates were found. Typical individual parameter estimates were used to simulate altered dosing intervals for both drugs. A simulation of dosing the etanercept biosimilar at a lower rate of every 10 days reached steady-state concentrations earlier than the usual dosing rate of every 7 days. Simulations of altered dosing intervals could form the basis for future personalised dosing studies, potentially saving costs whilst increasing efficacy. [ABSTRACT FROM AUTHOR]

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment. [ABSTRACT FROM AUTHOR]

Objective: To determine the factors, if any, that are associated with the efficacy of "off-label therapies" (OLTs) for multiple sclerosis (MS). Methods: Consecutive patients (N = 174) with relapsing--remitting MS (RRMS) or secondary progressive MS (SPMS) with relapses, on OLTs with a generic formulation of azathioprine, mycophenolate mofetil, or rituximab biosimilar for ≥2 years were included. Annualized relapse rate (ARR) and expanded disability status score (EDSS) 1 year before and ≥2 years after starting OLTs were recorded. Optical coherence tomography (OCT) was done at baseline and at the end of the study. Results: During a median period of 4.1 years (2.4-24), ARR reduced in all (P < 0.0001) and EDSS improved in RRMS (P < 0.0001) patients but not in SPMS (P < 0.31) patients. Good responders were those who had RRMS (P = 0.001, odds ratio [OR] 0.04, 95% confidence interval [CI] 0.01-0.15), female gender (P 0.008, OR 6.67, 95% CI 1.7-26.8), and had early access to OLT (P = 0.006, OR 1.2, 95% CI 1.05-1.40). Baseline peripapillary retinal nerve fiber layer thickness identified the risk of conversion to SPMS (P < 0.01, OR 1.03; 95% CI 1.01-1.06). Conclusions: This limited prospective study suggests that early identification of patients who could potentially respond to unconventional but accessible therapies may be valuable in the treatment of MS, particularly in resource-poor regions. [ABSTRACT FROM AUTHOR]

Introduction: ABP 938 is being developed as a biosimilar candidate to aflibercept reference product (RP), a biologic used for certain angiogenic eye disorders. This study was designed to provide a comparative analytical assessment of the structural and functional attributes of ABP 938 and aflibercept RP sourced from the United States (US) and the European Union (EU). Methods: Structural and functional characterization studies were performed using state-of-the-art analytical techniques that were appropriate to assess relevant quality attributes and capable of detecting qualitative and quantitative differences in primary structure, higher-order structure and biophysical properties, product-related substances and impurities, general properties, and biological activities. Results: ABP 938 had the same amino acid sequence and exhibited similar secondary and tertiary structures, and biological activity as aflibercept RP. There were minor differences in a small number of biochemical attributes which are not expected to impact clinical performance. In addition, aflibercept RP sourced from the US and EU were analytically similar. Conclusions: ABP 938 was structurally and functionally similar to aflibercept RP. Since aflibercept RP sourced from the US and EU were analytically similar, this allows for the development of a scientific bridge such that a single-source RP can be used in nonclinical and clinical studies. Plain Language Summary: Eylea® (aflibercept) is a biologic medication approved for the treatment of patients with certain eye diseases that can result in low vision or blindness. Biosimilars are biologic medications that are highly similar to an existing approved biologic medication, often called a reference product. Biosimilars have the potential to reduce medication costs despite having no clinically significant differences in quality, efficacy, and safety from their reference products. ABP 938 is currently being developed as a biosimilar to aflibercept reference product. We have conducted similarity studies to compare multiple batches of ABP 938 and aflibercept reference product sourced from both the United States and the European Union, using state-of-the-art analytical methods. The results demonstrated that ABP 938 had the same amino acid sequence and similar structural and biological activities as aflibercept reference product. Before biosimilars can be used as medicines, studies such as this one are required by the Food and Drug Administration and other regulatory authorities to ensure that biosimilars are as safe and effective as their reference products. [ABSTRACT FROM AUTHOR]

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In an era of cost pressure, substituting generic drugs represents one of the main cost-containment strategies of healthcare systems. Despite the obvious financial benefits, in a minority of cases, substitution may require caution or even be contraindicated. In most jurisdictions, to obtain approval, the bioequivalence of generic products with the brand-name equivalent needs to be shown via bioavailability studies in healthy subjects. Rare diseases, defined as medical conditions with a low prevalence, are a group of heterogenous diseases that are typically severe, disabling, progressive, degenerative, and life-threatening or chronically debilitating, and disproportionally affect the very young and elderly. Despite these unique features of rare diseases, generic bioequivalence studies are typically carried out with single doses and exclude children or the elderly. Furthermore, the excipients and manufacturing processes for generic/biosimilar products can differ from the brand products which may affect the shelf-life of the product, its appearance, smell, taste, bioavailability, safety and potency. This may result in approval of generics/biosimilars which are not bioequivalent/comparable in their target population or that meet bioequivalence but not therapeutic equivalence criteria. Another concern relates to the interchangeability of generics and biosimilars which cannot be guaranteed due to the phenomenon of biocreep. This review summarizes potential concerns with generic substitution of orphan drugs and discusses potentially problematic cases including narrow therapeutic index drugs or critical conditions where therapeutic failure could lead to serious complications or even death. Finally, we put forward the need for refining regulatory frameworks, with emphasis on Saudi Arabia, for generic substitution and recent efforts toward this direction. [ABSTRACT FROM AUTHOR]

Background: Biosimilars are biologic drugs that have the potential to increase the efficiency of healthcare spending and curb drug-related cost increases. However, their introduction into hospital formularies through initiatives such as non-medical switching must be carefully orchestrated so as not to cause treatment discontinuation or result in increased health resource utilization, such as additional visits or laboratory tests, among others. This retrospective cohort study aims to assess the impact of the introduction of CT-P13 on the healthcare expenditures of patients who were treated with originator infliximab or CT-P13. Methods: Gastroenterology, immunoallergology and rheumatology patients treated between September 2017 and December 2020 at a university hospital in Western Switzerland were included and divided into seven cohorts, based on their treatment pathway (i.e., use and discontinuation of CT-P13 and/or originator infliximab). Costs in Swiss francs were obtained from the hospital's cost accounting department and length of stay was extracted from inpatient records. Comparisons of costs and length of stay between cohorts were calculated by bootstrapping. Results: Sixty immunoallergology, 84 rheumatology and 114 gastroenterology patients were included. Inpatient and outpatient costs averaged (sd) CHF 1,611 (1,020) per hospital day and CHF 4,991 (6,931) per infusion, respectively. The mean (sd) length of stay was 20 (28) days. Although immunoallergology and rheumatology patients had higher average costs than gastroenterology patients, differences in costs and length of stay were not formally explained by treatment pathway. Differences in health resource utilization were marginal. Conclusions: The introduction of CT-P13 and the disruption of patient treatment management were not associated with differences in average outpatient and inpatient costs and length of stay, in contrast to the results reported in the rest of the literature. Future research should focus on the cost-effectiveness of non-medical switching policies and the potential benefits for patients. [ABSTRACT FROM AUTHOR]

In this Policy Forum piece, Robin Feldman discusses how current legislation contributes to informational deficits around drug patents for biologic drugs in the United States. [ABSTRACT FROM AUTHOR]

The binding activity of various trastuzumab biosimilars versus the branded trastuzumab towards the glycosylated extracellular domain of the human epidermal growth factor receptor 2 (HER2) target in the presence of pertuzumab was investigated. We employed size exclusion chromatography with tetra-detection methodology to simultaneously determine absolute molecular weight, concentration, molecular size, and intrinsic viscosity. All trastuzumab molecules in solution exhibit analogous behavior in their binary action towards HER2 regardless of the order of addition of trastuzumab/pertuzumab. This analogous behavior of all trastuzumab molecules, including biosimilars, highlights the robustness and consistency of their binding activity towards HER2. Furthermore, the addition of HER2 to a mixture of trastuzumab and pertuzumab leads to increased formation of high-order HER2 complexes, up to concentrations of one order of magnitude higher than in the case of sequential addition. The observed increase suggests a potential synergistic effect between these antibodies, which could enhance their therapeutic efficacy in HER2-positive cancers. These findings underscore the importance of understanding the complex interplay between therapeutic antibodies and their target antigens, providing valuable insights for the development of more effective treatment strategies. [ABSTRACT FROM AUTHOR]

Biosimilars are biological drugs created from living organisms or that contain living components. They share an identical amino‐acid sequence and immunogenicity. These drugs are considered to be cost‐effective and are utilized in the treatment of cancer and other endocrine disorders. The primary aim of biosimilars is to predict biosimilarity, efficacy, and treatment costs; they are approved by the Food and Drug Administration (FDA) and have no clinical implications. They involve analytical studies to understand the similarities and dissimilarities. A biosimilar manufacturer sets up FDA‐approved reference products to evaluate biosimilarity. The contribution of next‐generation sequencing is evolving to study the organ tumor and its progression with its impactful therapeutic approach on cancer patients to showcase and target rare mutations. The study shall help to understand the future perspectives of biosimilars for use in gastro‐entero‐logic diseases, colorectal cancer, and thyroid cancer. They also help target specific organs with essential mutational categories and drug prototypes in clinical practices with blood and liquid biopsy, cell treatment, gene therapy, recombinant therapeutic proteins, and personalized medications. Biosimilar derivatives such as monoclonal antibodies like trastuzumab and rituximab are common drugs used in cancer therapy. Escherichia coli produces more than six antibodies or antibody‐derived proteins to treat cancer such as filgrastim, epoetin alfa, and so on. [ABSTRACT FROM AUTHOR]

IntroductionPharmaceutical spending accounts for a significant portion of public healthcare budgets. To manage these costs, EU countries implement various cost-containment policies, including competitive tendering for pharmaceuticals. This study examines the impact of EU public procurement regulations on medication procurement practices.MethodsA search for all published tenders of adalimumab in Spain from 2018 to 2024 in the Spanish Public Sector Procurement Database, a period that coincides with the implementation of European legislation and the emergence of adalimumab biosimilars. All available documentation for each tender was reviewed, including the tender offer, technical specifications, specific administrative clauses, appointments of evaluation commissions, supporting memorandum, and evaluation reports.Results and DiscussionOur findings reveal substantial price reductions following the introduction of adalimumab biosimilars, yet highlight significant variability in tender criteria and practices across different regions. Despite adherence to EU directives, the inconsistent application of economic and non-economic factors and an erratic criteria concerning price undermine the intended balance of quality and cost, complicating procurement processes and potentially affecting the availability of a given treatment for patients.

Biosimilars are beginning to gain regulatory approval in the United States. Biosimilars are structurally near identical to the innovator and must demonstrate identical pharmacokinetics via the same binding affinity and biological function on assays. However, biologics are so complex that even the innovator company cannot produce exact duplicates; there is batch-to-batch variation. The International Psoriasis Council has outlined a biosimilarity index, which aims to standardize preclinical definitions of biosimilarity. Such an index, paired with post-approval monitoring, could provide a transparent, quantitative definition of biosimilarity. Such an index could increase trust in biosimilar medicines and the preclinical assessment process without increasing costs. As preclinical analyses are critical to biosimilar approval, manufacturers should devote proportionate resources to completing them. Dermatologists, who might reflexively look for indication-specific clinical data, might also shift their focus to preclinical variables. Finally, it should be noted that biosimilars provide more evidence of similarity than we have for different batches of the innovator product. Thus, any clinical testing standards, or lack thereof, for different batches of innovator products should also apply to biosimilars.

Eleftherios Chatzimichail,1 Kristina Pfau,1,2 Zisis Gatzioufas,1 Georgios D Panos3,4 1Department of Ophthalmology, University Hospital of Basel, Basel, Switzerland; 2Department of Ophthalmology, University Hospital Bonn, Bonn, Germany; 3Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Nottingham, UK; 4Division of Ophthalmology and Visual Sciences, School of Medicine, University of Nottingham, Nottingham, UKCorrespondence: Georgios D Panos, Department of Ophthalmology, Queen’s Medical Centre, Derby Road, Lenton, Nottingham, NG7 2UH, UK, Tel +44 115 924 9924, Email gdpanos@gmail.comAbstract: Ranibizumab, is a humanized, monoclonal antibody fragment that binds and inactivates vascular endothelial growth factor-A (VEGF-A) and VEGF-B. One of the main indications for an intravitreal treatment with ranibizumab is age-related macular degeneration (AMD), which is a retinal disease with a high worldwide socioeconomic impact. Biosimilars constitute biological products that demonstrate similar pharmacodynamic and pharmacokinetic characteristics with a reference product, as well as comparable clinical efficacy, safety and immunogenicity. Since the approval of the first biosimilar Razumab, there has been a variety of new biosimilars available on the market. They offer the advantage of the same good clinical and safety results at a better price. All Ranibizumab biosimilars that have gained approval were tested in double masked Phase 3 clinical studies. The use of Ranibizumab biosimilars in neovascular AMD is well reported in the bibliography. Nevertheless, over the last few years, there is a tendency of using biosimilars in other retinal diseases like retinopathy of prematurity (ROP), diabetic macular edema (DME) or polypoidal choroidal vasculopathy (PCV). In conclusion, ranibizumab biosimilars offer a promising avenue for the management of retinal diseases, especially in countries with lower socioeconomic status, where there is lack of availability of innovator ranibizumab. However, further research is required to fully explore their efficacy, safety, and long-term outcomes in a plethora of retinal diseases.Keywords: ranibizumab, biosimilars, age-related macular degeneration, diabetic macular edema, retinal disorders, retinal vein occlusion, cost-effectiveness

The three-dimensional protein structure is pivotal in comprehending biological phenomena. It directly governs protein function and hence aids in drug discovery. The development of protein prediction algorithms, such as AlphaFold2, ESMFold, and trRosetta, has given much hope in expediting protein-based therapeutic discovery. Though no study has reported a conclusive application of these algorithms, the efforts continue with much optimism. We intended to test the application of these algorithms in rank-ordering therapeutic proteins for their instability during the pre-translational modification stages, as may be predicted according to the confidence of the structure predicted by these algorithms. The selected molecules were based on a harmonized category of licensed therapeutic proteins; out of the 204 licensed products, 188 that were not conjugated were chosen for analysis, resulting in a lack of correlation between the confidence scores and structural or protein properties. It is crucial to note here that the predictive accuracy of these algorithms is contingent upon the presence of the known structure of the protein in the accessible database. Consequently, our conclusion emphasizes that these algorithms primarily replicate information derived from existing structures. While our findings caution against relying on these algorithms for drug discovery purposes, we acknowledge the need for a nuanced interpretation. Considering their limitations and recognizing that their utility may be constrained to scenarios where known structures are available is important. Hence, caution is advised when applying these algorithms to characterize various attributes of therapeutic proteins without the support of adequate structural information. It is worth noting that the two main algorithms, AlfphaFold2 and ESMFold, also showed a 72% correlation in their scores, pointing to similar limitations. While much progress has been made in computational sciences, the Levinthal paradox remains unsolved.

Abstract Introduction Since many biological drug patents have expired, biosimilar agents (BIOs) have been developed; however, there are still some reservations in their use, especially in childhood. The aim of the current study is to evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibitors BIOs as treatment for pediatric non-infectious uveitis (NIU). Methods Data from pediatric patients with NIU treated with TNF inhibitors BIOs were drawn from the international AutoInflammatory Disease Alliance (AIDA) registries dedicated to uveitis and Behçet's disease. The effectiveness and safety of BIOs were assessed in terms of frequency of relapses, risk for developing ocular flares, best-corrected visual acuity (BCVA), glucocorticoids (GCs)-sparing effect, drug survival, frequency of ocular complications, and adverse drug event (AE). Results Forty-seven patients (77 affected eyes) were enrolled. The BIOs employed were adalimumab (ADA) (89.4%), etanercept (ETA) (5.3%), and infliximab (IFX) (5.3%). The number of relapses 12 months prior to BIOs and at last follow-up was 282.14 and 52.43 per 100 patients/year. The relative risk of developing ocular flares before BIOs introduction compared to the period following the start of BIOs was 4.49 (95% confidence interval [CI] 3.38–5.98, p = 0.004). The number needed to treat (NNT) for ocular flares was 3.53. Median BCVA was maintained during the whole BIOs treatment (p = 0.92). A significant GCs-sparing effect was observed throughout the treatment period (p = 0.002). The estimated drug retention rate (DRR) at 12-, 24-, and 36-month follow-up were 92.7, 83.3, and 70.8%, respectively. The risk rate for developing structural ocular complications was 89.9/100 patients/year before starting BIOs and 12.7/100 patients/year during BIOs treatment, with a risk ratio of new ocular complications without BIOs of 7.1 (CI 3.4–14.9, p = 0.0003). Three minor AEs were reported. Conclusions TNF inhibitors BIOs are effective in reducing the number of ocular uveitis relapses, preserving visual acuity, allowing a significant GCs-sparing effect, and preventing structural ocular complications. Trial Registration ClinicalTrials.gov ID NCT05200715.

Background Psoriasis is a chronic immune-mediated systemic disease whose treatment has been revolutionized due to the induction of monoclonal antibody-based biologics. However, access to these drugs has been limited due to their high cost. Biosimilars utilize reverse engineering to create a highly similar product to an originator drug following patent expiration and provide an avenue to reduce costs of biologic treatment. This review seeks to synthesize current knowledge about the development, efficacy, and established benefits of biosimilars, including cost savings and increased access to biologic medicines.Results In 2023, the Veterans Health Administration (VA) generated a cost avoidance of over 67 million dollars through use of 6 currently adopted biosimilars across all indications. There is an opportunity for further cost avoidance, with the pre-set percent discount of statutory contract prices necessary for the adoption of future biosimilars, including adalimumab and etanercept, set at over 50%.Conclusions Biosimilars appear to offer an overall effective, safe, and well-tolerated treatment method for patients with psoriasis and are already providing substantial cost savings within the VA. Additional education is needed to address sources of ambivalence for both patients and providers to assist in further uptake of biosimilars for the treatment of psoriasis.

Repurposing of drugs is a strategy for discovering new uses for already authorized or tested medicines outside their original indications. Bevacizumab is humanized antibody, observed to have anti-VEGF (Vascular Endothelial Growth Factor) effect, which is indicated for colorectal, lung and other types of carcinomas. We conducted research on the historical development and current regulatory status of bevacizumab. In addition, analysis of the data on completed clinical trials with bevacizumab showing potential for repurposing was performed. The analysis for the period 01.01.2019-31.12.2022 found 131 trials, 42 (32%) of which have potential for repurposing. The development and influence of bevacizumab-biosimilar medicines was studied in the whole clinical trials database with biosimilars included in 23 trials (15 in Phase I and 8 in Phase III). The performed research and analysis show that bevacizumab with its pharmacological mechanism of action can affect crucial point in the pathogenesis of different diseases. In addition to this, the process of repurposing can discover new pathways of treatment for patients, shorten the time for reaching the market, lower public healthcare expenses and companies’ budgets. With all the results pointed out, this biotechnological product has potential for repurposing in broad spectrum of new indications.

Biosimilar vaccines and immunotherapeutic are innovative approaches in medical research. This commentary addresses the current disparities in regulations of biosimilar vaccines and immunotherapeutic products across different nations. It also navigates the benefits of global regulatory alignment and challenges that may be encountered. The current discrepancies in regulations across different countries, which pose significant challenges for the development and approval of biosimilar vaccines and immunotherapeutic products. These disparities often lead to delayed market access, increased development costs, and hindered innovation. The commentary stresses that such obstacles could be mitigated through harmonized regulations, resulting in faster approvals, reduced healthcare costs, and improved patient outcomes. Moreover, the commentary explores the specific complexities associated with biosimilar vaccines and immunotherapeutic, such as the intricate evaluation of biosimilarity due to their molecular composition and immunogenic properties. In conclusion, the editorial advocates for collaborative efforts to overcome the challenges in achieving global regulatory harmonization for biosimilars. This includes establishing uniform standards, fostering international cooperation among regulatory agencies, and promoting educational initiatives for healthcare providers and regulators. The ultimate goal is to ensure that patients worldwide have timely access to safe, effective, and affordable biosimilar treatments.

Simple Summary: Protein structure prediction using computer algorithms has long been a challenge; however, the recent introduction of algorithms like AlphaFold2 and ESMFold to predict protein structure has raised the hope for in silico drug discovery, a long sought-after breakthrough. Since the release of these algorithms, it has not been realized whether these algorithms apply if the structure is already reported to be available to the algorithms. Still, the confidence in the predicted structure varies from very low to very high, which is an observation that is unrelated to any physicochemical or biological property of the protein. Any amino acid chain sequence change fails to predict the structure, limiting the utility of these algorithms to an academic exercise. Still, researchers continue to search for the utility of the confidence scores and, despite failing, continue to suggest possible applications, resulting from the logical belief that if the confidence scores are different and reproducible, this must relate to the protein structure. To end this misconception, we predicted the structures of 204 FDA-approved therapeutic proteins, with a wishful thought that the confidence scores, if correlated on this large database, can assist in rank-ordering these proteins for their possible batch-to-batch variability, which could help to reduce testing when these molecules are developed as biosimilars. We also studied modified structures that were not predicted since no reference structure was available for the algorithms to function. This conclusion applies to the two tested algorithms, which showed comparable and proportional confidence intervals. This conclusion is controversial but deserves the attention of researchers who continue to hope to find any drug discovery utility for these algorithms. The three-dimensional protein structure is pivotal in comprehending biological phenomena. It directly governs protein function and hence aids in drug discovery. The development of protein prediction algorithms, such as AlphaFold2, ESMFold, and trRosetta, has given much hope in expediting protein-based therapeutic discovery. Though no study has reported a conclusive application of these algorithms, the efforts continue with much optimism. We intended to test the application of these algorithms in rank-ordering therapeutic proteins for their instability during the pre-translational modification stages, as may be predicted according to the confidence of the structure predicted by these algorithms. The selected molecules were based on a harmonized category of licensed therapeutic proteins; out of the 204 licensed products, 188 that were not conjugated were chosen for analysis, resulting in a lack of correlation between the confidence scores and structural or protein properties. It is crucial to note here that the predictive accuracy of these algorithms is contingent upon the presence of the known structure of the protein in the accessible database. Consequently, our conclusion emphasizes that these algorithms primarily replicate information derived from existing structures. While our findings caution against relying on these algorithms for drug discovery purposes, we acknowledge the need for a nuanced interpretation. Considering their limitations and recognizing that their utility may be constrained to scenarios where known structures are available is important. Hence, caution is advised when applying these algorithms to characterize various attributes of therapeutic proteins without the support of adequate structural information. It is worth noting that the two main algorithms, AlfphaFold2 and ESMFold, also showed a 72% correlation in their scores, pointing to similar limitations. While much progress has been made in computational sciences, the Levinthal paradox remains unsolved. [ABSTRACT FROM AUTHOR]

By definition, biosimilar medicinal products are biological medicinal products that are similar to other biological medicinal products that are already on the market—the reference medicinal products. Access to biosimilar medicines is a current reality. However, to achieve this goal, it is extremely important to consistently and scientifically substantiate the regulatory requirements necessary for biosimilar medicines when accessing the market. Based on an analysis of the raw materials and the type of methods used in the manufacturing processes of biological medicines, it is known that this tends to be more complex for the quality of the finished product than the manufacture of molecules obtained through a chemical process. It is then relevant to highlight the main differences between both products: biological medicines manufactured using biotechnology and the current generics containing active pharmaceutical ingredients (APIs) obtained from synthetic processes. Once arriving at the approval process of these medicinal products, it is imperative to analyse the guidance documents and the regulatory framework that create the rules that allow these biosimilar medicinal products to come to the market. The present review aimed at documenting comparatively the specific provisions of European legislation, through the European Medicines Agency (EMA), as well as the legislation of the United States of America, through the Food and Drug Administration (FDA). This was then translated into a critical appraisal of what concerns the specific criteria that determine the favourable evaluation of a biosimilar when an application for marketing authorisation is submitted to different regulatory agencies. The gathered evidence suggests that the key to the success of biosimilar medicines lies in a more rigorous and universal regulation as well as a greater knowledge, acceptance, and awareness of health professionals to enable more patients to be treated with biological strategies at an earlier stage of the disease and with more affordable medicines, ensuring always the safety and efficacy of those medicines. [ABSTRACT FROM AUTHOR]

Background: Ontario publicly funds reference trastuzumab (Herceptin) and four biosimilar trastuzumab products for adjuvant treatment of HER2+ breast cancer. We assessed the real-world safety and effectiveness of biosimilar trastuzumab compared to Herceptin for adjuvant treatment of patients with HER2+ breast cancer. Methods: This was a population-based, retrospective study comparing the safety and effectiveness of biosimilar trastuzumab and Herceptin for neoadjuvant/adjuvant treatment of HER2+ breast cancer from 2016 to 2021. Treatment patients started biosimilar trastuzumab from November 2019 to June 2021; historical comparator patients started Herceptin from June 2016 to October 2019. Safety outcomes death within 30 days of last dose of trastuzumab, direct hospitalization, emergency department visit leading to hospitalization, early treatment discontinuation, and in-patient admission for congestive heart failure were measured using logistic/negative binomial regression. Overall survival (OS) was measured using Kaplan–Meier methods and Cox proportional hazards regression. Propensity score matching was applied. Results: From June 2016 to 2021, 5071 patients with breast cancer were treated with neoadjuvant/adjuvant trastuzumab. The rate of direct hospitalization (RR: 0.85, 95% CI: 0.74–0.98, p-value: 0.032) was significantly lower in biosimilar compared to Herceptin patients. OS (log-rank test p = 0.98) and risk of mortality (HR: 1.29, 95% CI: 0.72–2.30, p-value = 0.39) did not significantly differ between treatment groups. Conclusions: Biosimilar trastuzumab demonstrated similar safety and effectiveness to Herceptin. The findings can help improve confidence in and use of biosimilars and demonstrate the value of real-world evidence generation for supporting biosimilar implementations and reassessments. [ABSTRACT FROM AUTHOR]

We described insulin glargine (originator) and insulin glargine-yfgn (biosimilar) treatment patterns, assessed effectiveness and safety outcomes, and identified reasons for switching back to the originator product from the biosimilar. This retrospective study included 328,463 Veterans 18 years of age and older who received one or more outpatient prescriptions for insulin glargine and/or insulin glargine-yfgn between 1 June 2021 and 31 December 2022. Patients were assigned to subgroups based on the initial prescription during the study period, prevalent versus incident use for originator insulin glargine, and prior versus no prior use of the originator before the biosimilar (i.e., prevalent originator non-switcher (n = 189,734), originator switch to biosimilar (n = 81,010), incident originator non-switcher (n = 49,401), and incident biosimilar (n = 8318)). There were no differences in the outcome of mean HbA1c (7.9% for all subgroups). There were also no differences in the unadjusted rates of hospitalization and/or emergency room visits for hyper- and hypoglycemia between the prevalent originator non-switcher and originator switched to biosimilar subgroups (p = 0.09 and 0.38, respectively) or the incident originator non-switcher and incident biosimilar subgroups (p = 0.054 and 0.61, respectively). Finally, none of the HbA1c or hyperglycemia outcomes adjusted for baseline characteristics were statistically different. Adjusted analyses for rates of hospitalization and/or emergency room visits for hypoglycemia could not be performed due to the low number of events. Overall, patients who received insulin glargine-yfgn had similar effectiveness and safety outcomes as patients who received the originator. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a relapsing–remitting inflammatory condition that has an increasing incidence across the world, including in the Middle East. Biological monoclonal antibody drugs (biologics) have been shown to be advantageous in treating UC. We undertook a review of the currently available biological and small-molecule therapies, with a particular emphasis on those currently licensed in the United Arab Emirates (UAE). Methods: We conducted a literature search for studies on biological therapies using the PubMed, MEDLINE, and Embase databases using a list of keywords that were generated following referral to existing treatment guidelines for UC. Papers looking at biological and small-molecule treatments for UC in adult populations were included. Pediatric, pregnancy, and cost-effectiveness studies were excluded. Results and Discussion: There are currently three classes of biologics (anti-tumor necrosis factors (anti-TNFs), anti-integrins, and anti-interleukins) and one class of small-molecule therapy (Janus kinase (JAK) inhibitor) licensed for UC treatment in the UAE. Within the anti-TNF class, three medications have been approved: infliximab, adalimumab, and golimumab. For JAK inhibitors, there are two: tofacitinib and upadacitinib. There is only one licensed medication in the remaining classes: vedolizumab (anti-integrin) and ustekinumab (anti-interleukin). The length of studies varied from 6–8 weeks for induction studies and 52 weeks for maintenance studies. The studies demonstrated increased efficacy in these medications compared to placebos when clinical response, clinical remission, and other secondary measures such as mucosal healing were assessed following the induction and maintenance phases. Biosimilars of infliximab and adalimumab are also available for treating UC, and their safety and efficacy were compared to their biologic originators. Conclusions: The introduction of biologics has been proven to be beneficial for the treatment of UC. This review summarizes the efficacy and safety of each biological class in the treatment of the disease; however, biological drug registries and further studies are required to offer more insight into the comparative efficacy and safety of these agents. [ABSTRACT FROM AUTHOR]

Biological therapies have transformed high-burden treatments. As the patent and exclusivity period for biological medicines draws to a close, there is a possibility for the development and authorization of biosimilars. These products boast comparable levels of safety, quality, and effectiveness to their precursor reference products. Biosimilars, although similar to reference products, are not identical copies and should not be considered generic substitutes for the original. Their development and evaluation involve a rigorous step-by-step process that includes analytical, functional, and nonclinical evaluations and clinical trials. Clinical studies conducted for biosimilars aim to establish similar efficacy, safety, and immunogenicity, rather than demonstrating a clinical benefit, as with the reference product. However, although the current knowledge regarding biosimilars has significantly increased, several controversies and misconceptions still exist regarding their immunogenicity, extrapolation, interchangeability, substitution, and nomenclature. The development of biosimilars stimulates market competition, contributes toward healthcare sustainability, and allows for greater patient access. However, maximizing the benefits of biosimilars requires cooperation between regulators and developers to ensure that patients can benefit quickly from access to these new therapeutic alternatives while maintaining high standards of quality, safety, and efficacy. Recognizing the inherent complexities of comprehending biosimilars fully, it is essential to focus on realistic approaches, such as fostering open communication between healthcare providers and patients, encouraging informed decision-making, and minimizing risks. This review addresses the regulatory and manufacturing requirements for biosimilars and provides clinicians with relevant insights for informed prescribing. [ABSTRACT FROM AUTHOR]

The landscape of ulcerative colitis has changed in the last two decades. Advancements in pharmacotherapeutics have heralded the introduction of new treatment options, with many agents in development. Better clinical outcomes are seen with tighter disease control, made possible with greater understanding of inflammatory pathways and their blockade with drugs. There has been a resultant shift in treatment targets, beyond symptoms to endoscopic and histological healing. Controlling the burden of disease activity also lowers the risk of developing colorectal cancer. Colorectal cancer screening now requires the use of dye‑based agents and high‑definition colonoscopy to improve the detection of colonic neoplasms. [ABSTRACT FROM AUTHOR]

Background: From the beginning of the year 2024, gradually implemented amendment to the Medicines Act will enable interchange of biological medicines in pharmacies in Finland. The legislative change aims to reduce health care costs. Methods: Opinions of the biological medicine users regarding substitution in pharmacies and knowledge about biological medicines were determined by a patient survey in community pharmacies and via patient organizations in Finland. Results: In total, 199 users of biological medicines responded to the survey. The respondents did not always know which product they were using, an originator or a biosimilar. This was more prominent among patients with biosimilars determined according to brand names. The more recently the biological medicine had been prescribed, the more likely a biosimilar was in use. Only about 40% of the respondents would enable pharmacies to substitute their biological medicine to a lower cost product. The most common obstacle to the idea of interchange in pharmacies was that the respondents wanted to keep the product the doctor had prescribed for them. In general, biosimilar users were more accepting towards possible interchange than originator users. Conclusion: Although the most recent treatments appear to be initiated with biosimilars, interchange in pharmacies could enable an efficient way to lower health care costs. However, guidance and awareness regarding biosimilars and biological medicines in general would improve patients' willingness towards the change, but also help pharmacists and prescribing doctors in their meaningful role. Plain Language Summary: The use of biological medicines and the costs thereafter are rapidly growing.In Finland, switching between an originator and a biosimilar currently requires doctor's prescription, but interchange in pharmacies will be possible in the beginning of year 2024.Due to notable differences in prices between biological medicines, active switching to lower cost products in pharmacies would restrain health care costs remarkably.Oriola Expert Services ran a survey with an electronic questionnaire among patients using biological medicines.Survey data were collected in pharmacies and via patient organizations.Oriola research team found out that patients do not generally know the differences between biological medicines, and if they are using an originator or a biosimilar.Despite the upcoming pharmacy substitution, future cost savings rely on decisions made by doctors at the time of prescribing biological medication.To ensure patient compliance, sufficient patient information about biosimilars is required. [ABSTRACT FROM AUTHOR]

Background: The utilization of anti-tumor necrosis factor-α (anti-TNF-α) biosimilars in inflammatory bowel disease (IBD) is constantly increasing. However, pediatric data are limited. This study aimed to assess the effectiveness and safety of adalimumab biosimilar (ADL-BioS) in pediatric IBD patients. Methods: All consecutive pediatric IBD patients from the Sicilian Network for Inflammatory Bowel Disease cohort treated with ADL-BioS from 2019 to 2021 were recruited. Remission at weeks 14 and 52, treatment persistence, and adverse events were the endpoints of this study. Factors associated with clinical remission and treatment persistence were examined. Results: There were 41 patients in total. Nine (22%) patients were switched from the reference product to ADL-BioS. Two patients had multiple switches. Eleven months was the median follow-up period. Clinical remission was attained by 70.7% and 72.0% of patients on weeks 14 and 52, respectively. Four (9.8%) adverse events occurred (10.1/100 person-year). Treatment persistence was 85.4% at 1 and 2 years. Patients with a longer duration of disease had a higher probability of stopping their treatment (p = 0.036). Conclusions: This is the first real-world study that particularly addresses the use of ADL-BioS in pediatric IBD. With high rates of treatment persistence and a low frequency of non-serious side effects, ADL-BioS seems to be effective. [ABSTRACT FROM AUTHOR]

Objective: Transitions to biosimilars are common to reduce the cost burden of biologics. While brand changes can be daunting for patients, few studies have explored patients' experiences with the transitioning process. This study examined rheumatology patients' experiences with a mandatory nationwide brand change to an adalimumab biosimilar. Methods: People with rheumatic diseases involved in the adalimumab transition in Aotearoa New Zealand completed a nationwide online survey. Participants (n = 117, 48% with rheumatoid arthritis) reported their satisfaction with the biosimilar, logistics and supply, information and communication, and availability of support. They also reported what did and did not go well during the transition and provided recommendations for future transitions. Results: The mean [SD] satisfaction score with the transition was 6.2 [3.2] on a 0‐10 scale, with 10 indicating high satisfaction. Participants were the least satisfied with the support and information from patient support organizations, and training for the device during the transition. Participants were most satisfied with the biosimilar supply, support from pharmacists, and how early they were informed before the transition occurred. After the transition, participants were less satisfied with the device quality, patient support program, biosimilar safety and efficacy, and the provision of alcohol wipes and sharps bins (p < 0.05 for all). Satisfaction with training for the biosimilar device (B =.25, p =.036) predicted overall satisfaction. Participants appreciated less injection pain and the ease of the biosimilar device. The lack of alcohol wipes and loss of the bio‐originator support program were viewed negatively. Conclusion: Future biosimilar transitions should ensure the availability of alcohol wipes, sharps bins, and a comparable patient support program. Patient support organizations could be involved in providing information to patients about the change. [ABSTRACT FROM AUTHOR]