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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.

Background: Biosimilars have the potential to save a significant amount of money in cancer treatment costs. However, barriers exist in the adoption of biosimilar products. Japan introduced a new health policy in 2022 to promote the use of biosimilars in oncology by offering financial incentives to eligible hospitals. This study aims to examine the association between these financial incentives and prescription patterns. Methods: The study analyzed Diagnosis Procedure Combination (DPC) data to assess the impact of the new health policy on the use of biosimilar products in oncology. The policy provided an additional fee for hospitals using biosimilar products. The study included patients with specific types of cancer and analyzed the proportion of monthly biosimilar prescriptions using the number of prescriptions of reference and biosimilar products. A generalized synthetic control method was used for analysis. Results: From April 2020 to March 2023, the study involved 27,737 patients in 114 hospitals, with 63 eligible hospitals receiving financial incentives. The average number of prescriptions of the drugs (rituximab, trastuzumab, and bevacizumab) increased gradually in both eligible and ineligible hospitals. The financial incentives were associated with a significant increase in the proportion of biosimilar product prescriptions, with a monthly increase of 0.092 per month (95% CI, 0.040–0.145) [9.2%, 95% CI, 4.0–14.5] compared to ineligible hospitals. Conclusion: Our study indicates that providing financial incentives to hospitals to utilize biosimilar products increased their prescriptions. Japan's recent health policy of moderate financial incentives is an effective approach to increasing prescriptions of biosimilar products. [ABSTRACT FROM AUTHOR]

The development of pharmaceutical products is the critical bridge that moves a potential new medicine from academic discovery to applied treatment of patients. It translates an idea for a new drug to bench-level research on how it can be manufactured, formulated, characterized and controlled for use in non-clinical and early clinical trials. From pre-clinical R&D discovery work through the commercial launch, substantial R&D CMC data is generated to develop and optimize cGMP manufacturing and testing operations, while also supporting product comparability, elucidating product / impurity structures, assessing critical quality attributes, developing the drug delivery mode, and developing the product formulation for long-term stability. Significant R&D CMC work continues post-approval to support continuous improvement and market expansion of the commercial product. These activities are crucial elements of Product Lifecycle Management, and taken together, they comprise Pharmaceutical Quality or Chemistry, Manufacturing and Controls (CMC). The objective of this paper is to mitigate the regulatory ambiguity of R&D quality systems with practical, risk-based examples and recommendations when conducting supportive CMC studies for biological products. Making sound strategic CMC decisions under any circumstances assumes data from R&D studies are reliable, traceable, and complete. While there are specific regulatory guidelines on phase-appropriate cGMP activities, none exist for quality practices in R&D CMC laboratories conducting non-cGMP studies. Hindsight is not the time to discover that R&D studies lack key elements that would otherwise have allowed the data to be directly presented to regulators, if needed. There is a strong prospective business interest in protecting considerable investments made for CMC R&D studies. Therefore, establishment of a robust and stage-appropriate R&D laboratory quality system is essential for companies seeking to capitalize on prior knowledge, protect investments, and be prepared for accelerated approval pathways. [ABSTRACT FROM AUTHOR]

Unlike small molecule drugs and generic products, the active component of biologics and biosimilars are not identical chemical entities. Despite bioequivalence, there is limited evidence in clinical practice (i.e. Phase IV post-marketing surveillance) regarding the safety of biosimilar rituximab and even less so for "switching therapy" with respect to safety. Drug substitution by switching aims to realise cost savings by changing therapy involving a reference (biologic) product to a biosimilar. A retrospective analysis of safety outcomes including treatment-emergent adverse effects (TEAEs), rates of death and discontinuation of therapy, for all patients that received switching therapy (from reference to biosimilar rituximab, n = 33) was compared to patients who did not did not switch therapy (received biosimilar rituximab only, n = 18) at an Australian metropolitan cancer centre, over a six-month period. There was no statistical significant differences for any safety outcomes examined. Switching therapy for patients receiving rituximab does not lead to poorer safety outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Biosimilars are anticipated to be widely used in the treatment of rheumatoid arthritis (RA), owing to their cost efficiency; LBEC0101 was the first etanercept (ETN) biosimilar approved in Japan. However, there are limited real-world data comparing its safety and effectiveness with those of a reference product. Methods: This study used data from the Kyoto University Rheumatoid Arthritis Management Alliance cohort, including patients with RA who received ETN therapy—ETN reference product (ETN-RP) or LBEC0101—between 2015 and 2021. Serum ETN levels were measured using liquid chromatography–tandem mass spectrometry. Results: The 1-year continuation rates of ETN-RP and LBEC0101 were 58.7% and 74.4%, respectively. Effectiveness of treatment was evaluated in 18 patients; both products significantly reduced the 28-joint RA disease activity score and erythrocyte sedimentation rate (DAS28-ESR). Moreover, to determine equivalence, we analysed 11 patients who switched from ETN-RP to LBEC0101; the DAS28-ESR and serum ETN levels before and after switching were not significantly different. Conclusions: This real-world cohort study confirmed that the biosimilar of ETN, LBEC0101, was comparable to the reference product in terms of continuation rate, effectiveness at initiation of introduction, and effect persistence before and after switching in clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this article is to update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA). Methods: We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, two independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses. Results: Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to conventional synthetic DMARD (csDMARD). Rituximab with and without concomitant csDMARDs showed similar efficacy to other biological DMARDs (bDMARDs) in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients. Conclusions: This systematic review provides latest evidence for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for RA management. [ABSTRACT FROM AUTHOR]

Background: In 2018, the French government introduced two mutually exclusive financial incentives to increase etanercept and insulin glargine biosimilar use. The general case redirects 20% of the price difference between the reference product and its biosimilars to hospitals for every biosimilar dispensed in community pharmacies from hospital prescriptions. The experimental case redirects 30% to prescribing clinical units after hospital selection. Adalimumab was added to these incentives in 2019, after its first biosimilar was launched. Objective: This retrospective observational study aimed to compare both general and experimental incentives after 19 months to assess the impact of directly incentivizing clinical units for adalimumab biosimilars. Method: The monthly number of adalimumab boxes dispensed in community pharmacies was linked to the corresponding hospital's prescription using IQVIA Xponent data from November 2017 to October 2020. The monthly mean rate of adalimumab biosimilars was compared between incentive groups and subgroups depending on hospitals' prior experience with the etanercept experimental case. Results: General case hospitals had a significantly lower mean biosimilar uptake (16.7% vs 23.2%, p = 0.029) than those included in the experimental case. Twenty-three of the 40 hospitals in the experimental case and ten out of the 91 hospitals studied in the general case had already taken part in the etanercept experiment. Biosimilar uptake was higher, but not statistically significant, for hospitals with prior experience in the adalimumab general case group (p = 0.086). Conclusions: This study confirmed that incentivizing close to physicians was more effective in increasing the biosimilar rate. It also suggested that previous incentive experience positively influenced biosimilar penetration. [ABSTRACT FROM AUTHOR]

Introduction: The advent of bevacizumab has considerably transformed the therapeutic landscape for non-small cell lung cancer (NSCLC) patients devoid of specific genetic mutations. A pivotal milestone has been reached with the recent approval of a bevacizumab biosimilar, following rigorous phase III clinical investigations, poised to augment NSCLC therapeutic strategies. Methods: This retrospective analysis encompasses a large-scale study conducted between January 2021 and December 2023, involving 1058 NSCLC patients (metastatic or locally advanced stages). The research design entailed a comparative assessment of the safety and efficacy profiles of combined therapies using the original bevacizumab and its biosimilar, adhering to RECIST v1.1 criteria. Adverse event grading was standardized using the National Cancer Institute’s CTCAE v5.0. Results: Notably, the biosimilar demonstrated an objective response rate (ORR) of 29.79% in 606 patients, closely paralleling the 27.41% ORR observed in 452 patients receiving the original drug, with insignificant risk differences (-0.03) and a risk ratio of 0.987, affirming equivalence. Progression-free survival (PFS) was influenced by radiation status, treatment lines, and regimen combinations, while dosage intensity and genetic factors had negligible impacts. The incidence of treatment-emergent adverse events (TEAEs) was slightly higher in the biosimilar group (75.11%) versus the original drug group (72.78%), with grade 3 or more severe TEAEs occurring in 23.6% and 18.5% of patients, respectively (Detailed criteria for the definition and assessment of TEAEs have been added to the Methods section, including the use of the National Cancer Institute’s CTCAE v5.0 for grading). Conclusions: The study affirms that bevacizumab biosimilars offer equivalent therapeutic efficacy and a similar safety profile to the originator product in the management of locally advanced or metastatic NSCLC. The tolerability of the toxicity profile, coupled with the absence of unforeseen adverse reactions, underscores the viability of biosimilar bevacizumab as a valuable addition to NSCLC treatment regimens. These findings also imply potential benefits for a broader patient population beyond clinical trial confines through the adoption of biosimilar beta-adrenergic blocking agents. [ABSTRACT FROM AUTHOR]

Aim: To describe patient and treatment characteristics associated with bevacizumab BS-Pfizer, rituximab BS-Pfizer and trastuzumab BS-Pfizer and their reference products in Japan. Methods: This retrospective observational study used an administrative claims database to identify patients with ≥1 biosimilar or reference product prescription from 2019 to 2022 for approved indications. Descriptive statistics were calculated. Results: Overall, 14–39% of biosimilar-prescribed patients initiated therapy with reference products. Biosimilar utilization significantly increased from 2019 to 2022. The most-commonly prescribed concomitant class of therapy with biosimilars was antineoplastic therapy. Conclusion: Reference products were most frequently prescribed among the Japanese cohorts, but substantial and increasing proportions received biosimilars over time. Future studies should extend our initial insights to assess biosimilar clinical outcomes in Japanese settings. Plain Language Summary This study examines the adoption of cancer biosimilar therapies in Japan from 2019 to 2022. Cancer biosimilars are complex treatments that closely resemble established cancer therapies already available in Japan. We looked into the characteristics of patients receiving three specific biosimilars – bevacizumab BS-Pfizer, rituximab BS-Pfizer and trastuzumab BS-Pfizer. We also investigated where patients received biosimilar treatment, other therapies they received alongside biosimilars and the proportion of patients using these therapies each year during the study. Our analysis utilized data from the 'Medical Data Vision' database, which records care provided in hospitals across Japan. We analyzed patient demographics and treatment patterns, and compared different groups using statistics to identify significant differences. Notably, we observed that between 14 and 39% of patients initially started treatment with the original version of the drug on the market, known as the 'reference product,' before switching to the biosimilar. Furthermore, our findings revealed a significant increase in the use of biosimilars each year during the study period. Biosimilars were most-commonly used alongside chemotherapy drugs. These initial findings shed light on the patient population using cancer biosimilars in Japan and the treatment contexts in which they are utilized. Future research should delve deeper into aspects such as cost of care, patient survival, side effects and other pertinent factors related to the use of biosimilars in cancer care in Japan. Article highlights The use of oncology biosimilars in clinical practice in Japan is limited, at least partly, by the lack of evidence demonstrating real-world outcomes in Japanese patients. This retrospective observational study provides descriptive insights into the real-world use of bevacizumab, rituximab and trastuzumab biosimilars in Japan for colorectal cancer and non-small-cell lung cancer, B-cell non-Hodgkin's lymphoma and HER2-positive breast and gastric cancers, respectively. We observed significant increases in biosimilar utilization over time from 2019 to 2022. Across indications, from 14 to 39% of biosimilar-prescribed patients switched to the biosimilar after initiating therapy with the corresponding refence product. The most commonly prescribed concomitant class of therapy with biosimilars was antineoplastic therapy across each setting. This study has several limitations that should be noted, including that the Medical Data Vision hospital-based claims database has missing data for some variables, lacks detailed diagnosis and prognosis data (histology, Eastern Cooperative Oncology Group performance status, disease severity, etc.) and does not record deaths that occur outside the hospital. Initial real-world insights in Japan demonstrate comparable patient characteristics, treatment patterns and treatment duration between bevacizumab, rituximab and trastuzumab biosimilar and originator-treated patients. [ABSTRACT FROM AUTHOR]

Introduction: Pharmaceutical 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. Methods: A 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 Discussion: Our 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. [ABSTRACT FROM AUTHOR]

During the last two decades, an increased number of molecules with multiple mechanisms of action have been approved for the treatment of inflammatory bowel disease (IBD), with a substantial increase in the costs related to therapy, which has become a concern for payers, regulators, and healthcare professionals. Biosimilars are biologic medical products that are highly structurally similar to their reference products; have no clinically meaningful differences in terms of immunogenicity, safety, or effectiveness; and are available at a lower price. Materials and Methods: This was an observational prospective study conducted in two IBD centres in Bucharest and included 53 patients, 27 male (M) and 26 female (F), diagnosed with IBD according to standard clinical, endoscopic, radiological, and histological criteria, who were non-medically switched at the indication of the National Insurance House to a biosimilar of Adalimumab. Aims: The aim was to determine the rates of clinical remission, adverse effects, and treatment persistence at one year. Results: No significant differences were found in terms of the faecal calprotectin (FC) and C-reactive protein (CRP) levels 6 and 12 months after changing from the originator biologic treatment to a biosimilar. Only one patient required a change in their biological treatment following the clinical and biological loss of response. The main adverse effect reported by the patients was pain at the injection site. Of the 53 patients, only 2 reported pain at the injection site, and 1 patient reported experiencing abdominal pain and rectal bleeding immediately after the switch, but no recurrence was observed clinically or endoscopically. Conclusions: This observational study is the first to be carried out in Romania that shows that, after a non-medical switch, biosimilars of Adalimumab are as efficient and safe as the originator Adalimumab in the clinical treatment of patients with IBD. [ABSTRACT FROM AUTHOR]

Simple Summary: This study analyzes the use of rituximab (RTX) in the daily clinical practice of several Italian oncohematology centers, with a particular focus on the adoption of biosimilars. The results show that only a minority of patients (22%) switched between different biosimilars, while the majority continued treatment with the biosimilars Rixathon and Truxima. This finding suggests that the proactive sharing of guidelines between regulators and prescribers, from the outset, may be an effective strategy to further promote the adoption of biosimilars. This approach could be particularly useful in those areas where the use of biosimilars is still lower than the national average, helping to free up economic resources that could be redirected towards other healthcare opportunities. The clinical safety and efficacy of rituximab biosimilars compared to the reference rituximab (Mabthera) have been well established in randomized trials. However, concerns persist regarding the safety of changing from the reference product to biosimilars, and particularly between different biosimilars. This prospective multicenter observational study was conducted in 13 oncohematology units of eight Italian regions. The study included 800 patients with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) who received rituximab between March 2018 and June 2022. To minimize survivorship bias, only newly diagnosed patients (i.e., those without prior rituximab treatment) were included in the analysis of adverse drug reactions (ADRs). Thus, this study focused on 505 incident cases (79.8% of the initial cohort) from 13 centers. A total of 3681 rituximab infusions were administered, and 16.8% of the patients experienced at least one ADR. These were observed most frequently during the first infusion (44 patients, 52%) and the second infusion (17 patients, 20%). The most frequent reactions were general disorders and administration site conditions (n. 50, 8% serious). These findings support the clinical safety of rituximab biosimilars and suggest that switching between biosimilars does not increase the risk of adverse events. This evidence may alleviate concerns about biosimilar use, potentially leading to broader acceptance and reduced healthcare costs. [ABSTRACT FROM AUTHOR]

Technological advances in analytics, as well as scientific and regulatory knowledge and experience gained from biosimilar development/approvals over the last decade, enabled the World Health Organization (WHO) in 2022 to revise its guidelines on the evaluation of biosimilars. Among the revisions, there is more reliance on analytical and functional aspects to prove similarity (and likely fewer clinical requirements). WHO international reference standards for biosimilars provide additional confidence to regulators looking for evidence‐ and data‐based regulatory convergence in scientific and technical measures of quality attributes. These standards serve as a benchmark for harmonizing the bioactivity or potency of biosimilars, ensuring their future sustainability. This article discusses the availability and role of WHO international reference standards throughout the product life cycle of biosimilars. [ABSTRACT FROM AUTHOR]

Background: Patient satisfaction has been positively associated with adherence which is expected to impact outcomes. Although vital for successful implementation of biosimilar medicines, little is known about the patient perspective of transition. Aim: The aim of this study was to investigate clinical outcomes and patient experience of transitioning between reference adalimumab and a biosimilar (SB5). Method: iBaSS is a phase IV single-centre, prospective, randomised, single-blind, cross-over study in adult subjects with Crohn's disease. Participants, stable on adalimumab before consent, received 24 weeks of treatment with both reference adalimumab and SB5. The primary outcome was the proportion of patients maintaining baseline clinical status throughout each treatment period, with patients' perspective of disease control and treatment satisfaction assessed as secondary outcomes. Results: A total of 112 participants, representative of the heterogeneous patient populations encountered in routine clinical practice, were enrolled. A similar proportion of participants maintained baseline clinical status through each treatment period: 81.8% with reference adalimumab and 79.5% with SB5. Patient reported outcomes (IBD-Control questionnaire (SB5: 15.5; reference adalimumab 15) and TSQM), adverse events and therapeutic drug monitoring remained consistent through both treatment periods, although a higher median injection pain VAS score was noted with SB5 (53/100 versus 6/100 with reference adalimumab). The number of switches undertaken in the study did not impact serum drug concentration or immunogenicity. Conclusion: This study, mimicking real world adalimumab transition, demonstrates that patients undertaking brand transition can be expected to have consistent clinical and satisfaction outcomes. Clinical trial registered with EudraCT: Number 2018–004967-30 [ABSTRACT FROM AUTHOR]

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]

Background: While Pegaspargase is an essential component of the treatment of acute lymphoid leukemia (ALL) in children, it causes adverse events (AEs) that sometimes make full use impossible. Objective: The objective was to investigate the safety of Pegaspargase biosimilar in pediatric ALL patients undergoing treatment according to ICiCLe ALL-14 protocol. Method and Materials: A prospective study was carried out in a university teaching hospital located in the state of Maharashtra, India. Data on clinical factors and adverse reaction characteristics were gathered from hospital medical records. Suspected AEs were classified according to causality and severity. Results: During the study period, 72 children had 52 suspicions of AEs during treatment with biosimilar Pegaspargase. The odds ratio of 1.11 (95%CI, 0.41–2.98) suggested that males and females were both equally likely to experience adverse drug events, despite the fact that the frequency of suspected AEs was higher in boys (66%) than in girls (33%). None of the patients experienced allergic reactions. The high-risk category had the highest number of suspected AEs (56%), followed by intermediate risk (20%) and standard risk (20%). These patients showed a high frequency of suspected AEs during the induction phase (43%) followed by the consolidation phase (26%). Sixty percent of the reactions were classified as grade 1 or 2. ALL cell type (p = 0.02), risk category (p = 0.04) and length of hospitalization (p = 0.003) were significantly correlated with suspected AEs. Conclusion: Bio-similar Pegaspargase in combination with chemotherapy was safe and tolerable in the pediatric ALL patients treated according to ICiCLe ALL-14 protocol. Suspected AEs ranged from mild to moderate and hepatic failure and hyperglycemia being severe. [ABSTRACT FROM AUTHOR]

Background and Objective: Biological medicinal products improve patients' lives, but access is limited, mainly due to high costs. Patents for many existing biological products are expiring, and generic versions, which are referred to as biosimilars, are produced to serve as an alternative to the reference medicinal product (RMP) cutting down the costs and expanding access. The present paper assesses the analytical similarity between Formycon's FYB206 pembrolizumab biosimilar candidate and Keytruda®, an RMP that is approved to treat various types of cancer, with the intention of determining FYB206's suitability to enter clinical biosimilar trials. Methods: Monoclonal antibodies (mAbs) are biological medicinal products that are characterized by a high overall heterogeneity. Due to the complex nature of these molecules, a comprehensive comparative analytical assessment was designed to demonstrate analytical similarity in all clinically relevant quality attributes between RMP and the corresponding biosimilar candidate. This exercise addresses physicochemical, biophysical as well as functional characteristics. Results: The comparative analytical evaluation results demonstrate that the proposed biosimilar is structurally and functionally highly similar to the RMP, showing only minor differences for some quality attributes that are justified to be noncritical for clinical efficacy and safety. Conclusion: Based on physicochemical and biological characteristics, FYB206 is suitable to enter the clinical phase. [ABSTRACT FROM AUTHOR]

Biologics, including adalimumab, are some of the most expensive medications in the United States. This study set out to predict the changes in pricing and access to adalimumab after losing patent exclusivity by investigating market trends for other biosimilars that have lost exclusivity. Center for Medicare and Medicaid Services Medicare spending data from 2017 to 2021 was utilized to investigate market trends for several branded biologics and their biosimilars. Changes in cost per unit, total beneficiaries on the brand and change in total beneficiaries on brand or biosimilar were analyzed. Over this time frame with no competitor, branded adalimumab had a 72% cost per unit increase and 23% increase in total beneficiaries. Branded infliximab with competitors had a 53% cost reduction, 26% reduction of beneficiaries on the branded medication and a 1% decrease in beneficiaries on any form of infliximab, branded or biosimilar. Likewise, most other medications investigated showed a reduction in cost per unit and number of beneficiaries on the brand with a mixed trend in overall beneficiaries on any form of the medication. These trends indicate that biologics losing exclusivity, such as adalimumab, lead to a cost decrease with a loss in market share as expected. However, it is unknown if accessibility and affordability of these medications is changing as a corresponding increase in total beneficiaries on any form of the medication is not seen as might be expected with lower cost alternatives entering the market. [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]

Purpose: To describe, compare similarity of pharmacokinetic (PK), pharmacodynamic (PD) and efficacy of SB12 and reference eculizumab (ECU) and find clinically significant covariate relationships. Methods: The PK, PD (terminal complement activity) and efficacy (LDH) data of SB12 and ECU were obtained from 289 subjects from phase I and phase III studies. One- and two-compartment PK models with first-order elimination were evaluated for SB12 and ECU. For PD and efficacy, both direct and indirect models were tested. The impact of covariates on PK, PD and efficacy parameters was assessed. Relationship between PK/PD and PD/efficacy was characterized. This modeling was performed using NONMEM version 7.4 (Icon Development Solutions, Ellicott City, MD, USA). Results: The two-compartment model adequately described the PK of SB12 and ECU, and the subject's weight was chosen as a clinically significant covariate affecting drugs' clearance and central volume of distribution. Treatment group was not a significant covariate affecting clearance. The direct response model using inhibitory sigmoid Emax and sigmoid Emax relationship well described the PK/PD relationship and PD/efficacy relationship of SB12 and ECU, respectively. Through this modeling, the relationships between PK, PD and efficacy were characterized. There were no differences in PK, PD and efficacy parameters between SB12 and ECU in pooled populations of healthy subjects and paroxysmal nocturnal haemoglobinuria (PNH) patients. Conclusion: The population modeling showed PK, PD and efficacy similarities between SB12 and ECU in pooled population of healthy subjects and PNH patients, supporting the totality of evidence on biosimilarity for SB12. [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]

Biosimilars are a new category of medicines that have revolutionized the treatment of patients with life-threatening conditions, such as cancer and autoimmune diseases. A biosimilar is a biological product that is very similar to an already approved biological medicine that is used as its reference. These medicines go through less clinical studies than their reference product and therefore the cost of their development process is significantly lower, giving patients access to them more quickly and at a more affordable price. However, due to the structural complexity and inherent degree of variability of these products, it is very difficult to develop biosimilar medicines that are exactly the same as the reference product. Thus, it is extremely important to define strict controls to guarantee that these minor differences are not clinically significant in terms of safety and efficacy. Like any other medicine, biosimilars have to go through a complex approval process, which involves a thorough assessment by regulatory authorities to ensure these products meet the necessary standards of quality, safety, and efficacy before being placed on the market. Due to their nature and complexity, the approval process of biosimilar medicines contains some unique and specific considerations. This review aims to address the regulatory framework of biosimilar medicines, their development process and the approval requirements by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA). [ABSTRACT FROM AUTHOR]

Background: There have been only few reports on Rhupus syndrome with severe visceral involvement. Moreover, there was little consensus regarding its treatment. Belimumab is one of the options for treating this disease. For patients with clinical symptoms and elevated levels of anti CCP antibodies and anti-double stranded DNA antibodies, and it suggests Rhupus syndrome. After effective treatment, the decrease in levels of anti CCP antibodies and anti-double stranded DNA (ds-DNA) antibodies can effectively delay the progression of the disease and protect target organs. Methods: We used a chemiluminescence instrument, (Yahuilong; Shenzhen, China), to measure the changes in CCP and dsDNA before and after treatment. Results: Prior to treatment, the patient presented with symptoms of rheumatoid arthritis and systemic lupus erythematosus. Her laboratory tests showed dsDNA (214 IU/mL) and CCP level of ˃ 3,000 U/mL. After treatment with belimumab, the clinical symptoms were significantly relieved, and the patient's CCP IgG level decreased to 263.5 U/mL. A blood test found that her anti-dsDNA was negative. Conclusions: CCP and dsDNA can serve as indicators for the diagnosis and treatment of Rhupus syndrome. [ABSTRACT FROM AUTHOR]

In this paper, we explore dynamic market share and public healthcare costs of trastuzumab's evergreening (subcutaneous) variant during introduction of trastuzumab's competitive biosimilar variants in the Netherlands. We used a time series design to assess dynamic market share of trastuzumab's evergreening variant after introducing trastuzumab's biosimilar variants, focusing on the number of treatments and patients. The public healthcare costs of this evergreening strategy were estimated using administrative claims data. Our results show that the original trastuzumab was completely replaced by the subcutaneous and biosimilar variants. The uptake of the subcutaneous form peaked at 50% market share but after the introduction of biosimilars progressively reduced to a market share of 20%, resulting in a more competitive market structure. The public healthcare costs for trastuzumab significantly decreased after the introduction of the biosimilars. After the introduction of the biosimilars, a substantial price drop is visible, with the subcutaneous version, still under patent, also falling sharply in price but less strongly than the iv/biosimilar version. As the costs are publicly funded, we recommend a more explicit societal debate to consider if the potential benefits of subcutaneous Herceptin® (and other similar medicines) are worth the additional costs, and at which price it should be reimbursed as the part of the benefit package. [ABSTRACT FROM AUTHOR]

Introduction: The management of Crohn's disease (CD) in the Middle East, like in other parts of the world, is rapidly evolving with the introduction of novel advanced medical and biological therapies. In the United Arab Emirates (UAE), several biological therapies are used to achieve remission in severe and resistant cases of CD. We carried out a literature search to analyze the effectiveness and safety of biologic treatments currently licensed in the UAE. Methods: We searched the PubMed, Embase and Cochrane library databases from inception to January 2020 to identify relevant studies. Search terms were generated using established treatment guidelines for CD. We also manually searched the bibliographies of relevant literature to obtain additional papers. Results: Biologic and small molecule agents for CD include four core drug classes: anti-tumor necrosis factor-α agents (TNF-α), integrin receptor antagonists, Janus kinase (JAK) inhibitors and IL-12/IL-23 antagonists. All drug classes showed good efficacy and safety in managing patients with CD. Some drug classes had distinguishable side effect profiles. This included an increased lymphoma and tuberculous risk for TNF-α and integrin receptor antagonists. Many trials supported the effectiveness of these licensed drugs. Biologic agent intolerance was common; one-third of patients receiving TNF-α treatment will develop intolerance to that specific drug. Conclusions: Advanced medical therapies licensed in the UAE have proven to be safe and efficacious. Additional research is required to evaluate the safety and efficacy of newer biologics and biosimilars. [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 and Objective: Biological medicinal products improve patients' lives, but access is limited, mainly due to high costs. Patents for many existing biological products are expiring, and generic versions, which are referred to as biosimilars, are produced to serve as an alternative to the reference medicinal product (RMP) cutting down the costs and expanding access. The present paper assesses the analytical similarity between Formycon's FYB206 pembrolizumab biosimilar candidate and Keytruda®, an RMP that is approved to treat various types of cancer, with the intention of determining FYB206's suitability to enter clinical biosimilar trials. Methods: Monoclonal antibodies (mAbs) are biological medicinal products that are characterized by a high overall heterogeneity. Due to the complex nature of these molecules, a comprehensive comparative analytical assessment was designed to demonstrate analytical similarity in all clinically relevant quality attributes between RMP and the corresponding biosimilar candidate. This exercise addresses physicochemical, biophysical as well as functional characteristics. Results: The comparative analytical evaluation results demonstrate that the proposed biosimilar is structurally and functionally highly similar to the RMP, showing only minor differences for some quality attributes that are justified to be noncritical for clinical efficacy and safety. Conclusion: Based on physicochemical and biological characteristics, FYB206 is suitable to enter the clinical phase. [ABSTRACT FROM AUTHOR]

Abstract Background The Chinese biosimilar industry has demonstrated rapid growth in recent years. Limited evidence is available about biosimilar uptake at the national level. This study aimed to assess biosimilar uptake in the case of trastuzumab and to explore potential factors influencing the biosimilar penetration at national and provincial levels. Methods This study employed an interrupted time series analysis to assess the level and trend changes of national trastuzumab originator consumption and the overall trastuzumab consumption after the price reduction of the originator and the introduction of the first biosimilar using the China Hospital Pharmacy Audit procurement data from March 2018 to February 2023. A latent class trajectory model (LCTM) was also adopted to estimate the biosimilar penetration across 30 provincial-level administrative divisions (PLADs). Based on the LCTM grouping results, provincial characteristics were analyzed. Results After rapid growth, the penetration of biosimilars demonstrated a moderate ascending trend at the national level, reaching 27% in February 2023. Following the introduction of the first biosimilar in July 2021, the consumption of the originator decreased by 0.5% per month (P = 0.008), and the growth rate of overall trastuzumab consumption decreased by 1.1% per month (P = 0.014). LCTM fit the best when the number of trajectory classes was two, dividing 30 PLADs into a group demonstrating a faster increase in biosimilar penetration and the other with a slower increase. The PLADs in the fast-increasing group had a higher proportion of the population covered by the national basic health insurance, a lower proportion of the urban population, a lower proportion of the population covered by the urban employee health insurance program, a lower gross domestic product per capita, a lower total health expenditure per capita, and a lower out-of-pocket expenditure. Conclusions The uptake of trastuzumab biosimilars in China was lower compared with major European countries. The introduction of trastuzumab biosimilars presented a substitutional effect. Perceptions of physicians and patients, the medicines procurement model, competition from other biologics, and health insurance payment methods may influence biosimilar uptake. Enhancing a comprehensive understanding of biosimilars among physicians and patients, including biologics with biosimilars in the national pooled procurement, and implementing provider payment reforms could foster biosimilar penetration.

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.

Background: Monoclonal antibodies (mAbs) are agents that are clones of homogenous parent B cells used in managing and diagnosing multiple conditions. They are used for individualized therapy for patients due to their high specificity for an antigen/epitope. Much needs to be understood about their utilization patterns in a developing country like India, where accessibility and cost play a major role in patient care. Objectives: The objectives of this study were to evaluate the drug prescribing patterns and indications for use of mAbs and compare their availability, with the essential drug list of the World Health Organization (WHO) and the National list of essential medicines in India (NLEM). Materials and Methods: This is a retrospective cross-sectional study conducted from July to December 2021. Data were collected from 237 patients who have visited the tertiary care center or been admitted and have received mAbs. Demographic data, department of admission, diagnosis on admission, and mAbs used during treatment were recorded and analyzed. Results: Out of the 237 patients, who were eligible for this study, 61.6% of them were males and 38.4% were females. The department of ophthalmology used mAbs most commonly (65.8%). Ranibizumab was the most used mAb in this department and overall. Conclusion: Out of the mAbs being used in the tertiary care center, only rituximab was part of the NLEM (India) essential drug list, and six more drugs were present in the WHO essential drug list. The advent of biosimilars is expected to bring costs down significantly for the patient and have better treatment outcomes.

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.

Background: Hematological malignancies, like other cancers, are on the rise. Their treatments have been revolutionized using biological molecules (biologics and biosimilars). These novel agents are used in the care of cancer patients and have significantly improved survival. While biosimilars are widely available, their use is still limited in some low- and middle-income countries, including Nigeria. Objectives: To determine the knowledge of healthcare workers (HCWs) at a tertiary hospital in Bauchi, Nigeria, before and after a structured training program on the use of biosimilars in hematological malignancies. Materials and Methods: Healthcare workers underwent a week-long training on biosimilars. Knowledge of pre- and post-training was ascertained using interviewer-administered questionnaires. Participant data was summarized as percentages in charts and tables and compared using the Z-test in Microsoft Excel 2016. P values ≤ 0.05 were considered significant. Results: One hundred and sixty one (161) participants attended the training, with females constituting 56.5%. Participants’ knowledge of cancer and hematological malignancies was significantly higher after training (82.1% vs. 61.5%; Z = 4.12, P

Gynecologic cancer is a critical concern in the field of women's health, and traditional treatment methods have demonstrated limited efficacy for certain advanced and recurrent gynecologic cancers. In recent years, antibody–drug conjugate (ADC) therapy, as an emerging targeted approach, has gained increasing attention as a research hotspot. This review aims to elucidate the structure and mechanism of ADC drugs and explore their application and clinical research progress in gynecologic cancers such as ovarian cancer, cervical cancer, and endometrial cancer. [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]

Objective: Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was to compare spinal radiographic progression in patients with radiographic axial SpA treated with secukinumab (interleukin‐17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ‐ADL]; tumor necrosis factor inhibitor). Methods: Biologic‐naive patients with active radiographic axial SpA, at high risk of radiographic progression (high‐sensitivity C‐reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs), were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ‐ADL (40 mg). The proportion of patients with no radiographic progression (change from baseline [CFB] in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤0.5) on secukinumab versus SDZ‐ADL at week 104 (primary endpoint), mean CFB‐mSASSS, proportion of patients with ≥1 syndesmophyte(s) at baseline with no new syndesmophyte(s), and safety were evaluated. Results: Overall, 859 patients (78.5% male, mSASSS 16.6, Bath Ankylosing Spondylitis Disease Activity Index 7.1, hsCRP 20.4 mg/L, and 73.0% with ≥1 syndesmophyte[s]) received secukinumab 150 mg (n = 287), secukinumab 300 mg (n = 286), or SDZ‐ADL (n = 286). At week 104, the proportion of patients with no radiographic progression was 66.1%, 66.9%, and 65.6% (P = not significant, both secukinumab doses) and mean CFB‐mSASSS was 0.54, 0.55, and 0.72 in secukinumab 150 mg, secukinumab 300 mg, and SDZ‐ADL arms, respectively. Overall, 56.9%, 53.8%, and 53.3% of patients on secukinumab 150 mg, secukinumab 300 mg, and SDZ‐ADL, respectively, with ≥1 syndesmophyte(s) at baseline did not develop new syndesmophyte(s) by week 104. There were no unexpected safety findings. Conclusion: Spinal radiographic progression over two years was low with no significant difference between secukinumab and SDZ‐ADL arms. The safety of both treatments was consistent with previous reports. [ABSTRACT FROM AUTHOR]

Objectives Adults with RA are being switched from etanercept originator to biosimilar in non-medical/cost-saving switching. This analysis aims to investigate outcomes in these patients, including (i) drug survival and (ii) disease activity at 6 months and 12 months, compared with those who remain on the originator. Methods Using BSRBR-RA, those who switched directly from etanercept originator to biosimilar were identified and matched to patients receiving the originator, based on gender, age, disease duration and originator start year. Drug survival was calculated; Cox-proportional hazard models assessed differences in drug persistence between those who switched vs remaining on originator. Change in DAS28 after 6 months and 12 months was compared between cohorts. Multiple imputation was used. Results A total of 1024 adults with RA switching from etanercept originator to biosimilar were included, with a matched cohort of patients remaining on the originator. Patients who switched onto a biosimilar product were no more likely to discontinue etanercept treatment vs those who remained on the originator; hazard ratio 1.06 (95%CI 0.89–1.26), with 65% of patients remaining on treatment at three years. Ninety-five (9%) patients switched back to the originator within the first year. After 6 months and 12 months, biosimilar patients were no more likely to have a worsening of DAS28 (>0.6 units) compared with those who remained on the originator. Conclusions This is the largest matched comparative effectiveness analysis showing patients switching from etanercept originator to biosimilar appearing to do just as well with regard to disease activity and drug persistence compared with those who remained on the originator. These data will be reassuring to clinicians and patients regarding non-medical switching. [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]

MSB11022 is a biosimilar of adalimumab that has been shown comparable bioequivalence, safety, tolerability, and immunogenicity profiles to the reference adalimumab in healthy volunteers or in patients with psoriasis or rheumatoid arthritis (RA). This is the first study conducted under clinical practice conditions evaluating the switch from reference adalimumab to MSB11022 in patients with RA. Retrospective and multicenter study with data from the medical records of patients with RA who switched from reference adalimumab or another biosimilar to MSB11022 and maintained this treatment for at least 6 months. Information registered comes from baseline visit, the moment of the switch, and the follow-up visits. Data from 86 patients were evaluated (median age 63.5 years, 75.6% female, 44.2% had erosive RA). Only 3.5% of the patients received biologic therapy prior to adalimumab. At baseline, median DAS28-CRP was 1.77 (80.2% in remission and 96.5% with low disease activity) and median CDAI was 4.00 (44.2% in remission and 90.7% with low disease activity). After a median follow-up of 8 months, median DAS28-CRP was 1.87 (86.0% in remission and 94.2% with low disease activity) and median CDAI was 4.00 (38.5% in remission and 95.3% with low disease activity). Only three patients experienced pain, swelling, and stinging at the injection site or a locally extensive hematoma in the area of administration. Adalimumab biosimilar MSB11022 maintained the efficacy benefits provided by previous adalimumab treatments with a safety profile in line with that already described for other biosimilars. [ABSTRACT FROM AUTHOR]

The possibilities of modern therapy for systemic sclerosis (SSc) remains limited, since most of the used drugs do not have a disease-modifying effect. This encourages the study of new approaches that potentially affect the fundamental pathological processes underlying the disease. One example is anti-B-cell therapy, in particular rituximab (RTX). Until now RTX does not have a registration for the treatment of SSc, but there is a large positive experience of its use, which is reflected in recent meta-analyses and clinical recommendations. Complicated and expensive methods for obtaining genetically engineered biological drugs (biologics) have contributed to the emergence of more accessible biosimilars, one of which is the RTX biosimilar, Acellbia (Biocad, Russian Federation). The "biosimilar" versions of RTX might reduce the cost of therapy and increase patients accessibility to this treatment option. The RTX biosimilar Acellbia (ACB) has received approval in Russian Federation in 2014 for all indications held by reference RTX (including rheumatoid arthritis and ANCA-associated vasculitis). [ABSTRACT FROM AUTHOR]

Building technological capabilities is influenced by different factors, notably policies. This paper explains the co-evolution of policies, i.e. policy tools, on the technological capabilities in Iran's biopharmaceutical sector from 1995 to 2022. By adopting a qualitative research method, we gathered primary data through thirty-nine semi-structured as well as secondary data from reports and statistics. This paper explains technological capabilities enhancement from operational capabilities to innovative capabilities based on our proposed framework, which includes six levels. While the lack of an efficient policy tools, until the mid-2000s, was decisive in the inertia of biopharmaceutical sector capabilities, a proactive policy tools in recent years led to considerable promising results in terms of manufacturing and exporting advanced biosimilar products. Our findings shed light on the role of government support in the acceleration and directionality of technological capabilities building. Achieving advanced levels of technological capabilities requires learning, international collaboration, and export-oriented policies. [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]

The Hatch-Waxman Act of 1984 ushered in a new era of affordable medicine, with 90% of all prescriptions today filled with generic drugs. Hatch-Waxman provided an expedited pathway for generic entry and mandated that the FDA publish up-to-date information on patent information related to non-biologic drugs. That publication is known as the Orange Book. Roughly twenty-five years later, the Biosimilars Act similarly aimed to facilitate the entry of less-expensive versions of biologics, which are more complex drugs made by living systems. Information related to biologics and biosimilars is published in what is known as the Purple Book. Biosimilars, however, have captured less of the biologic market and have reduced prices to a lesser extent than generic non-biologic drugs. To explore the biosimilars system’s shortcomings, this Article uses the case study of insulin drugs, which are popular biologics. Insulin offers a natural experiment, given that these drugs were originally listed in the Orange Book before moving to the Purple Book, in 2020. Comparing the intellectual property data available for insulin in both books reveals the surprising dearth of patent information disclosed in the Purple Book. In fact, despite taking inspiration from the Hatch-Waxman regime, the biosimilars system bears little resemblance to its muse. Indeed, the Purple Book is missing intellectual property data for most biologics. Without this information, biosimilar companies are forced to dance in the dark, running into legal barriers made by the brand’s patents. As a result, biosimilar hopefuls may be deterred or delayed from entering the market. The Article concludes with proposals to improve the regulatory pathway for licensing biosimilars and remedy the lack of patent transparency in the Purple Book. With these reforms, biosimilars are better poised to follow in the footsteps of generic drugs, increasing access to life-saving biologic medicines [ABSTRACT FROM AUTHOR]

A combination of improvements in patient survival, increasing treatment duration, and the development of more expensive agents has led to a doubling of per-capita spending on cancer medicines in Ireland (2008–2018). Despite this, access to new drugs is poor in comparison to other EU countries. We examine methods to optimise oncology drug spending to facilitate access to newer anticancer agents. Key targets for spending optimisation (biosimilar use, clinical trials and expanded access programs, waste reduction, avoidance of futile treatment, and altered drug scheduling) were identified through an exploratory analysis. A structured literature search was performed, with a focus on articles relevant to the Irish Healthcare system, supplemented by reports from statutory bodies. At the present time, EMA-approved agents are available once approved by the NCPE. Optimising drug costs occurs through guideline-based practice and biosimilar integration, the latter provides €80 million in cost savings annually. Access to novel therapies can occur via over 50 clinical trials and 28 currently available expanded access programmes. Additional strategies include reversion to weight-based immunotherapy dosing, potentially saving €400,000 per year in our centre alone, vial sharing, and optimisation of treatment schedules. A variety of techniques are being employed by oncologists to optimise costs and increase access to innovation for patients. Use of biosimilars, drug wastage, and prescribing at end of life should be audited as key performance indicators, which may lead to reflective practice on treatment planning. Such measures could further optimise oncology drug expenditure nationally facilitating approval of new agents. [ABSTRACT FROM AUTHOR]

Hidradenitis Suppurativa (HS), also known as Acne Inversa, is a chronic, recurrent inflammatory skin condition primarily affecting apocrine gland-bearing areas, such as the axilla and groin. Characterized by painful nodules, abscesses, and scarring, and has a profound psychological impact on patients. Current treatments aim to manage symptoms and prevent new lesions with a combination of non-pharmacological and pharmacological approaches. Emerging biosimilars, which replicate the efficacy and safety profiles of known biologics at a lower cost, offer new options for treating this debilitating cutaneous disorder. The review summarizes recent studies to explain the role of biosimilars in HS, emphasizing their potential to expand effective treatment options. [ABSTRACT FROM AUTHOR]