2
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Biosimilars of monoclonal antibodies in inflammatory diseases and cancer: current situation, challenges, and opportunities Translated title: Biosimilares de anticuerpos monoclonales en enfermedades inflamatorias y cáncer: situación actual, retos y oportunidades

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Abstract The approval pathway for biosimilars of monoclonal antibodies in the European Union is aimed at ruling out the presence of significant differences with the original biological in quality attributes, efficacy, immunogenicity and safety. It also provides the rationale for extrapolating the evidence obtained with a biosimilar in at least one indication to the rest of the approved indications of its original biological, thus simplifying the development programme of biosimilars. Biosimilars of monoclonal antibodies available in the European Union for the treatment of inflammatory diseases and cancer have fulfilled all the requirements for approval, and many of them have additional evidence available. Moreover, real world data confirms the safety and efficacy of these drugs in the indications they are being used for. In Spain, many scientific societies endorse the regulatory pathway of biosimilars and acknowledge their role in the efficiency of the healthcare system. Even so, some barriers remain that limit their use. The implementation of different measures at the patient, prescriber, institutional, and national levels might increase the penetration of biosimilars, freeing up resources that may be invested in other therapies and, potentially, boost innovation.

          Translated abstract

          Resumen El proceso de aprobación de los biosimilares de anticuerpos monoclonales en la Unión Europea está dirigido a descartar la presencia de diferencias significativas con el biológico original en los atributos de calidad, eficacia, inmunogenicidad y seguridad. Proporciona además la justificación para extrapolar la evidencia obtenida con un biosimilar en al menos una indicación al resto de indicaciones aprobadas para su biológico original, simplificando el programa de desarrollo de los biosimilares. Los biosimilares de anticuerpos monoclonales disponibles en la Unión Europea para el tratamiento de enfermedades inflamatorias y del cáncer han cumplido todos los requerimientos establecidos para la aprobación, y en muchos casos disponen de evidencia adicional. Además, los datos de uso en la vida real están confirmando la seguridad y eficacia de estos fármacos en las distintas patologías en las que se están utilizando. En España, varias sociedades médicas avalan el proceso regulatorio de los biosimilares y reconocen su papel en la eficiencia del sistema sanitario. No obstante, todavía existen algunas barreras que limitan su uso. La aplicación de diferentes medidas a nivel de paciente, prescriptor, institucional y nacional podría aumentar la penetración de los biosimilares, liberando recursos que podrían invertirse en otras terapias y, potencialmente, favorecer la innovación.

          Related collections

          Most cited references18

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4

          Objectives SB4 (Benepali, Brenzys) is a biosimilar of reference etanercept (ETN). In a randomised, double-blind, 52-week study, SB4 demonstrated comparable efficacy and safety to ETN in patients with rheumatoid arthritis (RA). The open-label extension period evaluated long-term efficacy, safety and immunogenicity when continuing SB4 versus switching from ETN to SB4. Methods In the randomised, double-blind phase, patients received weekly subcutaneous administration of 50 mg SB4 or ETN with background methotrexate for up to 52 weeks. Patients in the Czech Republic and Poland who completed the 52-week visit were enrolled in the open-label extension period and received SB4 for 48 additional weeks. Efficacy, safety and immunogenicity were assessed up to week 100. Results Of 245 patients entering the extension period, 126 continued to receive SB4 (SB4/SB4) and 119 switched to SB4 (ETN/SB4). American College of Rheumatology (ACR) response rates were sustained and comparable between SB4/SB4 and ETN/SB4 with ACR20 response rates at week 100 of 77.9% and 79.1%, respectively. Other efficacy results, including radiographic progression, were also comparable between the groups. After week 52, rates of treatment-emergent adverse events were 47.6% (SB4/SB4) and 48.7% (ETN/SB4); one patient/group developed non-neutralising antidrug antibodies. No cases of active tuberculosis or injection-site reactions were reported during the extension period. One patient (SB4/SB4) died of hepatic cancer. Conclusions SB4 was effective and well tolerated over 2 years in patients with RA. Efficacy, safety and immunogenicity were comparable between the SB4/SB4 and ETN/SB4 groups, showing no risk associated with switching patients from ETN to SB4. Trial registration number NCT01895309; 2012-005026-30
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Developing the Totality of Evidence for Biosimilars: Regulatory Considerations and Building Confidence for the Healthcare Community

            Biosimilars are highly similar versions of approved branded biologics. Unlike generics, they are not exact replicas of reference products. Minor differences between biosimilars and reference products in some aspects are expected; likewise, biosimilar products will differ from each other. The objective of this review is to discuss the challenges associated with the development and approval of biosimilar products that are unique because of their complex structure and specialized manufacturing processes, which can impact not only efficacy but also immunogenicity and safety. Regulatory guidelines recommend a totality-of-evidence approach focused on stepwise development that involves demonstration of structural similarity and functional equivalence. Structural and functional characteristics of the proposed biosimilar are compared with the reference product; similarity of these functions forms the foundation of the biosimilar development program, including potential animal studies, a human pharmacokinetics/pharmacodynamics equivalence study, and a clinical study to confirm similar efficacy, safety, and immunogenicity. The clinical study should be performed in a sensitive population using appropriate endpoints to allow detection of any clinically meaningful differences between the biosimilar and the reference product if such differences exist. In conclusion, development of biosimilars is focused on the minimization of potential differences between the proposed biosimilar and reference product and the establishment of a robust manufacturing process to consistently produce a high-quality biosimilar product.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              An open-label extension study to demonstrate long-term safety and efficacy of ABP 501 in patients with rheumatoid arthritis

              Background ABP 501 was evaluated in a phase 3 single-arm, open-label extension (OLE) study to collect additional safety and efficacy data in patients with rheumatoid arthritis (RA). Methods Subjects completing the final visit in the parent phase 3 randomized, double-blind, controlled equivalence study comparing the efficacy and safety of the biosimilar ABP 501 with adalimumab reference product (RP) were enrolled in this open-label extension (OLE) study. All subjects received 40 mg ABP 501 every other week for 68 weeks. Key safety endpoints included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and anti-drug antibody (ADA) incidences. Efficacy endpoints included ACR20 (at least 20% improvement in American College of Rheumatology core set measurements from baseline) and Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP) change from baseline. Results Among 466/467 patients treated with ABP 501, 229 transitioned from the ABP 501 arm of the parent study (ABP 501/ABP 501) and 237 from the adalimumab RP arm (RP/ABP 501); 412/467 (88.2%) patients completed the study. The overall TEAE incidence was 63.7% (297/466); grade ≥ 3 TEAE incidence was 9.0% (42/466). The incidence of TEAEs leading to discontinuation of investigational product was 3.6% (17/466). The SAE incidence was 9.9% (46/466). Overall, 18.2% (85/466) of subjects developed binding ADAs and 6.9% (32/466) developed neutralizing ADAs in the OLE study. The ACR20 response rate was 73.3% (340/464 subjects) at OLE baseline, and 78.8% (327/415 subjects) at week 70 of the OLE study. The overall mean DAS28-CRP change from the parent study baseline was − 2.25 at the OLE study baseline (n = 440), − 2.36 at week 4 (n = 463), − 2.41 at week 24 (n = 450), − 2.55 at week 48 (n = 433), and − 2.60 at week 70 (n = 412). Efficacy was maintained throughout the study. Conclusions Efficacy previously demonstrated in the parent study was maintained in this OLE study with no new safety findings. Long-term safety, immunogenicity, and efficacy were similar in the ABP 501/ABP 501 and RP/ABP 501 groups. The single switch from RP to ABP 501 did not impact immunogenicity. Trial registration ClinicalTrial.gov, NCT02114931
                Bookmark

                Author and article information

                Journal
                fh
                Farmacia Hospitalaria
                Farm Hosp.
                Grupo Aula Médica (Toledo, Toledo, Spain )
                1130-6343
                2171-8695
                June 2020
                : 44
                : 3
                : 100-108
                Affiliations
                [1] Seville orgnameHospital Universitario Virgen Macarena orgdiv1Pharmacy department Spain
                [2] Madrid orgnameHospital Clínico Universitario San Carlos orgdiv1Pharmacy department Spain
                [3] Barcelona orgnameAmgen S.A Spain
                Article
                S1130-63432020000300006 S1130-6343(20)04400300006
                10.7399/fh.11280
                32452309
                46b0af8e-c9f5-4611-b818-b97b3f311d66

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 20 May 2019
                : 28 February 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 44, Pages: 9
                Product

                SciELO Spain

                Categories
                Review

                Extrapolación,Eficiencia,Efficiency,Intercambiabilidad,España,Cancer,Biosimilares,Spain,Inflammatory diseases,Nocebo,Extrapolation,Interchangeability,Biosimilars,Cáncer,Enfermedades inflamatorias

                Comments

                Comment on this article