Evaluation of a biosimilar recombinant alpha epoetin in the management of anemia in hemodialysis patients

Background: The efficacy of human recombinant erythropoietins (rHuEPOs) in the treatment of anemia with different etiologies is proven. Development of biosimilar rHuEPO products with lower cost and wider availability is important for the care of anemic patients. Objective: The aim of the present study was to determine the bioequivalence and safety of a biosimilar rHuEPO (Pastopoitin^®) and compare it with the innovator product Eprex^®, as a standard rHuEPO. Methods: One hundred and seven anemic patients on stable hemodialysis were recruited to this randomized double-blind comparative trial and assigned to either subcutaneous Pastopoitin (n = 50) or Eprex (n = 57). Each study group received rHuEPO at a dose of 80–120 IU/kg/week in 2–3 divided doses for a period of 3 months. Hematologic parameters including Hemoglobin, hematocrit, RBC, EBC, platelet, MCV, MCH and MCHC were checked every 2 weeks. Blood iron, ferritin, TIBC, creatinine, BUN and electrolytes (Na, K, Ca and P) were evaluated monthly over the 3 months. Results: A significant increase in hemoglobin, hematocrit and RBC was observed by the end of study in both Pastopoitin and Eprex groups (p < 0.001). However, these factors were not significantly different between the groups, neither at baseline nor at the end of study (p > 0.05). Likewise, the groups were comparable regarding MCV, MCH, MCHC, iron, ferritin, TIBC, creatinine, BUN and electrolytes at baseline as well as at the end of trial. Adverse events were not serious and occurred with the same frequency in the study groups. Conclusion: Pastopoitin showed comparable efficacy and safety profile with Eprex in anemic patients on hemodialysis. Hence, Pastopoitin may be considered as a rHuEPO with a lower cost and wider availability compared with the innovator product Eprex.     

Biosimilar DMARD in rheumatology: A general perspective with focus on India

Biologic disease modifying anti-rheumatic drugs (DMARD) have revolutionized the management of several rheumatic disorders, especially those with autoimmune inflammatory etiology. A decade of experience has further endorsed their efficacy and unraveled safety issues. Treat to target remission is the current mantra. Infections remain the single most important complication. However, the access to biologics has been severely restricted by their exorbitant cost. Several biologics will lose their patent in the imminent future. An exact replica of a protein molecule is difficult if not impossible. Molecules seemingly similar to biologics called biosimilars or ‘follow on biologics’ are likely to flood the markets world wide at a challenging and affordable price. However, the acceptability of biosimilars will be driven by several contentious issues connected with manufacture, standardization, extent of validation (compared to source innovator biologic), interchangeability (with biologic), regulatory issues, and other patient centric socioeconomic issues. India is likely to provide a fertile field for biosimilar drugs and patients stand to gain from an expanded access and newer treatment paradigms. The fierce competition between several pharmaceutical companies (Indian and multinationals) to gain supremacy will fuel better affordability, equity and access to medicine while upholding the science of quality drugs. The stage is now set for this next big revolution in therapeutics.     

Biosimilarity assessment of biosimilar therapeutic monoclonal antibodies

The concept of biosimilar was established in the early 2000s in EU. Currently, the regulatory framework for biosimilar has also been established in the US, Japan, and other countries. As of 2018, biosimilars for infliximab, adalimumab, rituximab, trastuzumab, and bevacizumab have been approved. During the development of a biosimilar, product quality should be evaluated and compared with those of the reference product extensively. Among the quality attributes of therapeutic antibodies, FcRn binding and related structures are well known to affect the pharmacokinetic profile of the product. Other quality attributes such as antigen binding, glycan structure, and isoelectric point are considered to have a potential impact on the pharmacokinetic profile of the product. Based on the high similarity of the quality attributes of the biosimilar to those of its reference product, comparative non-clinical and clinical studies are conducted. Comparable pharmacokinetic profile of the biosimilar and the reference product is important for biosimilar evaluation. In this review, the basic concept of biosimilar development as well as pharmacokinetic data obtained via non-clinical and clinical studies of biosimilar therapeutic antibody is introduced, and future perspective is discussed.     

The biosimilar pathway in the USA: An analysis of the innovator company and biosimilar company perspectives and beyond

In order to improve access to costly biological treatments, a biosimilar pathway in the United States of America (USA) was enacted under the Biologics Price Competition and Innovation Act (BPCI Act) of 2009. The aim of the present study was to investigate how the health policy, the establishment of the biosimilar pathway, influenced related companies by studying their respective perspectives and strategies revealed in literatures and publicly available resources. Perspectives of companies reveal the points of concern for the biosimilar pathway, such as data requirements, patents, interchangeability, naming, and exclusivity. Innovator companies may utilize expedited programs for serious conditions, enhance patent protection, launch programs for life-cycle extension, and develop biosimilars as well. The biosimilar companies overcoming technical barriers might need to gather convincing evidence to facilitate market penetration as well as to distinguish their products from those of other biosimilar competitors. More challenges are expected for innovator companies if international harmonization takes place, which might be worth further investigation.     

Extrapolation: Experience gained from original biologics

Biologicals undergo modifications throughout their commercial lifecycle. Major changes can unintentionally magnify their inherent physicochemical variability. Although trials comparing the pre- and the post-change versions have been requested occasionally, analytical comparison is the most sensitive approach to anticipating clinical equivalence. Therefore, it may be concluded, by means of ‘extrapolation’, that non-identical versions of a given biologic will behave equally in all indications. Despite the lessons learned with original biologics, there are still controversies around the approval of biosimilars through extrapolation. Here, a comprehensive analysis of scattered information allows for an account of cases of original biologic versions approved in some indications with no patient trials involved. Healthcare professionals can be reassured that inasmuch as extrapolation has proven valid for new versions of original biologics, the same holds for biosimilars.     

Rituximab biosimilars for lymphoma in Europe

ABSTRACT

Introduction: The approval of rituximab, a monoclonal antibody targeting CD20, revolutionized the treatment of B-cell non-Hodgkin lymphomas and became an undisputed standard of care. However, as with all biologic medicines, the complex development and manufacturing process for rituximab have meant that the medicine attracts high treatment costs. Approved rituximab biosimilars have been comprehensively demonstrated to match the reference medicine. With the potential to increase access to biologic therapy, they have a key role in helping to improve patient outcomes in lymphoma care.

Areas covered: In this review, we discuss the role of rituximab in the treatment of lymphoma. We explore development and regulatory requirements for biosimilar development and the potential impact of these medicines on access and sustainability. Focusing on biosimilars of rituximab, we examine in detail the evidence for biosimilarity for the two rituximab biosimilars that are approved in Europe and provide an overview of rituximab biosimilars currently in development.

Expert opinion: We foresee a wider uptake of biosimilar medicines for lymphoma treatment over the next 5 years. The associated cost savings should be invested in broadening patient access to biological therapies, enabling wider use of more expensive treatment strategies and driving innovation in cancer care.     

Is there a reason for concern or is it just hype? – A systematic literature review of the clinical consequences of switching from originator biologics to biosimilars

Introduction: While prescribing biosimilars to patients naive to a biologic treatment is a well-accepted practice, switching clinically stable patients from an originator to a biosimilar is an issue for clinicians. Well-designed clinical trials and real-world data which study the consequences of switching from an originator biologic treatment to its biosimilar alternative are limited, especially for monoclonal antibodies.

Areas covered: A systematic literature review was conducted on PubMed to identify evidence of the consequences of switching from original biologics to biosimilars. References of included papers were also scrutinized. After a title-, abstract- and full text screening, out of the 153 original hits and 77 additional ones from screening the references, 58 papers (12 empirical papers, 5 systematic reviews and 41 non-empirical papers) were included.

Expert opinion: Preventing patients on biologic medicines from switching to biosimilars due to anticipated risks seems to be disproportional compared to the expected cost savings and/or improved patient access. Indeed, it is the opinion of the authors that the concern of switching to biosimilars is overhyped.