Anti-TNF biosimilars in Crohn’s Disease: a patient-centric interdisciplinary approach

ABSTRACT

Introduction: The purpose of this review is to highlight the role of biosimilars in early treatment in IBD and introduce ways to facilitate a patient-centric switching process through multidisciplinary approach.

Areas covered: We summarize existing scientific literature related to the role of biosimilars in inflammatory bowel disease in terms of early treatment and cost-saving and implementing switching process.

Expert opinion: Use of anti-TNF biosimilars in patients has the potential for large drug-acquisition cost-saving, which can be reinvested into early treatment. Managed switched programs for adalimumab can add further benefits in the future.     

Demonstrating Value for Biosimilars: A Conceptual Framework

Background

The value proposition for biosimilars can be characterized as a concept that moves beyond the argument of cost reduction relative to the innovator biologic drug and into a framework that incorporates the diverse needs of key healthcare stakeholders during the transition from clinical development to commercialization in the marketplace.

Objectives

To identify factors that facilitate and inhibit the development, commercialization, and adoption of biosimilars, and to recommend modifications in program design that are likely to support the demonstration of the value of biosimilars for payers, providers, and patients.

Methods

The primary data sources for this article include surveys conducted by Boston Healthcare Associates with payers and clinicians in the United States and the European Union 5 markets and blinded international protocol feasibility assessments completed by Worldwide Clinical Trials. Survey methodology used either convenience or purposeful sampling as appropriate, with participants extracted from diverse audiences, representative of those who generate or evaluate clinical data shaping the economic exchange and preferential status influencing physician adoption and patient access to biosimilars. Patient characteristics and psychosocial issues influencing patients'' perception of small-molecule generics were extracted from the available literature to inform exploratory hypotheses, given the relative absence of such information for biosimilars.

Discussion

This article reviews the current evidence and summarizes results of surveys conducted with payers, providers, and drug investigation sites in the United States. Based on a review of published literature, as well as these survey results, conflicting and convergent demands exist for gathering data related to biosimilars. The motivations and data needs for these new agents are diverse, requiring adjudication of regulatory, economic, and clinical incentives beginning at program inception and extending through commercialization of the final biosimilar agent.

Conclusions

The development and commercialization of biosimilars represent an international activity that can encounter unanticipated challenges, as well as opportunities to achieve clinical and commercial success. Evolving regulatory guidance mapped in relation to payer, physician, and patient sentiments may inform the biosimilar development program designs, implementation, and positioning of the new drug.     

Safety and efficacy of granulocyte colony-stimulating factor biosimilars in engraftment after autologous stem cell transplantation for haematological malignancies: a 4-year,single institute experience with different conditioning regimens

BackgroundFilgrastim biosimilars have recently been introduced into clinical practice. To date biosimilars have demonstrated comparable efficacy and safety as the originator in chemotherapy-induced neutropenia. Published experience in engraftment after autologous stem cell transplantation (ASCT) is limited and concerns relatively few patients.ResultsNeutrophil counts recovered in 55 patients. The median number of filgrastim biosimilar vials injected was seven per patient. The median time to neutrophil and platelet recovery was 10 and 12 days, respectively. Twenty-six patients had febrile neutropenia, in half of whom the agent involved was identified. In the cost analysis, the use of Tevagrastim^® and Zarzio^® was associated with cost reductions of 56% and of 86%, respectively.DiscussionDespite differences in CD34+ cell counts and time of starting filgrastim, our results in terms of time to engraftment and median number of vials injected are similar to published data. Comparing our results by single conditioning regimen to recent literature data, the time to engraftment and duration of hospitalisation were equivalent. Significant differences were observed in the incidence of febrile neutropenia, perhaps due to different preventive and prophylactic protocols for infections. Although prospective studies should be performed to confirm our results, filgrastim biosimilars were found to be effective and safe in engraftment after ASCT.     

Anti-drug antibodies in Colombian patients with rheumatoid arthritis treated with Enbrel vs Etanar – Preliminary report

The present study was undertaken to detect antibodies against etanercept (ETN) in a group of Colombian patients with rheumatoid arthritis (RA) and being treated with Enbrel^® vs. Etanar^®. From these patients with RA, clinical and laboratory data were collected and serum taken for anti-drug antibody (ADAb) analysis. Samples from 32 patients (16 who had been treated with Enbrel^® and 16 with Etanar^®) were analyzed. Positive sera for ADAb were found in six of the 32 subjects (18.7%); five (31.2%) in the Enbrel^® group and one (6.25%) in the Etanar^® group. Patients under treatment with Enbrel^® registered a longer disease duration than patients being treated with Etanar^® (15.4 years vs. 10.98 years, p?=?0.175) as well as a longer average treatment with the drug (45.7 vs. 23.9 months, p?=?0.052). The percentage of patients with disease activity defined as a disease activity score by C-reactive protein (DAS28-CRP) scores ≥2.3 was higher in those patients with positive sera in the enzyme-linked immunosorbent assay (ELISA) (66.7%) than in those with negative sera (34.6%). A logistic regression test revealed that the higher the DAS28-CRP value, the higher the ELISA absorbance value. The results showed evidence of greater frequency of ADAb in patients treated with ETN than has been reported to date. Greater disease activity was seen in those patients in whose serum ADAb had been detected. Significant differences were found between the positive ELISA for the group of patients treated with Enbrel^® compared to those treated with Etanar^®. Some of the factors that could explain this difference are the length of the treatment time with the drug, the commercial ELISA kit used to detect ADAb, or the immunogenicity itself of each product.     

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

ABSTRACT

Background and objective: Biosimilars are approved biologics that are comparable to an originator product with respect to quality, safety and efficacy. Herein, the authors describe the functional and non-clinical studies designed to determine the biosimilarity of GP2015 and originator etanercept (Enbrel®).

Methods: The development of an Enbrel biosimilar (GP2015) involved extensive characterization of the originator. A step-wise target-directed and iterative technical development program involving state-of-the-art functional characterization studies and non-clinical evaluations (pharmacokinetics, pharmacodynamics and safety/toxicology) was applied with the aim of confirming that GP2015 is comparable to originator (Enbrel) at the non-clinical level.

Results: In in vitro tests, GP2015 and Enbrel had comparable binding affinities to TNF-α, C1q complement and a complete panel of Fc-Receptors. Comprehensive functional characterization testing confirmed the comparability of GP2015 with Enbrel in terms of its ability to bind to and neutralize TNF-α, which reflects the primary mechanism of action of etanercept. Non-clinical data confirmed that the proposed biosimilar to Enbrel, GP2015, is comparable with regards to its pharmacokinetic properties and pharmacodynamic activity, and efficacy as well as safety/toxicity.

Conclusion: The proposed Enbrel biosimilar, GP2015, was shown to be comparable to its originator product in studies designed to confirm biosimilarity.     

Biosimilars: the paradox of sharing the same pharmacological action without full chemical identity

The use of biotech medicines is increasing, with consequent mounting expenses for National Health Systems (NHSs). Biosimilars should be considered an opportunity to improve access to care. On the other side, the general public might suspect to receive low-quality medicines to save money. Actually, no drugs with a lesser degree of pharmaceutical quality with respect to existing alternatives can be authorized on the ground of a lower price. Biosimilars can be authorized only if their quality is of the same level as that of the originator. There is no chemical identity between biosimilars and the originators: any differences in quality attributes must be justified and shown not to impact on the safety and efficacy of the biosimilar by scientific investigations including pre-approval nonclinical and/or clinical studies. The biosimilar safety profile may be different from the originator or change over time for the same product. Hence caveats limiting the widespread use of biosimilars yet exist and should be solved by education on the main biological issues of biotech medicines, and on continuous update of the rules set up by the Regulatory Authorities to assess biosimilarity and to monitor post-approval safety.     

Mindful Prescribing: Drug Development,Drug Selection,and Advanced Nursing Practice

There are multiple influences impacting new drug development and use. Aside from filling therapeutic gaps, prescribing is influenced by economic and social factors about which the nurse practitioner (NP) needs awareness. For instance, over half of newly approved drugs have been granted orphan drug status. Although these drugs have been useful in the treatment of rare diseases, this designation affects the use and cost of drugs that the NP may prescribe. Recognition of the multiple, complex factors impacting how a drug gets to market may enhance the NP’s decision making in the selection of agents and autonomy in advanced practice.