A safety review of recent advancements in the treatment of psoriasis: analysis of clinical trial safety data

Introduction: The management of psoriasis can include oral medications and injectable biologics. Safety data of these various treatment options are important to consider when choosing the right treatment for the patient.

Areas covered: This review evaluates the safety of newer treatments approved for psoriasis, including interleukin-(IL)-17 inhibitors, IL-23/p19 inhibitors, ustekinumab, certolizumab pegol and apremilast, using phases III and IV clinical trial data.

Expert opinion: Even as treatment of psoriasis becomes safer, it is important to recognize both common and uncommon adverse effects of treatment. Common adverse effects are similar across treatment options, including upper respiratory infection and injection-site reaction. Serious adverse effects occur less frequently and specific to the psoriasis treatment option, such as inflammatory bowel disease and candida infections with IL-17 inhibitors, tuberculosis with certolizumab pegol, and psychiatric events with apremilast. While IL-23/p19 inhibitors may have a slightly better safety profile than other biologics, long-term data are limited. The conclusions that can be drawn from clinical trial safety data are limited given that many clinical trials are not large enough to detect rare safety events. Data from registries provide important complementary information on long-term safety but there are limitations including a lack of randomized assignment between drug treatments.     

A Randomized Phase I Study Comparing the Pharmacokinetics of HD201, a Trastuzumab Biosimilar,With European Union–sourced Herceptin

Purpose

This first-in-human study of HD201 was designed to evaluate the pharmacokinetic (PK) equivalence between this biosimilar candidate and trastuzumab sourced in the European Union (EU-trastuzumab)*.

Preventing shortages of biologic medicines

Shortages of small-molecule injectable drugs have captured the attention of patients, healthcare providers, regulators and policy makers in recent years. While these shortages have several causes, non-compliance with current good manufacturing practice and subsequent shutdowns of manufacturing facilities have played a central role. Sterile injectable drugs are particularly susceptible to manufacturing quality disruptions because of their sensitivity to contamination. Biologics are subject to the same fill-finish contamination risk as sterile injectables, but their active ingredients are also sensitive to subtle changes in the manufacturing process and to storage and handling of their final dosage forms. Originator biologics will lose market exclusivity in the years ahead as patents expire and as competitors develop biosimilar products. The availability of therapeutic alternatives may provide opportunities to reduce costs and increase patient access, but this should not come at the expense of critical investments in the manufacturing of these complex and sensitive products.     

Monoclonal antibodies: a morphing landscape for therapeutics

The concept of using antibodies as therapeutics to cure human diseases was postulated nearly 100 years ago by Paul Ehrlich and subsequently enabled by the discovery of hybridoma technology by Kohler and Milstein in 1975. While the use of monoclonal antibodies (mAbs) as drugs that can specifically target a disease‐associated antigen is compelling, it has taken a quarter century for these molecules to be adopted as bona fide therapeutic agents. Despite their slow pursuit in drug development during the pioneering years, it is now estimated that there are nearly 500 mAb‐based therapies in development. Major factors that have influenced the acceptance of monoclonal antibodies as therapeutics include their drug safety profiles, technological advancements for facilitating mAb discovery and development, and market success. Early on, it was demonstrated that antibodies could elicit clinical benefit by antagonizing a specific antigen without the common side effects that are prevalent with small chemical entities due to their nonspecific effects on homeostatic biochemical pathways. In addition, the significant technological advances that the biotechnology industry has established for developing and producing monoclonal antibodies at commercial scale in a more efficient and cost‐effective manner has broadly enabled their use as therapeutics. However, despite the beneficial pharmacologic advantages and technological advances, it has been the sheer market success that monoclonal antibody products have achieved over the past few years that has propelled their vast pursuit by the biopharmaceutical industry in light of their value‐creating potential. Here we provide an overview of the monoclonal antibody industry and discuss evolving technologies and strategies that are being pursued to overcome challenges in the changing marketplace. Drug Dev. Res. 67:781–789, 2006. © 2007 Wiley‐Liss, Inc.     

Current Japanese Regulatory Systems for Generics and Biosimilars

Currently, biosimilar products are being actively developed around the world. One reason for this is the expiry of patents of original biopharmaceutical products with an extremely large market share because the biosimilar companies need to avoid infringing patents. A representative example of this is biosimilar versions of monoclonal antibodies. In Japan, the Ministry of Health, Labour and Welfare is promoting the use of biosimilar products because the market share of such products is currently extremely low compared with that of generic products. The Pharmaceuticals and Medical Devices Agency is responsible for reviewing generic and biosimilar products in Japan. However, no comparison of review systems for generics and biosimilars in Japan has been published. A more detailed understanding of review systems is important for using generic and biosimilar products. This article presents the current Japanese review systems for generic and biosimilar products and also the future challenges to facilitate the better regulation of both types of product.     

A Systematic Literature Review of Gaps and Challenges in Value Assessment of Biosimilars: An ISPOR Special Interest Group Report

ObjectivesThis study aims to provide an overview of the gaps and challenges in the value assessment of biosimilars and to identify potential approaches to address them.MethodsA multidisciplinary, international team of biosimilar experts identified gaps and challenges. A systematic review was conducted of the peer-reviewed literature in PubMed, EMBASE, Web of Science Core Collection, EBSCOhost Business Source Complete; and of the gray literature. Preliminary results were presented at ISPOR conferences and this article benefited from 2 review rounds among ISPOR Biosimilar Special Interest Group members.ResultsGiven that a biosimilar is highly similar to its reference biologic, health technology assessment agencies should accept the comparability exercise approved by regulatory authorities and, thus, conduct a price comparison when biosimilar reimbursement is requested for the same indication as the reference biologic. If the reference biologic is not reimbursed or is not the standard of care, a full economic evaluation of the biosimilar versus a relevant comparator needs to be conducted. To date, little consideration has been given to specific challenges, such as how biosimilar value assessment can account for the nocebo effect, potential differences between biologic-naive and biologic-experienced patients, the availability of intravenous and subcutaneous administration forms or different administration devices for the same active compound, value-added services, and the contribution of biosimilars for generating health gain at the population level.ConclusionsThere is a need to gather further insights in the methodology of value assessment for biosimilars, and health technology assessment agencies need to develop more elaborate guidance on biosimilar value assessment in specific circumstances.