In this draft guidance, the FDA emphasizes that potency assays and their corresponding acceptance criteria should be designed to make meaningful contributions to potency assurance by reducing risks to product potency. They provide illustrative examples of approaches to potency assay development that are...
INTRODUCTION: Immunogenicity refers to the ability of a substance, such as a therapeutic drug, to elicit an immune response. While beneficial in vaccine development, undesirable immunogenicity can compromise the safety and efficacy of therapeutic proteins by inducing anti-drug antibodies (ADAs). These ADAs can reduce drug bioavailability and alter pharmacokinetics, necessitating comprehensive immunogenicity risk assessments starting [...]
INTRODUCTION: Immunogenicity, the unwanted immune response triggered by therapeutic antibodies, poses significant challenges in biotherapeutic development. This response can lead to the production of anti-drug antibodies, potentially compromising the efficacy and safety of treatments. The internalization of therapeutic antibodies into dendritic cells (DCs) is a critical factor influencing immunogenicity. Using monoclonal antibodies, with differences in [...]
BACKGROUND: The success of anti-tumor necrosis factor (TNF) drug strategies in the treatment of inflammatory bowel disease (IBD) is altered by the development of anti-drug antibodies that reduce their efficacy. Studies have shown that the HLA-DQA1 small star, filled05 allele increases the risk of immunogenicity to anti-TNF drugs approximately twofold. OBJECTIVE: Analyze whether the presence [...]
BACKGROUND: Development of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) to monoclonal antibodies may adversely impact pharmacokinetics, efficacy, and/or safety. OBJECTIVE: To describe incidence, titer, and persistence of dupilumab ADAs and NAbs, and their effects on pharmacokinetics, efficacy, and safety in patients with atopic dermatitis (AD). METHODS: This analysis included seven phase 3 randomized, placebo-controlled [...]
INTRODUCTION: Immunogenicity continues to be a challenge for development and clinical utility of monoclonal antibodies, and there are gaps in our current ability to prevent anti-drug antibody development in a safe and antigen-specific manner. METHODS: To mitigate immunogenicity of monoclonal antibodies administered subcutaneously, O-phospho-L-serine (OPLS)-the head group of the tolerance-inducing phospholipid, phosphatidylserine-was investigated as an [...]
The clinical immunogenicity assessment for complex multidomain biological drugs is challenging due to multiple factors that must be taken into consideration. Here, we describe a strategy to overcome multiple bioanalytical challenges in order to assess anti-drug antibodies (ADA) for a novel and unique chemically modified protein therapeutic. A risk-centered approach was adopted to evaluate the [...]
The immunogenicity of cemiplimab, a fully human immunoglobulin G4 monoclonal antibody directed against programmed cell death 1, was assessed in patients across multiple tumor types. The development of antidrug antibodies (ADAs) against cemiplimab was monitored using a validated bridging immunoassay. To identify ADA-positive samples in the assay, statistically determined cut points were established by analyzing [...]
In a groundbreaking development, the U.S. Food and Drug Administration (FDA) has approved two revolutionary treatments, Casgevy and Lyfgenia, marking a significant milestone in the field of gene therapy. These therapies represent the first-ever cell-based gene treatments for sickle cell disease (SCD) in patients...
IFNbeta (recombinant interferon Beta) has been widely used for the treatment of Multiple sclerosis for the last four decades. Despite the human origin of the IFNbeta sequence, IFNbeta is immunogenic, and unwanted immune responses in IFNbeta-treated patients may compromise its efficacy and safety in the clinic. In this study, we applied the DeFT (De-immunization of [...]
