BIOCHEMISTRY, BIOMEDICINE & PHARMACEUTICS

Witztum  et al. recently published (New England Journal of Medicine, 2019) results from phase 3 clinical trials on efficacy and safety of antisense oligonucleotide Volanesoren in treatment of familial Chylomicronemia. Familial Chylomicronemia is a genetic disorder caused by mutation of enzyme lipoprotein lipase or associated proteins required for its function. Valonesoren inhibits the synthesis of Apoc-III, thereby decreasing the triglycerides level in patients with hypertriglyceridemia. Based on this clinical study, IONIS pharmaceutical obtained a positive opinion and conditional approval to market the product in the European Union region. ( Committee for Medicinal Products for Human Use- CHMP   Public Assessment Report   ) . The following are the excerpts and the result summary from the study: Witztum et al, 2019, NEJM Journal: New England Journal of Medicine Title: Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. Abstract BACKGROUND: F...

Meadows et al. recently published papers (Mol Ther Methods Clin Dev, 2019) that investigated the threshold of antibody titer levels that would limit the transduction efficiency of systematic rAAV9 gene delivery.  The early clinical trials have revealed a potential impact of preexisting antibodies against adeno associated virus in the efficacy of transgene expressions. This study attempts to characterize the correlation of transgene expression (NAGLU)  with preexisting antibody titers against AAV9.  The nonclinical nonhuman primate studies were conducted to evaluate the transduction efficiency after systemic delivery of rAAV9 at varying level of preexisting antibodies and define efficacy threshold if any. The following are the excerpts and the result summary from the study: Journal Title: Molecular Therapy: Methods & Clinical Development Title: Threshold for Pre-existing Antibody Levels Limiting Transduction Efficiency of Systemic rAAV9 Gene Delivery: Releva...

Long et al. & Majowicz et al. recently published papers (Mol Ther Methods Clin Dev, 2019) that reported potential impact of preexisting antibodies against adeno associated virus serotype 5 ( AAV5) in the efficacy of transgene expressions. These nonclinical nonhuman primate studies were conducted to evaluate the efficacy of the gene therapy at varying level of preexisting antibodies. Factor VIII and factor IX activity as measured as a pharmacodynamic marker of efficacy.  The Following are the excerpts and the result summary from the study: Journal: Molecular Therapy Methods & Clinical Development Title:  The Impact of Pre-existing Immunity on the Non-clinical Pharmacodynamics of AAV5-Based Gene Therapy Abstract Adeno-associated virus (AAV)-based vectors are widely used for gene therapy, but the effect of pre-existing antibodies resulting from exposure to wild-type AAV is unclear. In addition, other poorly defined plasma factors could inhibit AAV vector transd...

Bruce et al.  recently published a paper (PLOS Medicine, 2019) that provides a trend on the use of surrogate biomarkers to evaluate clinical benefits. The study primarily reviewed European Public Assessment Reports (EPARs) to identify the use of surrogate biomarkers for the primary endpoint.  The Following are the excerpts and the result summary from the study: Journal: PLOS Medicine Title: The use of validated and nonvalidated surrogate endpoints in two European Medicines Agency expedited approval pathways: A cross-sectional study of products authorized 2011–2018 Abstract BACKGROUND:  In situations of unmet medical need or in the interests of public health, expedited approval pathways, including conditional marketing authorization (CMA) and accelerated assessment (AA), speed up European Medicines Agency (EMA) marketing authorization recommendations for medicinal products. CMAs are based on incomplete benefit-risk assessment data and authorization remai...