Biomarkers: Opportunities and Challenges for Drug Development in the Current Regulatory Landscape.

Biomarkers are widely used at every stage of drug discovery and development. Utilisation of biomarkers has a potential to make drug discovery, development and approval processes more efficient. An overview of the current global regulatory landscape is presented in this article with particular emphasis on the validation and qualification of biomarkers, as well as legal framework for companion diagnostics.

19th Annual Meeting of the Safety Pharmacology Society: regulatory and safety perspectives for advanced therapy medicinal products (cellular and gene therapy products).

This report summarizes and discusses talks delivered at an educational course offered during the 2019 Annual Meeting of the Safety Pharmacology Society on advanced therapy medicinal products (ATMPs) and cell gene therapeutic products (CGTPs). ATMPs and CGTPs comprise gene and cell therapy medicinal products, tissue-engineered products, or the incorporation of one of these products into a medical device. Cited examples of ATMPs are autologous CD34 cells encoding for the β-globin gene, CAR (chimeric antigen receptor)-T cell immunotherapy medicines, genome editing products, and engineered heart muscle patches constructed from induced human pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for remuscularization of the failing human heart.

From fiction to science: clinical potentials and regulatory considerations of gene editing.

Gene editing technologies such as CRISPR/Cas9 have emerged as an attractive tool not only for scientific research but also for the development of medicinal products. Their ability to induce precise double strand breaks into DNA enables targeted modifications of the genome including selective knockout of genes, correction of mutations or precise insertion of new genetic material into specific loci. Gene editing-based therapies hold a great potential for the treatment of numerous diseases and the first products are already being tested in clinical trials.

Approval of First CAR-Ts: Have we Solved all Hurdles for ATMPs?

T cells are known as the most potent killer cells of the immune system, designed by nature to prevent unwanted challenges. The first class of therapeutic products harnessing the power of T cells for target-specific treatment of oncological diseases was bispecific antibodies. The first T-cell engaging bispecific antibodies that obtained approval were catumaxomab and blinatumomab.

Expediting Drug Development: FDA's New Regenerative Medicine Advanced Therapy Designation.

In March 2017, the US FDA introduced the new Regenerative Medicine Advanced Therapy (RMAT) designation thus recognizing the enormous potential of these medicines and the need for efficient regulatory tools to accelerate their development and their commercial availability. The development of regenerative medicines is very challenging because of their complex and unique nature, especially to the rather unexperienced small- and medium-sized developing enterprises. With the new RMAT designation, FDA aims at providing intensive support to companies developing cell- and tissue-based therapies, tissue-engineering products, and combination treatments.

The role of relative lymphocyte count as a biomarker for the effect of catumaxomab on survival in malignant ascites patients: results from a phase II/III study.

Purpose: We report the role of relative lymphocyte count (RLC) as a potential biomarker with prognostic impact for catumaxomab efficacy and overall survival (OS) based on a post hoc analysis of the pivotal phase II/III study of intraperitoneal catumaxomab treatment of malignant ascites.

Experimental Design: The impact of treatment and RLC on OS was evaluated using multivariate Cox models. Kaplan-Meier and log-rank tests were used for group comparisons.

Transient lymphocyte decrease due to adhesion and migration following catumaxomab (anti-EpCAM x anti-CD3) treatment in vivo.

Introduction: In patients, a transient decrease in peripheral blood lymphocyte counts was observed following intraperitoneal administration of the trifunctional monoclonal antibody catumaxomab (anti-human EpCAM x anti-human CD3). The aim of this study was to clarify the observed effect in a preclinical mouse model and to analyse the related mechanism of action in vitro.

Materials And Methods: A related antibody, BiLu (antihuman EpCAM x anti-mouse CD3), was administered to mice and blood leukocytes were analysed.

Novel monoclonal antibodies for cancer treatment: the trifunctional antibody catumaxomab (removab).

THE TRIFUNCTIONAL ANTIBODY (TRAB) CATUMAXOMAB IS CHARACTERIZED BY A UNIQUE ABILITY TO BIND THREE DIFFERENT CELL TYPES: tumor cells; T-cells; and accessory cells. It binds to epithelial cell adhesion molecule (EpCAM) on tumor cells, the CD3 antigen on T-cells, and to type I, IIa, and III Fcγ receptors (FcγRs) on accessory cells (e.g.

Humoral response to catumaxomab correlates with clinical outcome: results of the pivotal phase II/III study in patients with malignant ascites.

The trifunctional antibody catumaxomab is a targeted immunotherapy for the intraperitoneal treatment of malignant ascites. In a Phase II/III trial in cancer patients (n = 258) with malignant ascites, catumaxomab showed a clear clinical benefit vs. paracentesis and had an acceptable safety profile.

Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy.

Catumaxomab is a trifunctional antibody (trAb) characterized by its unique ability to bind three different cell types: tumor cells, T-cells, and accessory cells. It has two different antigen-binding specificities: one for epithelial cell adhesion molecule (EpCAM) on tumor cells and one for the CD3 antigen on T-cells. Catumaxomab also binds to type I, IIa, and III Fcγ receptors (FcγR) on accessory cells, e.

Catumaxomab: clinical development and future directions.

Catumaxomab, a monoclonal bispecific trifunctional antibody, was approved in the European Union in April 2009 for the intraperitoneal treatment of patients with malignant ascites. The marketing authorization holder Fresenius Biotech GmbH developed catumaxomab (Removab(®)) together with its partner TRION Pharma GmbH, Germany. It is the first substance worldwide with a regulatory label for the treatment of malignant ascites due to epithelial carcinomas.