Biomarker-Driven Developments in the Context of the New Regulatory Framework for Companion Diagnostics in the European Union.

The new In Vitro Diagnostic Regulation (EU) 2017/746 (IVDR) introduces important changes in the EU legal framework for companion diagnostics (CDx), including a new risk-based classification system for in vitro diagnostic tests (IVDs), a first legal definition for CDx and enhanced involvement of notified bodies in the conformity assessment and certification process of CDx. The IVDR also establishes an important link between the assessment of a CDx and the corresponding medicinal product by requiring the notified body to seek a scientific opinion from the medicines regulator on the suitability of the CDx for use with the concerned medicinal product(s) before issuing an IVD certificate. Whereas the IVDR aims at establishing a robust regulatory framework for IVDs, it is also associated with several challenges, such as insufficient capacity of notified bodies and readiness of manufacturers.

The EMA assessment of avapritinib in the treatment of gastrointestinal stromal tumours harbouring the PDGFRA D842V mutation.

Avapritinib is a protein kinase inhibitor designed to selectively inhibit oncogenic KIT and platelet-derived growth factor receptor alpha (PDGFRA) mutants by targeting the active conformation of the kinase. On 24 September 2020, a marketing authorisation valid through the European Union was issued for avapritinib as treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumours (GIST) harbouring the PDGFRA D842V mutation. The drug was evaluated in an open-label, phase I, first-in-human, dose-escalation, open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of avapritinib in adults with unresectable or metastatic GIST.

Combinations in the first-line treatment of patients with advanced/metastatic renal cell cancer: regulatory aspects.

The therapeutic landscape in the treatment of advanced/metastatic renal cell cancer has evolved over the last 2 years with the advent of immune checkpoint inhibitors. In 2018 and 2019, marketing authorisations valid throughout the European Union were issued for nivolumab and ipilimumab dual checkpoint inhibition and pembrolizumab or avelumab in combination with the tyrosine kinase inhibitor axitinib. These applications presented numerous regulatory challenges.

Sterilization of poly(dimethylamino) ethyl methacrylate-based gene transfer complexes.

Parental administration of polyplex formulations for gene therapy or genetic vaccination requires sterile preparations. The possibilities and limitations of autoclaving, filtration and a combination of both methods for sterilization of poly(2-(dimethylamino) ethyl methacrylate) (pDMAEMA) based gene transfer complexes were assessed. Agarose gel electrophoresis and circular dichroism spectroscopy showed that sterile filtration of polyplexes did not change the topology and integrity of the DNA.