Extrapolation in Practice: Lessons from 10 Years with Biosimilar Filgrastim.

Biosimilar filgrastim (Sandoz) was approved in Europe in 2009 and, in 2015, was the first biosimilar approved in the USA. These authorizations were based on the "totality of evidence" concept, an approach that considers data from structural and functional characterization and comparability analysis and non-clinical and clinical studies. For biosimilar filgrastim, phase III confirmatory clinical studies were performed in the most sensitive population, patients with breast cancer undergoing myelosuppressive chemotherapy.

Febrile neutropenia hospitalization due to pegfilgrastim on-body injector failure compared to single-injection pegfilgrastim and daily injections with reference and biosimilar filgrastim: US cost simulation for lung cancer and non-Hodgkin lymphoma.

Guidelines recommend febrile neutropenia (FN) prophylaxis following myelotoxic chemotherapy with either daily injections of filgrastim (Neupogen) or biosimilar filgrastim-sndz (Zarzio/Zarxio), single-injection pegfilgrastim (Neulasta), or pegfilgrastim administered through an on-body injector (PEG-OBI; Neulasta Onpro). PEG-OBI failure rates up to 6.9% have been reported, putting patients at incremental risk for FN and FN-related hospitalization.

Antitumor effects of guanosine-analog phosphonates identified by molecular modelling.

Aiming to address new drug targets, molecular modelling is gaining increasing importance although the prediction capability of the in silico method is still under debate. For an improved treatment of actinic keratosis and squamous cell carcinoma, inhibitors of human DNA polymerase alpha (pol alpha) are developed by docking nucleoside phosphonate diphosphates into the active site of pol alpha. The most promising prodrugs OxBu and OxHex were then prepared by total synthesis and tested in the squamous cancer cell line SCC25.