A Review and Comparative Case Study Analysis of Real-World Evidence in European Regulatory and Health Technology Assessment Decision Making for Oncology Medicines.

Objectives: Real-world evidence (RWE) is valuable in supporting regulatory and health technology assessment (HTA) decisions; however, the actual contribution to approvals remains elusive. This study aimed to review RWE approaches and use in oncology medicine approvals in Europe and understand cohesion and discrepancy in the acceptance of the RWE by the European Medicines Agency (EMA) and European HTA bodies.

Methods: This scoping review involved a search of the EMA database, National Institute for Health and Care Excellence (NICE), Gemeinsamer Bundesausschuss (G-BA), and Haute Autorité de Santé (HAS) websites to identify final reports and appraisals for oncology medicines with references to RWE.

New strategies for the development of lipid-lowering therapies to reduce cardiovascular risk.

The very high occurrence of cardiovascular events presents a major public health issue, because treatment remains suboptimal. Lowering LDL cholesterol (LDL-C) with statins or ezetimibe in combination with a statin reduces major adverse cardiovascular events. The cardiovascular risk reduction in relation to the absolute LDL-C reduction is linear for most interventions without evidence of attenuation or increase in risk at low LDL-C levels.

Neuromodulation mediated by the tachykinin NK3-receptor agonist [MePhe7]-neurokinin B in the isolated perfused lung of nonsensitized nonchallenged and ovalbumin-sensitized and -challenged guinea pig.

The neuromodulatory action of the tachykinin NK(3)-receptor agonist [MePhe(7)]-neurokinin B ([MePhe(7)]-NKB) was evaluated on vagal stimulation-induced bronchoconstriction in nonsensitized nonchallenged and ovalbumin (OVA)-sensitized and -challenged guinea pig using the isolated perfused lung preparation. Lungs were placed inside a warmed (37°C) glass chamber and suspended from a force displacement transducer (Grass FT-03) with both vagi connected to a stimulating electrode. Isolated lungs were stimulated at a constant voltage (20 V) and pulse duration (5 ms) with electrical stimulation frequencies ranging from 1 to 128 Hz.

Discovery of SCH 900271, a Potent Nicotinic Acid Receptor Agonist for the Treatment of Dyslipidemia.

Structure-guided optimization of a series of C-5 alkyl substituents led to the discovery of a potent nicotinic acid receptor agonist SCH 900271 (33) with an EC50 of 2 nM in the hu-GPR109a assay. Compound 33 demonstrated good oral bioavailability in all species. Compound 33 exhibited dose-dependent inhibition of plasma free fatty acid (FFA) with 50% FFA reduction at 1.

SAR studies of C2 ethers of 2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-triones as nicotinic acid receptor (NAR) agonist.

Based on in house screening lead compound 1 for the NAR project, SAR studies have been focused on the modification of the C2 ethers of the pyrimidinedione core structure. In this effort, an unpredictable SAR trend was overcome in the alkyl ether and arylalkyl ether series to identify compound 24 with improved in vitro activity compared to nicotinic acid. More consistent and predictable SAR was achieved in the propargyl ether series.