RG7893 / Roche, Xenon - LARVOL DELTA

Discovery of Acyl-sulfonamide Na1.7 Inhibitors GDC-0276 and GDC-0310. (PubMed, J Med Chem) - "To further derisk the predicted human pharmacokinetics and enable QD dosing, additional optimization of the scaffold was conducted, resulting in the discovery of a novel series of N-benzyl piperidine Na1.7 inhibitors. Improvement of the metabolic stability by blocking the labile benzylic position led to the discovery of GDC-0310 (2), which possesses improved Na selectivity and pharmacokinetic profile over 1."

Journal • Pain

Isothermal Crystallization Monitoring and Time-Temperature-Transformation of Amorphous GDC-0276: Differential Scanning Calorimetric and Rheological Measurements. (PubMed, Mol Pharm) - "From the crystallization kinetics modeling, the solid-liquid interfacial surface tension σ was obtained for GDC-0276 and was compared with that obtained from the melting point depression measurements of the material confined in nanoporous glasses. The differences between the values from the two methods are discussed."

Journal • CNS Disorders • Depression • Psychiatry

Xenon Pharma will offer business, milestone update at Needham Conference (Benzinga) - "Xenon Pharmaceuticals...today announced that Dr. Simon Pimstone...will present a business update, including progress toward milestones, at the Needham Healthcare Conference at 12:50 pm ET on Tuesday, April 12, 2016, in New York City....Xenon's partner Teva Pharmaceutical Industries Ltd. is currently conducting a...Phase 2b clinical trial for TV-45070 in patients with post-herpetic neuralgia....Teva updated its forecast and now expects results in the first half of 2017....Genentech intends to initiate a Phase 2 clinical trial (for GDC-0276) in 2016."

Anticipated conference • Anticipated new P2 trial • Anticipated P2b data • Pain

Xenon Pharmaceuticals reports 2014 financial results and provides corporate update (GlobeNewswire) - "Xenon's partner Teva...is currently conducting a 300-patient...Phase 2b clinical trial for TV-45070 in osteoarthritis. Data from the trial are expected in the third quarter of 2015....Has initiated a Phase 2b clinical trial of TV-45070 in patients with post-herpetic neuralgia, or PHN. The first patient is anticipated to be dosed in March 2015. The anticipated completion date for the Phase 2b clinical trial is mid-2016....The Phase 1 clinical trial (for GDC-0276) has recently been expanded and is expected to complete enrollment in the second half of 2015."

Anticipated P2b data • Anticipated trial completion date • Anticipated trial initiation date • Pain

A Case Study of Overestimating Absorption and Circulating Metabolites Due to the Preferential Absorption of Radiolabeled Drug in a Mass Balance Study. (PubMed, Drug Metab Lett) - "Assuming the radiotracer was proportional to total drug throughout a radiolabeled study was not valid in a 14C study in beagle dogs. This presumably resulted from unequal absorption of the radiotracer and nonradiolabeled test articles from the oral dose due to inequivalent solid forms. We were able to provide a more accurate description of the AME of GDC-0276 in dogs by characterizing the differential absorption of the radiotracer."

Clinical • Journal

Safety, Tolerability, and Pharmacokinetics of GDC-0276, a Novel Na1.7 Inhibitor, in a First-in-Human, Single- and Multiple-Dose Study in Healthy Volunteers. (PubMed, Clin Drug Investig) - "GDC-0276 exhibited a safety and pharmacokinetic profile that supports its future investigation as a potential therapeutic for pain."

Clinical • Journal • P1 data • PK/PD data