pradigastat (LCQ908) / Novartis, Anji Pharma - LARVOL DELTA

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety and Tolerability of ANJ908, a Novel DGAT1 Inhibitor, in Patients With Chronic Idiopathic Constipation (ACG 2022) - "A total of 191 patients were randomized. Patients were 77.9% female, with a mean (SD) age and BMI of 42.2 (14.4) years and 23.2 (4.36) kg/m 2 , respectively. ANJ908 increased the mean (SE) placebo-subtracted number of SBM/week by +2.28 (0.75; p = 0.0027) and +3.10 (0.74; p < 0.0001) and CSBM/week by +1.53 (0.70; p = 0.03) and +1.81 (0.70; p = 0.01), respectively at week 4."

Clinical • P2 data • Constipation • Gastroenterology • Gastrointestinal Disorder

A Proof of Concept Study of Pradigastat in Patients With Functional Constipation (clinicaltrials.gov) - P2 | N=181 | Completed | Sponsor: Anji Pharma | Recruiting ➔ Completed | Trial primary completion date: Jan 2022 ➔ Apr 2022

Trial completion • Trial primary completion date • Constipation • Gastroenterology • Gastrointestinal Disorder

A novel low systemic diacylglycerol acyltransferase 1 inhibitor, Yhhu2407, improves lipid metabolism. (PubMed, Eur J Pharm Sci) - "Here we report a novel DGAT1 inhibitor, Yhhu2407, which showed a stronger DGAT1 inhibitory activity (IC = 18.24 ± 4.72 nM) than LCQ908 (IC = 78.24 ± 8.16 nM) in an enzymatic assay and led to a significant reduction in plasma TG after an acute lipid challenge in mice...In vivo study also disclosed that Yhhu2407 exerted a beneficial effect on regulating plasma TG and lipoprotein levels in rats, and effectively ameliorated high-fat diet (HFD)-induced dyslipidemia in hamsters. In conclusion, we identified Yhhu2407 as a novel DGAT1 inhibitor with potent efficacy on improving lipid metabolism in rats and HFD-fed hamsters without causing obvious adverse effects."

Journal • CNS Disorders • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • APOB

A Proof of Concept Study of Pradigastat in Patients With Functional Constipation (clinicaltrials.gov) - P2; N=180; Recruiting; Sponsor: Anji Pharma

Clinical • New P2 trial • Constipation • Gastroenterology • Gastrointestinal Disorder

DGAT1 inhibitors protect pancreatic β-cells from palmitic acid-induced apoptosis. (PubMed, Acta Pharmacol Sin) - "We showed that DGAT1 inhibitors (4a and LCQ908) at the concentration of 1 μM significantly ameliorated palmitic acid (PA)-induced apoptosis in MIN6 pancreatic β-cells and primary cultured mouse islets; oral administration of a DGAT1 inhibitor (4a) (100 mg/kg) for 4 weeks significantly reduced the apoptosis of pancreatic islets in db/db mice...Furthermore, we revealed that pretreatment with 4a (1 μM) significantly alleviated PA-induced intracellular lipid accumulation, endoplasmic reticulum (ER) stress, and proinflammatory responses in MIN6 cells, which might contribute to the protective effects of DGAT1 inhibitors on pancreatic β-cells. These findings provided a better understanding of the antidiabetic effects of DGAT1 inhibitors."

Journal • CNS Disorders • Diabetes • Immunology • Metabolic Disorders • Type 2 Diabetes Mellitus

Extension to a randomized, double-blind, placebo controlled study of LCQ908 in subjects with familial chylomicronemia syndrome (clinicaltrials.gov) - P3, N=42; Sponsor: Novartis; Not yet recruiting -> Recruiting.

Enrollment open • Dyslipidemia

R and D Investor Day (Novartis) - Anticipated data read-out from pivotal study for metabolic diseases by October 2013; Anticipated filing in EU and US for metabolic diseases in between November 2013-October 2014

Anticipated clinical data • Anticipated EU regulatory • Anticipated FDA event • Dyslipidemia

Extension to a randomized, double-blind, placebo controlled study of LCQ908 in subjects with familial chylomicronemia syndrome (clinicaltrials.gov) - P3, N=42; Sponsor: Novartis; Recruiting; Completion date: Mar 2014 -> Feb 2015.

Trial completion date • Atherosclerosis • Dyslipidemia

Novartis: Investor Day (Novartis) - Anticipated filing in US for familial chylomicronemia syndrome between Dec 2014 - Nov 2015; Anticipated filing in EU for familial chylomicronemia syndrome between Dec 2014 - Nov 2015; Anticipated approval in US for familial chylomicronemia syndrome between Dec 2014 - Nov 2015; Anticipated approval in EU for familial chylomicronemia syndrome between Dec 2014 - Nov 2015

Anticipated EU regulatory • Anticipated FDA event • Dyslipidemia