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

Activity of MMV Pandemic Response Box compounds against Mycobacterium ulcerans viability and mycolactone production. (PubMed, Microbiol Spectr) - "By combining this mycolactone-detecting assay with the routinely used resazurin microplate assay, we identified hits (such as pradigastat) that are potential starting points for further development of antivirulence drugs for BU...In addition, we reliably reidentified drugs known to be active against M. ulcerans (such as bedaquiline, Q203, clofazimine, sutezolid, and epetraborole), thus validating our screening approach.IMPORTANCEMycolactone is a key requirement in the pathogenesis of Buruli ulcer (BU)...Here, we used our screening platform, which comprises a simple mycolactone-detecting ELISA combined with a standard resazurin microplate assay, to identify a set of hits from the Medicines for Malaria Venture Pandemic Response Box that could reduce mycolactone expression even without affecting M. ulcerans viability. This screening methodology will contribute to further development of antivirulence drugs for BU."

Journal • Infectious Disease • Malaria

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