lademirsen (RG-012) / Regulus Therapeutics - LARVOL DELTA

A Randomized Controlled Clinical Trial Testing Effects of Lademirsen on Kidney Function Decline in Adults with Alport Syndrome. (PubMed, Clin J Am Soc Nephrol) - "While anti-microRNA-21 therapy with lademirsen was generally well-tolerated with an acceptable safety profile, no meaningful improvement in rate of kidney function decline in adults with Alport syndrome at risk of rapidly progressive disease was observed."

Clinical • Journal • Genetic Disorders • Hematological Disorders • Infectious Disease • Nephrology • Pain • Renal Disease • Respiratory Diseases • MIR21

HERA: Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2 | N=43 | Terminated | Sponsor: Genzyme, a Sanofi Company | Trial completion date: Dec 2023 ➔ Sep 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Sep 2022; The results of the futility analysis led to the study termination. No unexpected safety findings were identified.

Trial completion date • Trial primary completion date • Trial termination • Genetic Disorders • CST3 • LCN2 • MIR21

Computational analysis of marine algal compounds for obesity management against pancreatic lipase. (PubMed, J Biomol Struct Dyn) - "Based on the binding energy, the following compounds RG012 (-10.15 kcal/mol), LIG42 (-9.7 kcal/mol), BC010 (-8.47 kcal/mol), RL073 (-8.2 kcal/mol), and LIG46 (-8.03 kcal/mol) were selected exhibiting higher binding affinity when compared to the standard drug (Orlistat) and hence these compounds were subjected to molecular dynamics simulation using GROMACS. BC010 complex revealed a stable interaction within the binding pocket and the binding free energy is -158.208 kJ/mol which is higher when compared to other complexes in 100 ns simulation. BC010 ((7S,11S,12S,14R)-4',14-dimethoxyamentol) from brown algae Cystophora fibrosa could be considered as a potential drug candidate to suppress obesity by inhibiting pancreatic lipase.Communicated by Ramaswamy H. Sarma."

Journal • Genetic Disorders • Obesity

Novel Therapies for Alport Syndrome. (PubMed, Front Med (Lausanne)) - "Ramipril was found in retrospective studies to delay the onset of ESKD and was recently demonstrated to be safe and effective in children and adolescents, supporting that early initiation of Renin Angiotensin Aldosterone System (RAAS) blockade is very important. Our review will include bardoxolone methyl, an oral NRf2 activator; lademirsen, an anti-miRNA-21 molecule; sparsentan, dual endothelin type A receptor (ETAR) and angiotensin 1 receptor inhibitor; atrasentan, oral selective ETAR inhibitor; lipid-modifying agents, including cholesterol efflux transporter ATP-binding cassette A1 (ABCA1) inducers, discoidin domain receptor 1 (DDR1) inhibitors and osteopontin blocking agents; the antimalarial drug hydroxychloroquine; the antiglycemic drug metformin and the active vitamin D analog paricalcitol. Future genomic therapeutic strategies such as chaperone therapy, genome editing and stem cell therapy will also be discussed."

Journal • Review • Genetic Disorders • Glomerulonephritis • Infectious Disease • Nephrology • Renal Disease • Collagen Type IV • DDR1 • MIR21 • SPP1

Anti-microRNA-21 Therapy on Top of ACE Inhibition Delays Renal Failure in Alport Syndrome Mouse Models. (PubMed, Cells) - "Here, we investigated the nephroprotective effects of Lademirsen anti-miR-21 therapy...In conclusion, significant additive effects were detected for the combination of anti-miR-21 and ACEi therapies on kidney function, pathology and survival in Alport mouse models, as well as a strong differential effect of anti-miR-21 on the renal expression of fibrotic factors. These results support the addition of anti-miR-21 to the current standard of care (ACEi) in ongoing clinical trials in patients with Alport syndrome."

Journal • Preclinical • Fibrosis • Genetic Disorders • Immunology • Nephrology • Renal Disease • Collagen Type IV • MIR21

HERA: Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2 | N=43 | Active, not recruiting | Sponsor: Genzyme, a Sanofi Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • CST3 • LCN2 • MIR21 • TGFB1

Antifibrotic Agents for the Management of CKD: A Review. (PubMed, Am J Kidney Dis) - "Pirfenidone, a drug used for idiopathic pulmonary fibrosis (IPF), is undergoing a phase 2 trial for kidney fibrosis. Other drugs in use or being tested for IPF (e.g. nintedanib, PRM-151, epigallocatechin gallate) are also potential candidates to treat kidney fibrosis. Novel therapeutic approaches may include antagomirs (e.g. lademirsen) or drugs targeting IL-11 or NKD2. Reversing dysfunctional tubular cell metabolism that leads to kidney fibrosis offers additional therapeutic opportunities. However, any future drug targeting fibrosis of the kidneys should demonstrate added benefit to a novel standard of care combining renin-angiotensin system with mineralocorticoid receptor (e.g. finerenone) blockade or with SGLT2 inhibitors."

Journal • Review • Chronic Kidney Disease • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Nephrology • Pulmonary Disease • Renal Disease • Respiratory Diseases

HERA: Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Genzyme, a Sanofi Company; Trial completion date:Aug 2027 ➔ Dec 2023; Trial primary completion date: Aug 2027 ➔ Dec 2023

Clinical • Trial completion date • Trial primary completion date • Genetic Disorders • CST3 • LCN2 • MIR21 • TGFB1

HERA: Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Genzyme, a Sanofi Company; Trial completion date: Dec 2023 ->Aug 2027; Trial primary completion date: Dec 2023 ➔ Aug 2027

Clinical • Trial completion date • Trial primary completion date • Genetic Disorders • CST3 • LCN2 • MIR21 • TGFB1

HERA: Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Genzyme, a Sanofi Company; Trial completion date: Aug 2027 ➔ Dec 2023; Trial primary completion date: Aug 2027 ➔ Dec 2023

Clinical • Trial completion date • Trial primary completion date • Genetic Disorders • CST3 • LCN2 • MIR21 • TGFB1

HERA: Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Genzyme, a Sanofi Company; Trial completion date: Dec 2023 ➔ Aug 2027; Trial primary completion date: Dec 2023 ➔ Aug 2027

Clinical • Trial completion date • Trial primary completion date • Genetic Disorders • CST3 • LCN2 • MIR21 • TGFB1

HERA: Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Genzyme, a Sanofi Company; Trial completion date: Jun 2023 ➔ Dec 2023; Trial primary completion date: Jun 2023 ➔ Dec 2023

Clinical • Trial completion date • Trial primary completion date • Genetic Disorders • CST3 • LCN2 • MIR21 • TGFB1

Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2; N=40; Suspended; Sponsor: Regulus Therapeutics Inc.; Trial primary completion date: Nov 2018 ➔ Dec 2019

Clinical • Trial primary completion date • CST3 • LCN2 • MIR21

Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Genzyme, a Sanofi Company; Suspended ➔ Recruiting; Trial completion date: Dec 2019 ➔ Mar 2023; Trial primary completion date: Dec 2019 ➔ Mar 2023

Clinical • Enrollment open • Trial completion date • Trial primary completion date • CST3 • LCN2 • MIR21

Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2; N=45; Suspended; Sponsor: Genzyme, a Sanofi Company; Recruiting ➔ Suspended

Clinical • Trial suspension • CST3 • LCN2 • MIR21

Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: Genzyme, a Sanofi Company; Suspended ➔ Recruiting

Clinical • Enrollment open • CST3 • LCN2 • MIR21

Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (clinicaltrials.gov) - P2; N=40; Suspended; Sponsor: Regulus Therapeutics Inc.; Recruiting ➔ Suspended

Clinical • Trial suspension • CST3 • LCN2 • MIR21

A Study of RG-012 in Subjects With Alport Syndrome (clinicaltrials.gov) - P1; N=4; Completed; Sponsor: Genzyme, a Sanofi Company; Active, not recruiting ➔ Completed

Trial completion