lucerastat (ACT-434964) / Idorsia - LARVOL DELTA

A Study to Evaluate the Long-term Safety and Tolerability of Lucerastat in Adult Subjects With Fabry Disease (clinicaltrials.gov) - P3 | N=107 | Active, not recruiting | Sponsor: Idorsia Pharmaceuticals Ltd. | Trial completion date: Nov 2025 ➔ Nov 2029 | Trial primary completion date: Oct 2025 ➔ Aug 2029

Trial completion date • Trial primary completion date • Fabry Disease • Genetic Disorders

New drugs available for Fabry disease. (PubMed, Kidney Blood Press Res) - "This review focuses exclusively on newly available drugs and future therapeutic approaches for treating FD, including migalastat, pegunigalsidase alfa, substrate reduction therapy (SRT), and gene therapy. Migalastat provides benefits such as oral administration and non-immunogenicity; however, it is only appropriate for patients with "amenable" GLA variants. The recently approved pegunigalsidase alfa is a pegylated form of α-Gal A manufactured in plant cell cultures, with apparent reduced immune response and prolonged circulating half-life. SRT (venglustat, lucerastat) reduces Gb3 synthesis, helping to normalize metabolic processes while offering certain advantages such as oral administration, non-immunogenic properties, and the possible crossing of the blood-brain barrier. Clinical trials in human and animal model studies are currently investigating ex-vivo and in-vivo gene therapy techniques, showing positive early outcomes. Messages: The ongoing development..."

Journal • Review • Cardiovascular • Fabry Disease • Gene Therapies • Genetic Disorders

Assessment of repurposed compounds against coronaviruses highlights the antiviral broad-spectrum activity of host-targeting iminosugars and confirms the activity of potent directly acting antivirals. (PubMed, Antiviral Res) - "We observed 13 compounds showing antiviral activity against SARS-CoV-2, including seven FDA-approved compounds (remdesivir, boceprevir, amiloride, nafamostat, cisplatin, silmitasertib, and miglustat), and six compounds in pre-clinical and clinical development (tarloxotinib, lucerastat (NB-DGJ), MON-DNJ, NAP-DNJ, NN-DGJ and NN-DNJ). Its activity also extended to another betacoronavirus HCoV OC43, but not alphacoronavirus HCoV 229E. Our cellular screening results add to the body of knowledge on antivirals against coronaviruses and confirm the antiviral efficacy of iminosugars in cellular assays using the human lung-cell line Calu-3."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Lucerastat Effect on Kidney Function in Patients with Fabry Disease: Results from the Phase 3 Clinical Program (KIDNEY WEEK 2024) - P3 | "GCS inhibition with lucerastat might be a novel approach to stabilize or slow the progression of kidney dysfunction, a major therapeutic goal in patients with Fabry disease."

Clinical • P3 data • Fabry Disease • Genetic Disorders • Nephrology • Renal Disease

Efficacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With Fabry Disease (clinicaltrials.gov) - P3 | N=118 | Completed | Sponsor: Idorsia Pharmaceuticals Ltd. | N=182 ➔ 118

Enrollment change • Monotherapy • Fabry Disease • Genetic Disorders

Humanistic Burden of Fabry Disease and Associated Utility Values (ISPOR 2024) - " We conducted an SLR in May 2022 (updated April 2023) to identify studies reporting humanistic burden and utility data in patients with FD who are either untreated or treated with enzyme replacement therapy (ERT) (pegunigalsidase alfa, agalsidase alfa, agalsidase beta), migalastat, venglustat, and lucerastat. The studies identified in this SLR add to our understanding of the humanistic burden of FD since almost 10 years ago. The results suggest utility values increase with ERT treatment, but patient burden has remained stable over time. Long-term data with existing therapies may provide additional insights on outcomes including pain, disease severity, and quality of life."

Fabry Disease • Fatigue • Gastrointestinal Disorder • Genetic Disorders • Pain

Understanding and modifying Fabry disease: Rationale and design of a pivotal Phase 3 study and results from a patient-reported outcome validation study. (PubMed, Mol Genet Metab Rep) - P3 | "Results will be presented in a separate publication. Long-term effects of lucerastat are being assessed in the ongoing open-label extension study (NCT03737214)."

Journal • P3 data • Patient reported outcomes • Chronic Kidney Disease • CNS Disorders • Depression • Fabry Disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Nephrology • Neuralgia • Pain • Psychiatry • Renal Disease

Fabry Disease: current & novel therapeutic strategies. A narrative review. (PubMed, Curr Neuropharmacol) - "During the last two decades, FD-specific treatments, including two enzyme-replacement-therapies (agalsidase alfa and agalsidase beta) and chaperone treatment with migalastat have been approved for use and allowed for symptoms' stabilization or even disease burden reduction...Substrate reduction therapies, including lucerastat and venglustat, have shown promising results in RCTs and may be used either as monotherapy or as complementary therapy to established enzyme-replacement-therapies. More stable enzyme-replacement-therapy molecules that are associated with less adverse events and lower likelihood of neutralizing antibodies formation have also been developed. Ex-vivo and in-vivo gene therapy is being tested in animal models and pilot human clinical trials, with preliminary results showing a favorable safety and efficacy profile."

Clinical • Journal • Review • Fabry Disease • Gene Therapies • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

A Study to Evaluate the Long-term Safety and Tolerability of Lucerastat in Adult Subjects With Fabry Disease (clinicaltrials.gov) - P3; N=108; Active, not recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.; Enrolling by invitation ➔ Active, not recruiting

Clinical • Enrollment closed • Fabry Disease • Genetic Disorders

Efficacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With Fabry Disease (clinicaltrials.gov) - P3; N=182; Completed; Sponsor: Idorsia Pharmaceuticals Ltd.; Active, not recruiting ➔ Completed

Clinical • Monotherapy • Trial completion • Fabry Disease • Genetic Disorders

A Study to Evaluate the Long-term Safety and Tolerability of Lucerastat in Adult Subjects With Fabry Disease (clinicaltrials.gov) - P3; N=108; Enrolling by invitation; Sponsor: Idorsia Pharmaceuticals Ltd.; Recruiting ➔ Enrolling by invitation

Clinical • Enrollment status • Fabry Disease • Genetic Disorders

A Study to Evaluate the Long-term Safety and Tolerability of Lucerastat in Adult Subjects With Fabry Disease (clinicaltrials.gov) - P3; N=108; Recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.; Trial completion date: Jul 2025 ➔ Nov 2025; Trial primary completion date: Jun 2025 ➔ Oct 2025

Clinical • Trial completion date • Trial primary completion date • Fabry Disease

Efficacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With Fabry Disease (clinicaltrials.gov) - P3; N=182; Active, not recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.; Recruiting ➔ Active, not recruiting; N=99 ➔ 182

Clinical • Enrollment change • Enrollment closed • Monotherapy • Fabry Disease

A Study to Evaluate the Long-term Safety and Tolerability of Lucerastat in Adult Subjects With Fabry Disease (clinicaltrials.gov) - P3; N=108; Recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.; Trial completion date: May 2022 ➔ Jul 2025; Trial primary completion date: May 2022 ➔ Jun 2025

Clinical • Trial completion date • Trial primary completion date • Fabry Disease

Efficacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With Fabry Disease (clinicaltrials.gov) - P3; N=99; Recruiting; Sponsor: Idorsia Pharmaceuticals Ltd.; Trial completion date: Jun 2021 ➔ Sep 2021; Trial primary completion date: May 2021 ➔ Aug 2021

Clinical • Monotherapy • Trial completion date • Trial primary completion date • Fabry Disease

Impact of the organic cation transporter 2 inhibitor cimetidine on the single-dose pharmacokinetics of the glucosylceramide synthase inhibitor lucerastat in healthy subjects. (PubMed, Eur J Clin Pharmacol) - P1 | "These results indicate that the single-dose PK of lucerastat are not changed to a clinically relevant extent by cimetidine-mediated OCT2 inhibition, allowing the concomitant use of OCT2 inhibitors with lucerastat without any need for dose adjustment."

Clinical • Journal • PK/PD data • Fabry Disease • Genetic Disorders

The effect of the glucosylceramide synthase inhibitor lucerastat on cardiac repolarization: results from a thorough QT study in healthy subjects. (PubMed, Orphanet J Rare Dis) - P1 | "Lucerastat up to a dose of 4000 mg has no clinically relevant liability to prolong the QT interval or any clinically relevant effect on other ECG parameters. This will be an important factor in the overall benefit-risk assessment of lucerastat in the potential treatment of Fabry disease. Trial registration The study was registered with the ClinicalTrials.gov identifier NCT03832452 (February 6th, 2019, https://clinicaltrials.gov/ct2/show/NCT03832452 ) and the EudraCT number 2018-004546-42 (December 17th, 2018)."

Clinical • Journal • Fabry Disease • Genetic Disorders