Cerezyme (imiglucerase) / Sanofi - LARVOL DELTA

LEAP: Venglustat in Combination With Cerezyme in Adult Patients With Gaucher Disease Type 3 With Venglustat Monotherapy Extension (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: Genzyme, a Sanofi Company | Trial completion date: Sep 2025 ➔ Oct 2026 | Trial primary completion date: Sep 2025 ➔ Oct 2026

Monotherapy • Trial completion date • Trial primary completion date • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease • GBA

Different and unusual presentation of Gaucher's disease with the same mutation in the glucocerebrosidase enzyme (F266L) in two patients: a case report. (PubMed, J Med Case Rep) - "This report highlights the importance of recognizing the unusual presentation of Gaucher's disease especially in regions with high rates of consanguineous marriage and thalassemia. This knowledge can aid physicians in making accurate diagnoses and providing appropriate treatment."

Journal • Chronic Cough • Cough • Gaucher Disease • Genetic Disorders • Hepatology • Liver Failure • Lysosomal Storage Diseases • Metabolic Disorders • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Type 1 Gaucher Disease

LEAP2MONO: Study to Evaluate the Efficacy and Safety of Venglustat in Adult and Pediatric Patients With Gaucher Disease Type 3 (clinicaltrials.gov) - P3 | N=43 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Pediatrics • Type 1 Gaucher Disease • GBA

EFFICACY AND SAFETY OF IMIGLUCERASE IN CHINESE PATIENTS WITH GAUCHER DISEASE TYPE 3: A SINGLE-ARM, PROSPECTIVE PHASE-IV STUDY (SSIEM 2024) - P4 | "Discussion/Conclusion This first comprehensive study of imiglucerase in Chinese GD3 patients demonstrates that imiglucerase is effective in improving blood and visceral manifestations, mitigated bone disease, and is well-tolerated. Palavras-chave : GD3, imiglucerase, efficacy, safety, phase IV study"

Clinical • P4 data • Gaucher Disease • Genetic Disorders • Hematological Disorders • Infectious Disease • Lysosomal Storage Diseases • Metabolic Disorders • Musculoskeletal Pain • Novel Coronavirus Disease • Orthopedics • Pain • Pediatrics • Rare Diseases

A RANDOMIZED, DOUBLE-BLIND, 2-TREATMENT, 2-PERIOD, CROSSOVER PHASE 1 STUDY TO COMPARE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF ABCERTIN AND CEREZYME® (SSIEM 2024) - "Similar pharmacokinetic, safety and immunogenicity profiles were observed between Abcertin and Cerezyme, suggesting good tolerability of both imiglucerases in healthy subjects."

Clinical • P1 data • PK/PD data • Dermatology • Gaucher Disease • Genetic Disorders • Immunology • Infectious Disease • Metabolic Disorders • Nephrology • Pain • Urticaria

LONG-TERM SAFETY OUTCOMES OF ELIGLUSTAT IN PATIENTS WITH GAUCHER DISEASE: PROSPECTIVE, MULTICENTER, OBSERVATIONAL, POST AUTHORIZATION SAFETY SUB-REGISTRY STUDY (SSIEM 2024) - "Eliglustat was well-tolerated by GD1 patients in real-world and safety profile was consistent with that observed during clinical development."

Clinical • Back Pain • Gaucher Disease • Genetic Disorders • Infectious Disease • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Pneumonia • Respiratory Diseases • Rheumatology • Type 1 Gaucher Disease

SAFETY AND PHARMACOKINETICS OF ELIGLUSTAT ADMINISTERED WITH AND WITHOUT IMIGLUCERASE IN PAEDIATRIC PATIENTS WITH GAUCHER DISEASE TYPE 1/3: ELIKIDS STUDY (SSIEM 2024) - P3 | "Eliglustat was well tolerated in paediatric participants with GD1 and GD3. The safety profile of eliglustat observed in paediatric participants with GD1 and GD3 is in line with the established safety profile seen in adults with GD1. PK exposure is aligned with the target exposure seen in the adult eliglustat clinical trials."

Clinical • PK/PD data • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Pediatrics • Type 1 Gaucher Disease

PREGNANCY OUTCOMES IN IMIGLUCERASE-TREATED PATIENTS WITH GAUCHER DISEASE: REAL-WORLD DATA FROM INTERNATIONAL COLLABORATIVE GAUCHER GROUP (ICGG) GAUCHER REGISTRY PREGNANCY SUB-REGISTRY (SSIEM 2024) - "Most imiglucerase-treated women had live births and healthy neonates. Spontaneous abortion frequency is aligned with published general population rates (12%–24%)."

Clinical • Real-world • Real-world evidence • Anemia • Gaucher Disease • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Thrombocytopenia

EFFICACY OF ELIGLUSTAT ADMINISTERED WITH AND WITHOUT IMIGLUCERASE IN PAEDIATRIC PATIENTS WITH GAUCHER DISEASE TYPE 1 OR 3: ELIKIDS STUDY (SSIEM 2024) - P3 | "The majority of study participants who received eliglustat monotherapy and eliglustat in combination with imiglucerase maintained Gaucher-related clinical parameters within the prespecified therapeutic goals during the 52-week PAP."

Clinical • Gaucher Disease • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Pediatrics • Type 1 Gaucher Disease

Potential Targeting Mechanisms for Bone-Directed Therapies. (PubMed, Int J Mol Sci) - "Although direct recombinant enzymes (e.g., Vimizim for Morquio, Cerezyme for Gaucher, Elaprase for Hunter, Mepsevii for Sly diseases) or hormone infusions (estrogen for osteoporosis and osteoarthritis), traditional gene delivery (e.g., direct infusion of viral or non-viral vectors with no modifications on capsid, envelope, or nanoparticles), and cell therapy strategies (healthy bone marrow or hematopoietic stem cell transplantation) partially improve bone lesions, novel delivery methods must be addressed regarding target specificity, less immunogenicity, and duration in circulation. Targeted drug delivery using organic and inorganic compounds is a promising approach in mostly preclinical settings and future clinical translation. This review comprehensively summarizes the current bone-targeting strategies based on bone structure and remodeling concepts while emphasizing potential approaches for future bone-targeting systems."

Journal • Review • Bone Marrow Transplantation • Immunology • Osteoarthritis • Osteoporosis • Pain • Rheumatology • Transplantation

LONG-TERM SAFETY OUTCOMES OF ELIGLUSTAT IN PATIENTS WITH GAUCHER DISEASE: PROSPECTIVE, MULTICENTER, OBSERVATIONAL, POST AUTHORIZATION SAFETY SUB-REGISTRY STUDY (EHA 2024) - "Eliglustat was well-tolerated by GD1 patients in real-world and safety profile wasconsistent with that observed during clinical development. Table 1. Exposure-adjusted incidence rate of AEs and SAEs for any eliglustat and imiglucerase treatments"

Clinical • Back Pain • Gastroenterology • Gastrointestinal Disorder • Gaucher Disease • Genetic Disorders • Immunology • Infectious Disease • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Pneumonia • Respiratory Diseases • Rheumatology • Type 1 Gaucher Disease

SAFETY, PHARMACOKINETICS, AND EFFICACY OF ELIGLUSTAT ADMINISTERED WITH AND WITHOUT IMIGLUCERASE IN PAEDIATRIC PARTICIPANTS WITH GAUCHER DISEASE TYPE 1 OR 3: THE ELIKIDS STUDY (EHA 2024) - P3 | "Eliglustat was well tolerated in paediatric participants with GD1 and GD3 and no new safety issues wereidentified during the PAP."

Clinical • PK/PD data • Gaucher Disease • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Orthopedics • Pediatrics • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia • Type 1 Gaucher Disease

Qualitative Study of the Patient Experience with Venglustat for Gaucher Disease Type 3 in a Phase 2 Open-Label, Multicenter, Multinational Study (LEAP). (PubMed, Adv Ther) - P2 | "Outcomes from this study provide insights into GD3 symptoms and the early signaling of changes reported during venglustat therapy."

Journal • P2 data • Ataxia • CNS Disorders • Dystonia • Epilepsy • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders • Ophthalmology • Rare Diseases

Phase IV study to evaluate efficacy and safety of imiglucerase treatment in Chinese patients with Gaucher disease type Ⅲ (clinicaltrialsregister.eu) - P4 | N=12 | Sponsor: SANOFI (CHINA) INVESTMENT CO., LTD

New P4 trial • Gaucher Disease • Genetic Disorders • Metabolic Disorders

LEAP2MONO: Study to Evaluate the Efficacy and Safety of Venglustat in Adult and Pediatric Patients With Gaucher Disease Type 3 (clinicaltrials.gov) - P3 | N=40 | Recruiting | Sponsor: Sanofi | Trial completion date: Jan 2026 ➔ Oct 2026 | Trial primary completion date: Dec 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Pediatrics • Type 1 Gaucher Disease • GBA

LEAP2MONO: Study to Evaluate the Efficacy and Safety of Venglustat in Adult and Pediatric Patients With Gaucher Disease Type 3 (clinicaltrials.gov) - P3 | N=40 | Recruiting | Sponsor: Sanofi | Trial primary completion date: Aug 2024 ➔ Dec 2024

Trial primary completion date • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Pediatrics • Type 1 Gaucher Disease • GBA

SEED: Study to Evaluate Efficacy and Safety of Imiglucerase Treatment in Chinese Patients With Gaucher Disease Type Ⅲ (clinicaltrials.gov) - P4 | N=12 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Trial completion • Gaucher Disease • Genetic Disorders • Metabolic Disorders

Pregnancy outcomes in imiglucerase-treated patients with Gaucher disease: real-world data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry Pregnancy Sub-Registry (SSIEM 2023) - P=N/A | "The majority of pregnancies in imiglucerase-treated women resulted in live births and healthy neonates. Spontaneous abortion frequency is aligned with published general population rates (11.4–22%). For imiglucerase, both EMA and FDA recommend ERT before and during pregnancy."

Clinical • Real-world • Real-world evidence • Gaucher Disease • Genetic Disorders • Hematological Disorders • Hepatology • Metabolic Disorders • Thrombocytopenia

ELIKIDS: baseline characteristics from the eliglustat substrate reduction therapy trial in children with Gaucher disease type 1 or type 3 (SSIEM 2023) - P3 | "Overall, most patients enrolled in ELIKIDS have GD1 (86%), are CYP2D6 extensive metabolizers (96%), and were assigned to Cohort 1 (89%) at baseline."

Clinical • Gaucher Disease • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Orthopedics • Pediatrics • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia • Type 1 Gaucher Disease

Osteonecrosis in Gaucher Disease in the era of multiple therapies: biomarker set for risk stratification from a tertiary referral center. (PubMed, Elife) - "No patient receiving eliglustat SRT suffered AVN...These findings exemplify a new approach to biomarker applications in a rare inborn error of metabolism to evaluate clinical outcomes in comprehensively followed patients and will aid identification of GD patients at higher risk of AVN who will benefit from closer monitoring and treatment optimization. Funding: LSD Training Fellowship from Sanofi to MB."

Biomarker • Journal • Gaucher Disease • Genetic Disorders • Metabolic Disorders

SEED: Study to Evaluate Efficacy and Safety of Imiglucerase Treatment in Chinese Patients With Gaucher Disease Type Ⅲ (clinicaltrials.gov) - P4 | N=10 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Gaucher Disease • Genetic Disorders • Metabolic Disorders

Design of a stable human acid-β-glucosidase: towards improved Gaucher disease therapy and mutation classification. (PubMed, FEBS J) - "Recombinant GCase (e.g., Cerezyme®) is produced for use in enzyme replacement therapy for GD and is largely successful in relieving disease symptoms, except for the neurological symptoms observed in a subset of patients...This approach gave remarkably accurate predictions of the enzymatic activity of single nucleotide polymorphisms in the GBA1 gene that are not currently associated with GD or PD. This latter approach could be applied to other diseases to determine risk factors in patients carrying rare mutations."

Journal • CNS Disorders • Gaucher Disease • Gene Therapies • Genetic Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease • GBA

Venglustat combined with imiglucerase for neurological disease in adults with Gaucher disease type 3: the LEAP trial. (PubMed, Brain) - P2 | "There were no deaths, serious adverse events or discontinuations. In adults with GD3 receiving imiglucerase, addition of once-daily venglustat showed acceptable safety and tolerability and preliminary evidence of clinical stability with intriguing but intrinsically inconsistent signals in selected biomarkers, which need to be validated and confirmed in future research."

Journal • Ataxia • CNS Disorders • Gaucher Disease • Genetic Disorders • Hematological Disorders • Metabolic Disorders • Movement Disorders • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia

Eliglustat on Gaucher Disease Type IIIB (clinicaltrials.gov) - P=N/A | N=4 | Completed | Sponsor: National Taiwan University Hospital | Unknown status ➔ Completed

Trial completion • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Type 1 Gaucher Disease • GBA

ELIKIDS: Safety and Efficacy of Eliglustat With or Without Imiglucerase in Pediatric Patients With Gaucher Disease (GD) Type 1 and Type 3 (clinicaltrials.gov) - P3 | N=57 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2023 ➔ Nov 2025

Enrollment closed • Trial primary completion date • Gaucher Disease • Genetic Disorders • Metabolic Disorders • Pediatrics • Type 1 Gaucher Disease • GBA