Gene Therapy With Modified Autologous Hematopoietic Stem Cells for the Treatment of Patients With Mucopolysaccharidosis Type I, Hurler Variant

Summary

This is a phase I/II study evaluating safety and efficacy of autologous hematopoietic stem and progenitor cells genetically modified with IDUA lentiviral vector encoding for the human α-L-iduronidase gene for the treatment of patients affected by Mucopolysaccharidosis Type I, Hurler variant

Timeline

Start

2018-05-11

Primary completion

2035-01

Completion

2035-03

Outcome

Met primary endpoint

release “First Primary Outcome Measure Met with All Eight Patients Achieving Hematologic Engraftment” orchard-tx.com ↗

release “As previously reported, all eight participants achieved the primary endpoint of supraphysiologic blood alpha-L-iduronidase (IDUA) activity.” orchard-tx.com ↗

Publications

• Background Consiglieri G, Tucci F, De Pellegrin M, Guerrini B, Cattoni A, Risca G, Scarparo S, Sarzana M, Pontesilli S, Mellone R, Gasperini S, Galimberti S, Silvani P, Filisetti C, Darin S, Forni G, Miglietta S, Santi L, Facchini M, Corti A, Fumagalli F, Cicalese MP, Calbi V, Migliavacca M, Barzaghi F, Ferrua F, Gallo V, Recupero S, Canarutto D, Doglio M, Tedesco L, Volpi N, Rovelli A, la Marca G, Valsecchi MG, Zancan S, Ciceri F, Naldini L, Baldoli C, Parini R, Gentner B, Aiuti A, Bernardo ME. Early skeletal outcomes after hematopoietic stem and progenitor cell gene therapy for Hurler syndrome. Sci Transl Med. 2024 May;16(745):eadi8214. doi: 10.1126/scitranslmed.adi8214. Epub 2024 May 1.
• Background Gentner B, Tucci F, Galimberti S, Fumagalli F, De Pellegrin M, Silvani P, Camesasca C, Pontesilli S, Darin S, Ciotti F, Sarzana M, Consiglieri G, Filisetti C, Forni G, Passerini L, Tomasoni D, Cesana D, Calabria A, Spinozzi G, Cicalese MP, Calbi V, Migliavacca M, Barzaghi F, Ferrua F, Gallo V, Miglietta S, Zonari E, Cheruku PS, Forni C, Facchini M, Corti A, Gabaldo M, Zancan S, Gasperini S, Rovelli A, Boelens JJ, Jones SA, Wynn R, Baldoli C, Montini E, Gregori S, Ciceri F, Valsecchi MG, la Marca G, Parini R, Naldini L, Aiuti A, Bernardo ME; MPSI Study Group. Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome. N Engl J Med. 2021 Nov 18;385(21):1929-1940. doi: 10.1056/NEJMoa2106596.
• Background Tucci F, Uria Oficialdegui ML, Consiglieri G, Cossutta M, Filisetti C, Fumagalli F, Butera C, Santangelo R, Colombo M, Manitto MP, Stoppani M, Martina E, Dane G, Camesasca C, Risca G, De Pellegrin M, Scarparo S, Sarzana M, Puricelli C, Galimberti S, Darin S, Silvani P, Bonanomi S, Gasperini S, Naldini L, Gentner B, Parini R, Del Toro M, Diaz-de-Heredia C, Aiuti A, Bernardo ME. Non-neurological, non-skeletal outcomes after hematopoietic stem and progenitor cell-gene therapy (OTL-203) for Hurler syndrome. Mol Ther. 2026 Jan 7;34(1):443-454. doi: 10.1016/j.ymthe.2025.09.042. Epub 2025 Sep 27.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	OTL-203	Cell therapy	4e+06 cells/kg	Intravenous
Subject	OTL-203	Cell therapy	8e+06 cells/kg	Intravenous
Subject	OTL-203	Cell therapy	3.5e+07 cells/kg	Intravenous

Indications