266Long-term safety and efficacy data of taliglucerase alfa, a Plantcell-expressed recombinant glucocerebrosidase, in the treatmentof naïve Gaucher disease patients: 36-Month Results

Ari Zimrana, Atul Mehtab, Pilar Giraldoc, Hanna Rosenbaumd, FiorinaGionae, Dominick J. Amatof, Milan Petakovg, Eduardo TerrerosMuñozh, Sergio Eduardo Solorio-Mezai, Gloria Duránj, DeborahElsteina, Raul Chertkoffa, Einat Brill-Almona, aGaucher Clinic, ShaareZedek Medical Center, Hebrew University and Hadassha Medical School,Jerusalem, Jerusalem, Israel, bRoyal Free and University College School ofMedicine, Department of Haematology, Royal Free Hospital, London, UK,cHospital UniversitarioMiguel Servet, Sericio de Haematologia Planta baja,Zaragoza, Spain, dRambam Medical Center, Haematology AmbulatoryServices, Haifa, Israel, eUniversita “La Sapienza,” Hematologia — PediatricSection (1st Floor), Rome, Italy, fMount Sinai Hospital, Toronto, Ontario,Canada, gClinical Center of Serbia, Institute of Endocrinology, Diabetes andMetabolic Disease, Belgrade, Serbia, hCentro Médico Nacional Siglo XXI,Servicio de Hematologia, México City, Mexico, iHospital de EspecialidadesNo. 1, Unidad de Investigacion, colonia Los Paraisos, Leon Guanajuato,Mexico, jPonfificia Universidad Catolica de Chile, Dept. de Pediatria,Santiago, Chile

Taliglucerase alfa is a beta-glucocerebrosidase enzyme replace-ment therapy (ERT) that is approved in the USA and Israel fortreatment of Gaucher disease (GD) in adults and is the first approvedplant cell-expressed biotherapeutic. Pivotal study PB-06-001, was a9-month, randomized, double-blind, dose-ranging (30 and 60 U/kg)trial to assess the safety and efficacy of taliglucerase alfa intreatment-naïve GD patients. Primary and secondary outcomemeasures included change from baseline in spleen and liver volumes,platelet counts, hemoglobin levels, and chitotriosidase activity. Keyinclusion criteria were splenomegaly N8 multiples of normal (MN)and platelet counts b120,000/mm3. At the completion of the 9-month study, patients were eligible to enter an open-label extensionstudy, PB-06-003, with taliglucerase alfa given every 2 weeks at thesame dose as in study PB-06-001. Twenty-six treatment-naïve GDpatients from study PB-06-001 continued double-blind treatment instudy PB-06-003 for an additional 15 months. At 24 total months oftaliglucerase alfa treatment, spleen volume was reduced from 16.4/16.8 MN to 10.0/7.3 MN, liver volume was reduced from 1.7/1.5 to1.3/1.2 MN, and chitotriosidase activity was reduced by 61% and 76%for 30 U/kg and 60 U/kg, respectively. Hemoglobin levels, plateletcounts, and bone disease (assessed by quantitative chemical shiftimaging) were also improved. All treatment-related adverse events

were mild or moderate in severity and transient in nature. In thepresent report, we will provide 36-month interim safety and efficacyresults for treatment-naïve patients from study PB-06-003, whichwill provide the longest multiple-dose ERT study for Gaucherdisease.

doi:10.1016/j.ymgme.2012.11.280

267Intracerebral gene therapy for Sanfilippo syndrome type A

Amina Zinai, Lysogene, Paris, France

Sanfilippo syndrome type A or mucopolysaccharidosis type IIIA(MPSIIIA) is a rare lysosomal storage disease affecting approximately 1in 100,000 births, belonging to the group of lysosomal storage diseases.MPS IIIA is caused by an autosomal recessive genetic defect resulting inthe deficiency of the lysosomal enzyme N-sulphoglucosaminesulphohydrolase (SGSH). SGSH deficiency results in accumulation ofheparan sulfate (HS) oligosaccharides with primary pathologicalexpression occurring in the central nervous system (CNS). Neurologicalfeatures are characterized by mental retardation, severe cognitiveimpairment and invasive behavioral disorders such as severe sleepdisturbances and hyperactivity. Patient's life expectancy is usuallyreduced to less than two decades. There is no treatment for patientsaffected with Sanfilippo syndrome. However, major advances havebeen obtained over the past ten years, demonstrating the feasibility ofAAV-mediated stable gene transfer into the brain resulting in extendedintra-cerebral distribution of enzyme in animal models of Sanfilipposyndrome and correction of major neurological manifestations. LYSO-GENE has developed an intracerebral AAV-based investigationalmedicinal product, SAF-301 for the treatment of Sanfilippo syndrometype A. SAF-301 entered into clinical stage in August 2011. The open-label, single arm, monocentric, phase I/II clinical study is primarilydesigned to evaluate the tolerance and the safety of intracerebral SAF-301 administered in a single neurosurgical session. It is also designed toevaluate exploratory neuropsychological, radiological and biologicalendpoints in the view of future efficacy clinical studies. To date, all theplanned patients have received the treatment. This phase I/II study willbe terminated in June, 2013. Preliminary data on the preclinical andclinical development program of SAF-301 will be presented.

doi:10.1016/j.ymgme.2012.11.281

AbstractsS102