title: Seven-year safety and efficacy with velaglucerase alfa for treatment-naïve adult patients with type 1 Gaucher disease.
abstract: Velaglucerase alfa is a human β-glucocerebrosidase approved for Gaucher disease type 1 (GD1) treatment. This report summarizes the 7-year experience of the now-completed phase I/II and extension studies of adult GD1 patients who received velaglucerase alfa. Ten patients who completed the 9-month, phase I/II study entered the extension trial TKT025EXT, of which eight completed this study. Doses were reduced after a cumulative treatment period of 15 to 18 months. Although all patients experienced ≥1 adverse event, no patient withdrew due to a drug-related adverse event or required premedication. No patient developed anti-drug antibodies, compliance remained high (median 98%), and seven of eight eligible patients transitioned to home infusions under supervision by healthcare professionals. Statistically significant improvements were observed for efficacy parameters: mean percentage changes from baseline (95% confidence intervals) were 18% (12%, 24%) for hemoglobin concentration, 115% (66%, 164%) for platelet counts, and -42% (-53%, -31%) and -78% (-94%, -62%) for liver and spleen volumes, respectively. Improvements were also observed for secondary endpoints chitotriosidase and CCL18 levels and exploratory endpoints (bone mineral density [BMD], bone marrow burden [BMB] scores). Normalization to near-normalization of individuals' hemoglobin concentrations, platelet counts, liver volumes, and BMB scores was observed, and there were marked improvements in spleen volumes, biomarkers, and BMD. TKT025EXT represents the longest, prospective clinical trial for GD1 treatment to date and suggests that, despite dose reduction within 18 months of initiating therapy, velaglucerase alfa was generally well tolerated and was associated with marked improvement, including near normalization and/or normalization of key GD1 disease parameters.
authors.affiliation: Shaare Zedek Medical Center, affiliated with the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
authors.affiliation: Shire, Lexington, Massachusetts.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Shire, Lexington, Massachusetts.
authors.forename: Carol
authors.initials: C
authors.lastname: Ogg
authors.affiliation: Shire, Lexington, Massachusetts.
authors.forename: Eric
authors.initials: E
authors.lastname: Crombez
authors.affiliation: Shire, Lexington, Massachusetts.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Cohn
authors.affiliation: Shaare Zedek Medical Center, affiliated with the Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Deborah
authors.initials: D
authors.lastname: Elstein
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D019742:Chemokines, CC / Q000097:blood; D004334:Drug Administration Schedule; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D005962:Glucosylceramidase / Q000008:administration & dosage* / Q000009:adverse effects; D006454:Hemoglobins / Q000378:metabolism; D006596:Hexosaminidases / Q000097:blood; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D010349:Patient Compliance; D010976:Platelet Count; D011446:Prospective Studies; D012646:Self Administration; D013154:Spleen / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: C111792:CCL18 protein, human; D019742:Chemokines, CC; D006454:Hemoglobins; D006596:Hexosaminidases; C086400:chitotriosidase; D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human