Phase 1 Clinical Trial - Report by Betsy Bogard - LSD Management Programme - Genzyme Corporation

The Phase 1 clinical study of recombinant human acid sphingomyelinase (rhASM) as a potential treatment for ASM Deficiency (Niemann-Pick Disease, Type B) is ongoing. Eight patients have completed the study to date, two patients are undergoing treatment and assessment visits, and additional patients are being screened.

The study was originally planned to include 15 total patients divided into five separate dose groups of three patients each, with each group receiving a successively higher dose of enzyme. Given the challenges of finding patients who meet the study’s strict inclusion and exclusion criteria, in June Genzyme proposed a reduction in trial size from 15 to 12 patients. This proposal was submitted to and approved by the US Food and Drug Administration (FDA), the regulatory agency overseeing the trial. The third, fourth, and fifth dose groups now require two patients each rather than three.

More patients are needed to complete the trial. Based on their medical history, potentially eligible individuals for the remaining two cohorts are being contacted by the study staff. The study is taking place at Mt. Sinai School of Medicine (MSSM) and is open to eligible patients worldwide. Participation in the trial requires up to four visits to MSSM. Travel expenses and study-related medical treatments are being paid for by Genzyme Corporation, which is sponsoring the study. Anyone interested in participating may visit www.clinicaltrials.gov (study identifier NCT00410566) for more information.

Upon completion of enrollment in the Phase 1 study, all data will be collected and analyzed. Findings from the Phase 1 study will be used to help design a multi-national Phase 2 trial in which we expect to evaluate the effect of repeat dosing on various disease symptoms over time.

Appreciation goes to all the patients who have participated in the study thus far, as well as to Drs. McGovern, Wasserstein, Schuchman, and Desnick at MSSM for their ongoing work on the study.

Survey Study
Findings from the baseline analyses of the prospective, cross-sectional survey study of the natural history of Niemann-Pick Disease Type B were recently published in the journal Pediatrics.* These analyses were led by Dr. McGovern and documented the multisystem involvement and clinical variability of Niemann-Pick B disease. Among other findings, the analyses showed a correlation between spleen volume and disease severity, suggesting that spleen volume may be a useful surrogate end point in treatment trials. Biomarkers such as chitotriosidase may also play a role in monitoring patient treatment responses.

Betsy Bogard
LSD Program Management
Genzyme Corporation
500 Kendall Street, Cambridge, MA 02142
e-mail: betsy.bogard@genzyme.com
www.genzyme.com

* McGovern MM, Wasserstein MP, Giugliani R, Bembi B, Vanier MT, Mengel E, Brodie SE, Mendelson D, Skloot G, Desnick RJ, Kuriyama N, Cox GF. A prospective, cross-sectional survey study of the natural history of Niemann-Pick disease type B. Pediatrics. 2008 Aug;122(2):e341-9. Epub 2008 Jul 14.