Enzyme Replacement Therapy - Type B
Mount Sinai International Center for Types A and B Niemann-Pick Disease
www.mssm.edu/niemann-pick
Psychosocial Aspects of Patients with Niemann-Pick Disease, Type B
A new research article was recently published online in the American Journal of Medical Genetics titled "Psychosocial Aspects of Patients with Niemann-Pick Disease, Type B."
Some of you will recall that Dr. Wendy Packmann and colleagues from the University of California, San Francisco, attended our Annual Family Conference held in 2005 in Manhattan Beach, California, where they did presentations about their work and interviewed some individuals and family members. Additional interviewing was done following the conference, and we are now seeing the fruits of those efforts.
The abstract/summary of the article is as follows:
Am J Med Genet A. 2009 Nov;149A(11):2430-6.
Psychosocial aspects of patients with Niemann-Pick disease, type B.
Henderson SL, Packman W, Packman S.
Department of Family and Community Medicine, University of California, Davis School of Medicine, Sacramento, California, USA.
Health-care providers have only begun to understand the medical aspects of Niemann-Pick disease type B (NPDB), a relatively rare disease. Even less information is known about the psychological effects of living with NPDB.
Patients with NPDB and their families face numerous psychological stressors including extensive medical testing, uncertainty of diagnosis, living and coping with a chronic illness, and grief and bereavement surrounding this progressively debilitating, and, ultimately, fatal disease. We used a qualitative case study approach to explore the human experiences of NPDB patients and families. To assess psychosocial adjustment, all participants were administered a semi-structured, qualitative interview, as well as quantitative measures.
Five major findings emerged: (1) limited physical activity, social isolation, and peer rejection were identified as significant stressors; (2) stressors had a specific impact during the age span of 10-16 years; (3) parents and adult patients expressed frustration regarding the lack of available information and treatment; (4) patients described close family relationships as a way of coping with illness; and (5) adult patients identified early medical experiences as having a considerable psychological impact.
The results of this investigation highlight and expand awareness of the psychological and social needs of NPDB patients and families. This study calls for a collaborative, multidisciplinary effort in the treatment of these patients and their families.
Copyright 2009 Wiley-Liss, Inc.
PMID: 19877061 [PubMed - in process]
Thank you to all who participated in the study, and congratulations to Dr. Packman and her colleagues for a job well done!
Cate Walsh Vockley
[Nov 16, 2009 mem]
Update from Genzyme on Acid Sphingomyelinase Deficiency (ASMD) Clinical Trials
Phase 2 Enrollment to begin in 2010
A note from Genzyme - October 2009:
We have completed analyses of data from the Phase 1 clinical trial of recombinant human acid sphingomyelinase (rhASM) as a potential treatment for ASMD (also known as Niemann-Pick Disease Types A and B). Key findings were summarized and presented by Dr. Margaret McGovern, the Principal Investigator, on August 31, 2009, in a poster at the International Congress of Inborn Errors of Metabolism in San Diego, California, USA. Dr. McGovern discusses the findings again in an oral presentation at the American Society of Human Genetics annual meeting in Honolulu, Hawaii, USA from October 20 to 24, 2009.
The trial describes the first experience with enzyme replacement therapy in adult patients with ASMD. Eleven patients were treated with single doses of rhASM ranging from 0.03 mg/kg up to 1 mg/kg administered intravenously. The trial design and data analyses were focused on evaluating the safety of rhASM over this range of doses.
Based on the trial findings, Genzyme plans to focus on a within-patient dose escalation design (which means that a patient will start at a lower dose and increase it over time) for Phase 2. The Phase 2 trial design is in development, with patient enrollment expected to begin in 2010.
Genzyme Corporation
500 Kendall Street
Cambridge, MA 02142
Enzyme Replacement Therapy Clinical Trial Update (ASMD/NPD-Type B)
Conclusion of Phase 1
A note from Dr. Margaret McGovern regarding the conclusion of Phase I:
Dear Niemann-Pick Disease Families:
Dr. Wasserstein and I and the entire Niemann-Pick Disease team want to thank the patients who volunteered and made it possible to complete the Phase I study. The poster we presented at the International Congress for Inborn Errors of Metabolism is here for you to see. We also will be presenting these results at the American Society of Human Genetics Meeting in October.
The study was very important. It told us what the safest starting dose for the enzyme should be. It showed that there were some side effects of the drug that usually occurred between 24 and 48 hours after the infusion but that resolved quickly. We also learned what the important blood tests will be to monitor in future trials.
It is a very exciting first step in getting a drug approved for the treatment of Niemann-Pick Disease and we are very happy to share these results with you.
Sincerely,
Margaret M. McGovern, MD, PhD
Professor and Chair of Pediatrics
Stony Brook University School of Medicine
margaret.mcgovern@stonybrook.edu
Poster presented at the International Congress for Inborn Errors of Metabolism
Read the abstract of the presentation
Message from Betsy Bogard of Genzyme: Completion of Phase 1 Clinical Trial
Genzyme is pleased to announce that its Phase 1 clinical trial of recombinant human acid sphingomyelinase (rhASM) as a potential treatment for Acid Sphingomyelinase Deficiency (ASMD, Niemann-Pick Disease Type B) was completed in April 2009. The main purpose of this trial was to evaluate the safety of different doses of rhASM in adults with ASMD. A total of eleven patients were treated with single doses of rhASM ranging from 0.03 mg/kg up to 1 mg/kg administered intravenously. The trial took place at Mt. Sinai Medical Center in New York City.
The results of this trial have given an indication for the best ways to administer the drug intravenously to patients and effectively monitor for potential side effects. Genzyme is completing the Phase 1 data analyses and preparing for a Phase 2 trial that is expected to begin in 2010 and will likely involve giving repeat doses of rhASM. Genzyme plans to disseminate key findings from the Phase 1 trial as they become available.
Completion of the Phase 1 trial marks an important, hard-earned, and long-awaited milestone for the Niemann-Pick B disease community. Our sincere appreciation goes to all the patients who participated in the trial and their families. Genzyme thanks Drs. McGovern and Wasserstein at Mt. Sinai for their leadership of the trial and Jessica Cristian and Erin Starrett for managing data collection activities.
Congratulations to the Niemann-Pick community on achieving this important milestone.
Betsy Bogard
Associate Director, Program Management
Genzyme Corporation
500 Kendall Street, Cambridge, MA 02142
e-mail: betsy.bogard@genzyme.com
www.genzyme.com
Refer to the clinical trial page for more
detailed information:
www.clinicaltrials.gov (study NCT00410566)
http://www.clinicaltrials.gov/ct/show/NCT00410566?order=2
[Sept 14, 2009 mem]
Enzyme Replacement
Therapy - Type B
Clinical Trial Update from Genzyme
Phase 1 Clinical Trial
The Phase 1 clinical trial of recombinant human acid sphingomyelinase (rhASM) as a potential treatment for ASM Deficiency (Niemann-Pick Disease Type B) is ongoing. Nine patients have completed the trial to date. A safety data review was recently completed and we are proceeding with the next planned infusion. Additional patients are being screened and scheduled for visits.
The trial 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 trial’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 a minimum of two patients each rather than three.
More patients are needed to complete this trial. Based on their medical history, potentially eligible individuals for the remaining two dose groups are being contacted by the trial staff. The trial is taking place at Mt. Sinai School of Medicine (MSSM) and is open to eligible individuals worldwide. Participation in the trial requires up to four visits to MSSM. Travel expenses and trial-related medical treatments are being paid for by Genzyme Corporation, which is sponsoring the trial. Anyone interested in participating may visit www.clinicaltrials.gov (study identifier NCT00410566) for more information.
Upon completion of enrollment in this Phase 1 trial, all data will be collected and analyzed. Findings from the Phase 1 trial 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 Niemann-Pick Disease Type B symptoms over time.
Appreciation goes to all the patients who have participated in the trial thus far, as well as to Drs. McGovern, Wasserstein, Schuchman, and Desnick at MSSM for their ongoing work on the trial.
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 Disease Type B. 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.
* 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.
[Oct 29, 2008]
Clinical Trial Update from Genzyme
The Phase 1 clinical study of recombinant human acid aphingomyelinase (rhASM) for treating ASM Deficiency (Niemann-Pic Disease, Type B) is currently ongoing. Eight patients have completed the study to date, with additional patients being screened and scheduled for treatment and assessment visits.
The main purpose of this Phase 1 study is to evaluate the safety of rhASM, an investigational enzyme replacement therapy, given as a single dose to adults with ASM deficiency. During the study, known as a sequential dose escalation study, successive groupd of patients are receiving increasingly higher doses of enzyme. The study includes five total dose groups; three have completed the study and the fourth is in progress. Administration of rhASM has been well-tolerated in all patients to date.
More patients are needed to complete the trial, which is taking place at Mt. Sinai School of Medicine (MSSM) in New York City. Study staff are contacting patients who may be eligible for the remaining two cohorts. The study is open to patients worldwide who meet the study's medical requirements. 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.
Enrollment in the Phase 1 study is expected to be completed this year, with data collection and analysis to follow in 2009. 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 program.
Plans for a multi-national Phase 2 study are currently in development. Findings from the Phase 1 study will be used to help design the Phase 2 trial. We anticipate that the Phase 2 study will be the first opportunity (of at least two generally required for regulatory approval) to evaluate the effect of repeat dosing on various disease symptoms over several months.
[Sept 5, 2008]
Genzyme Corporation has announced the open enrollment of two IRB-approved clinical research studies for individuals with Niemann-Pick disease caused by acid sphingomyelinase deficiency (Types A and B).
The first study is a Phase 1 clinical study of recombinant human acid sphingomyelinase administered as a single dose to adults (18-65 years old) with Niemann-Pick disease Type B. This enzyme replacement study will evaluate a range of sequential doses among approximately 15 patients at one center in the U.S. The primary objective of the study is safety, and the secondary objectives are pharmacokinetics and efficacy. Following a 3-day screening visit, eligible patients will make 3 additional visits to the study site over a 28-day period. One of the study visits involves a 4-day inpatient hospitalization during which the treatment will be administered.
For further information, please contact Genzyme Medical Information at 800-745-4447, option 2 and mention SPHINGO00605. The study is also posted on www.clinicaltrials.gov.
The second study is a non-treatment, chart review study to characterize the natural history of Niemann-Pick disease Types A and B. Findings from this study will help to define the natural progression of the disease and will assist in the selection of endpoints for future clinical treatment studies. Both living and non-living patients with Niemann-Pick disease Types A and B from the US and Canada are eligible for enrollment. Following the informed consent of patients or the next of kin, medical records will be requested and sent to one of the three study sites. De-identified information related to patient demographics, disease history, and health care utilization will be entered into a secure database maintained by Abt Associates, Lexington, MA. Enrollment of new patients will be completed in mid-2007.
For further information, please contact: Genzyme Medical Information at 800-745-4447, option 2 and mention SPHINGO00302.
You can also contact NNPDF for more information about these and other studies.
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