Brian Demeules reports that the Type B clinical trial for enzyme replacement therapy has been approved by the FDA and recruiting has started! Additional information on the trial can be found at the NIH Clinical Trials site (or search the site for "Niemann-Pick enzyme replacement"). A description of Phase 1 of the trial was included in the Fall 2006 NNPDF Newsletter (see article below).
Genzyme Corp. developed the enzyme replacement therapy and has worked hard to obtain FDA approval for this trial. There have been repeated delays as the FDA requested more information about clincial progression of Type B, manufacturing, and other issues. NNPDF has invited Genzyme representatives to the annual Family Conference for many years and the collaboration of Genzyme, Mount Sinai, and the Type B families has led to this exciting advance.
From Genzyme, Fall 2006
NIEMANN-PICK DISEASE B UPDATE
"Genzyme and our collaborators, Drs. Desnick, McGovern, Wasserstein, and Schuchman at Mt. Sinai School of Medicine (MSSM) have reached an important milestone in the development of recombinant human sphingomyelinase (rhASM) for treating ASM Deficiency (Niemann-Pick Disease, Type B). Everything is in place to begin the first ever clinical trial of rhASM. A multi-day training session for all of the study personnel at MSSM is scheduled for the end of September. This session will go over all of the operational details of the trial with everyone who will be involved in its conduct. Patient screening will commence shortly after the training session and treatment will follow once appropriate patients are identified.
The Phase 1 clinical trial will be conducted entirely at MSSM. The primary objective of the study is to assess the safety of rhASM when administered once to adults with ASM deficiency. Individuals who, based on their medical records, are potentially eligible for the trial will be contacted by Dr. McGovern or her staff to determine their interest in participating. Those who choose to do so will be screened at MSSM to determine whether they meet all of the eligibility criteria for the study.
Groups of patients will receive a single administration of different doses of enzyme starting with the lowest dose and proceeding to the highest. This type of study is called a sequential dose escalation study because the data from each group of patients must be analyzed before deciding whether to proceed to the next. The decision about whether to proceed to the next dose level will be based on pre-specified criteria. Under the best of circumstances, it is expected to take at least 9 months to enroll all of the patients into this study and several months after that to collect and analyze all of the data. The data from this study would then be used to design future studies that will measure the effectiveness of the investigational drug. Such efficacy studies will take several years to complete and must be submitted to regulatory authorities around the world as part of comprehensive drug registration package. Additional information about this study will be available soon at www.clinicaltrials.gov.
Genzyme is looking forward to the participation of patients in this next crucial step in the development of rhASM. (www.genzyme.com)"
Paul L Kaplan, Ph.D., M.B.A. Senior Director of Program Management Genzyme Corporation
From the Webmaster, July 2003
Genzyme continues in discussions with the FDA and other regulatory boards to finalize the protocol for the Enzyme Replacement Therapy (ERT) clinical trial for Niemann-Pick Type B. There are several levels of approval which must be received before the trial can begin. At the NNPDF Family Conference in July 2003, Paul Kaplan, Genzyme's Senior Director of Program Management, indicated that the final version of the protocol was expected to be completed shortly and submitted for approval. It is estimated that the trial can begin quickly once regulatory approval is received.
From Genzyme, October 2002
Type B Baseline Survey
"Genzyme has now completed enrollment of patients into a multi-national survey of Niemann-Pick Disease, Type B patients. This study included a significant effort by Dr. Ed. Schuchman and Dr. Robert Desnick at the Mount Sinai School of Medicine in New York as reported in earlier issues of this newsletter, and was designed to collect baseline data on the disease and it's impact on patient's lives, but not to evaluate a particular therapy. Genzyme has decided to extend the survey study in order to learn more about the progression of Niemann-Pick Disease, Type B and some patients have returned for annual follow-up evaluations. These data will be valuable in understanding the course of the disease and the impact of therapy. The extension of the survey study will be conducted in parallel with other clinical trials that evaluate potential therapeutic treatment. Participation in the survey study or its extension is neither a requirement nor a guarantee of inclusion in future clinical trials.
The survey study provided an impressive amount of data documenting the medical condition of NPD-B patients around the world. Genzyme continues to analyse the data, but the data have already yielded new insights into the disease. The information gained from the study is now being used to design the initial clinical studies of enzyme replacement therapy for Niemann-Pick Disease patients with acid sphingomyelinase deficiency. The primary goal of the initial studies will be to establish the safety of ERT in patients with a spectrum of manifestations of NPD. Other goals are to select an optimal dose for future studies and determine what disease parameters must be measured to prove the efficacy of the drug to regulatory authorities in future trials.
The details of the initial studies are still under discussion, but are expected to be finalised before the end of this year. The studies are being designed in consultation with an international panel of experts, and will eventually form part of the package of clinical data necessary to support international approval of a product. Genzyme's goal is to obtain international regulatory approval of a safe and effective therapy for all Niemann-Pick Disease, Type B patients as quickly as possible."
Paul Kaplan, Ph.D., M.B.A., Senior Director of Program Management, Genzyme Corporation
