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Cover of Enzyme-Replacement Therapies for Lysosomal Storage Diseases

Enzyme-Replacement Therapies for Lysosomal Storage Diseases

Technical Briefs, No. 12

Investigators: , PhD, , MS, , MPH, and , PhD.

Blue Cross and Blue Shield Association Technology Evaluation Center, Evidence-based Practice Center
Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 12(13)-EHC154-EF

Structured Abstract


Lysosomal storage diseases (LSDs) comprise about 50 unique monogenic autosomal or X-linked diseases with an estimated combined incidence of 1 in 7,000 to 8,000 live births. They occur secondary to genetic mutations that result in deficiency or reduced activity of native intracellular enzymes that catabolize biological macromolecules. These enzyme defects result in accumulation of specific macromolecular compounds within lysosomes in various tissues and organs, causing progressive damage that can become life-threatening in some diseases. LSD management traditionally involved supportive care measures tailored to disease stage, the organs and systems involved, and the degree of impairment. However, enzyme-replacement therapy (ERT) is now commercially available for six LSDs, typically used lifelong with traditional management practices for each.


The objective of this Technical Brief is to provide an overview of U.S. Food and Drug Administration (FDA)-approved ERT for the treatment of six LSDs. The purpose of a Technical Brief is to report what outcomes (benefits and harms) have been studied for a technology, drug or procedure; it does not enumerate those outcomes. The Technical Brief also addresses research gaps identified during its preparation. It is not intended as a comparative effectiveness review or systematic review that draws conclusions as to the clinical benefits and harms of a drug, device, or procedure. It does not assess study quality or the strength of the body of evidence on specific outcomes.


Four Guiding Questions were used to frame this Technical Brief. An inspection of the literature from 1990 through mid-April 2012 included primary studies, as well as narrative and systematic review articles to create an overview of potential clinical outcomes. Other information sources included dosing and other treatment-related information from the FDA-approved product labels; scientific information packages from the product manufacturers that included unpublished data; and, interviews with physician Key Informants and patient advocates.


Published clinical studies report a variety of outcomes associated with nine FDA-approved ERT products. They include disease-specific intermediate outcomes, such as plasma or urinary levels of macromolecular compounds. Others were common hematological measures (e.g., anemia, thrombocytopenia), bone pain and skeletal abnormalities, renal function, cardiac function, pulmonary function, growth, and walking tests. Harms reported to the FDA and in clinical studies were primarily allergic, including infusion-associated reactions and anaphylaxis. Immunogenic responses, primarily an IgG-type antibody response and neutralizing antibodies, have been reported. This Technical Brief identified a number of research gaps, including the need for comparative effectiveness studies, dose optimization, optimal timing for initiation of ERT, and mechanisms involved in uptake and distribution of ERT products.


Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services1, Contract No. 290-2007-10058-I, Prepared by: Blue Cross and Blue Shield Association Technology Evaluation Center, Evidence-based Practice Center, Chicago, IL

Suggested citation:

Ratko TA, Marbella A, Godfrey S, Aronson N. Enzyme-Replacement Therapies for Lysosomal Storage Diseases Technical Brief. No. 12. (Prepared by Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center under Contract No. 290-2007-10058-I.) Rockville, MD: Agency for Healthcare Research and Quality. January 2013.

This report is based on research conducted by the Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290 2007-10058-I). The findings and conclusions in this document are those of the author(s), who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.

This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.


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Bookshelf ID: NBK117219PMID: 23390670
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