Abstract | BACKGROUND: METHODS: We enrolled infants and young children with life-threatening or debilitating perinatal or infantile hypophosphatasia in a multinational, open-label study of treatment with ENB-0040. The primary objective was the healing of rickets, as assessed by means of radiographic scales. Motor and cognitive development, respiratory function, and safety were evaluated, as well as the pharmacokinetics and pharmacodynamics of ENB-0040. RESULTS: Of the 11 patients recruited, 10 completed 6 months of therapy; 9 completed 1 year. Healing of rickets at 6 months in 9 patients was accompanied by improvement in developmental milestones and pulmonary function. Elevated plasma levels of the TNSALP substrates inorganic pyrophosphate and pyridoxal 5'-phosphate diminished. Increases in serum parathyroid hormone accompanied skeletal healing, often necessitating dietary calcium supplementation. There was no evidence of hypocalcemia, ectopic calcification, or definite drug-related serious adverse events. Low titers of anti-ENB-0040 antibodies developed in four patients, with no evident clinical, biochemical, or autoimmune abnormalities at 48 weeks of treatment. CONCLUSIONS:
ENB-0040, an enzyme-replacement therapy, was associated with improved findings on skeletal radiographs and improved pulmonary and physical function in infants and young children with life-threatening hypophosphatasia. (Funded by Enobia Pharma and Shriners Hospitals for Children; ClinicalTrials.gov number, NCT00744042.).
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Authors | Michael P Whyte, Cheryl R Greenberg, Nada J Salman, Michael B Bober, William H McAlister, Deborah Wenkert, Bradley J Van Sickle, Jill H Simmons, Terence S Edgar, Martin L Bauer, Mohamed A Hamdan, Nick Bishop, Richard E Lutz, Mairead McGinn, Stanley Craig, Jean N Moore, John W Taylor, Robert H Cleveland, William R Cranley, Ruth Lim, Tom D Thacher, Jill E Mayhew, Matthew Downs, José Luis Millán, Alison M Skrinar, Philippe Crine, Hal Landy |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 366
Issue 10
Pg. 904-13
(Mar 08 2012)
ISSN: 1533-4406 [Electronic] United States |
PMID | 22397652
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Immunoglobulin G
- Recombinant Fusion Proteins
- Alkaline Phosphatase
- asfotase alfa
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Topics |
- Alkaline Phosphatase
(administration & dosage, pharmacology, therapeutic use)
- Biological Availability
- Bone and Bones
(diagnostic imaging, drug effects)
- Child, Preschool
- Enzyme Replacement Therapy
(adverse effects)
- Female
- Humans
- Hypophosphatasia
(complications, drug therapy)
- Immunoglobulin G
(administration & dosage, pharmacology, therapeutic use)
- Infant
- Infant, Newborn
- Infusions, Intravenous
- Injections, Subcutaneous
(adverse effects)
- Male
- Radiography
- Recombinant Fusion Proteins
(administration & dosage, pharmacology, therapeutic use)
- Rickets
(diagnostic imaging, drug therapy, etiology)
- Treatment Outcome
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