ENB-0040 Shows Promise for Hypophosphatasia in Children
Treatment with ENB-0040 linked to healing of rickets, improved pulmonary and physical function
THURSDAY, March 8 (HealthDay News) -- For infants and children with hypophosphatasia, treatment with ENB-0040, a bone-targeted, recombinant human tissue-nonspecific isozyme of alkaline phosphatase (TNSALP), is associated with healing of rickets and improved pulmonary and physical function, according to an open-label study published in the March 8 issue of the New England Journal of Medicine.
Michael P. Whyte, M.D., from Shriners Hospital for Children in St. Louis, and colleagues enrolled 11 infants and young children with life-threatening or debilitating perinatal or infantile hypophosphatasia in a multinational, open-label study of ENB-0040 treatment. Ten of the patients completed six months of treatment and nine completed one year.
The researchers found that, at six months, healing of rickets in nine patients was accompanied by improvement in pulmonary function and developmental milestones. There was a reduction seen in the elevated plasma levels of TNSALP substrates inorganic pyrophosphate and pyridoxal 5′-phosphate. The increases in serum parathyroid hormone, which accompanied skeletal healing, often required dietary supplementation with calcium. No evidence was seen of hypocalcemia, ectopic calcification, or definite treatment-related serious adverse events. In four patients, low titers of anti-ENB-0040 antibodies developed, with no evidence of clinical, biological, or autoimmune abnormalities seen at 48 weeks of treatment.
"Treatment was associated with healing of the skeletal manifestations of hypophosphatasia as well as improved respiratory and motor function," the authors write. "ENB-0040 appears to be a potential enzyme-replacement therapy in patients with life-threatening hypophosphatasia, a metabolic bone disease."
The study was partly funded by Enobia Pharma, which manufactures ENB-0040; several authors disclosed financial relationships with Enobia.