DENVER, Sept. 14 Enobia Pharma today announced positive data from a clinical study of ENB-0040, a bone targeted enzyme replacement therapy, under investigation for the treatment of hypophosphatasia (HPP). After six months of treatment with ENB-0040, four of five severely affected patients showed marked improvements in bone mineralization, correction of skeletal defects, better respiratory function, including weaning from assisted ventilation, and cognitive and motor development. These findings were presented by Dr. Michael Whyte at the 31(st) Annual Meeting of the American Society for Bone and Mineral Research in Denver, CO.
HPP is a genetic disease characterized primarily by defective bone mineralization and is caused by a deficiency in the enzyme tissue non-specific alkaline phosphatase (TNSALP). This enzyme plays a key role in regulating skeletal mineralization. There are currently no therapies approved for HPP. As an enzyme replacement therapy designed to specifically target TNSALP to the bones, ENB-0040 may help correct the enzyme deficiency and restore bone mineralization.
"Poor bone formation in infants with severe hypophosphatasia has devastating consequences, including fractures, respiratory failure and death in approximately half the infants," stated Michael P. Whyte, M.D., Medical/Scientific Director of the Center for Metabolic Bone Disease and Molecular Research at Shriners Hospitals for Children in St. Louis and an investigator for the study. "The findings from this study are very encouraging, as they demonstrate correction of the primary skeletal disturbance after treatment with ENB-0040."
"The results from this study in infants and young children mark an important milestone for our program," said Hal Landy, M.D., Chief Medical Officer and Vice President, Medical Affairs of Enobia. "We are pleased that all five patients who completed the study have opted to continue treatment under a long-term extension protocol, and we have amended the initial study to include an additional five patients. We will also begin enrollment of a Phase 2 study in children aged five to 12 years in the weeks ahead."
Study Design and Findings
The infant study was designed to assess the safety, tolerability and efficacy of ENB-0040 in infants with HPP. Subjects received an initial intravenous dose of ENB-0040, followed by subcutaneous injections three times weekly for six months.
Three severely affected infants and two young children completed six months of treatment. There were no deaths or drug-related serious adverse events. Subcutaneous dosing was well tolerated, and no anti-ENB-0040 antibodies were detected. At six months, four of five patients with severe rickets treated with ENB-0040 showed marked radiographic, respiratory and functional improvement, while the fifth and most severely affected showed functional improvement and changes in biochemical markers suggesting bone remineralization. Notably, no new fractures were reported.
Hypophosphatasia is a rare, inherited, and sometimes fatal metabolic bone disease. Affected individuals have low levels of the tissue non-specific form of alkaline phosphatase, an essential regulator of bone mineralization, leading to rickets in infants and children and osteomalacia ("soft bones" resulting from poor mineralization) in adults. Disease severity is inversely proportional to the age at symptom onset. Clinical severity ranges from the severe perinatal or infantile forms, with marked skeletal hypomineralization and respiratory compromise often causing death, to a persistent and debilitating osteomalacia in adults.
In the infantile form, infants may appear normal at birth but develop serious symptoms in the first six months of life. These can include failure to thrive, respiratory failure, fractures, and seizures. Radiographic findings include generalized hypomineralization and rickets. First year mortality in these patients is estimated at 50 percent. In the childhood form, patients have varying degrees of skeletal hypomineralization and may have frank rickets, short stature, bone pain, muscle weakness, delayed motor milestones, early loss of deciduous teeth, and may experience frequent, poorly-healing fractures. In the adult form, the underlying osteomalacia causes pathological fractures that impair ambulation.
ENB-0040, an investigational treatment for hypophosphatasia, is a subcutaneous enzyme replacement therapy of tissue non-specific alkaline phosphatase (TNSALP) fused to a patented bone targeting peptide. ENB-0040 is designed to directly target TNSALP to the bone in order to correct the enzyme deficiency, which could lead to restoration of normal bone mineralization. ENB-0040, awarded orphan designation in the US and EU in 2008 and Fast Track status in 2009, is currently in Phase 2 clinical development.
About Enobia Pharma Inc.
Enobia Pharma Inc. is a private, Montreal based company focused on the development of therapeutics to treat serious bone disorders for which there are no drug therapies currently approved. ENB-0040, an investigational drug for the treatment of hypophosphatasia, is the Company's lead program. For more information, please visit www.enobia.com.
SOURCE Enobia Pharma Inc.