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Enobia Reports Positive Results For Phase II Trial of ENB-0040 in Juvenile Hypophosphatasia

PRAGUE, Sept. 24 /PRNewswire/ -- Enobia Pharma today announced positive results for its Phase II juvenile clinical trial of ENB-0040 (asfotase alfa), an experimental bone-targeted enzyme replacement therapy intended for the treatment of hypophosphatasia (HPP).  Hypophosphatasia is a rare, inherited, and sometimes fatal metabolic bone disease that affects individuals of all ages. Michael Whyte, MD, Medical/Scientific Director of the Center for Metabolic Bone Disease and Molecular Research at Shriners Hospital for Children in St. Louis, Missouri, and a principal investigator of the Phase II study, presented the findings at the European Society for Paediatric Endocrinology (ESPE) Annual Meeting in Prague. Enobia's abstract describing these Phase II results was awarded the Henning Anderson Prize for best clinical abstract by ESPE.

In this trial, after six months of ENB-0040 treatment results include:

  • Radiographic improvement of rickets
  • Improvement in muscle strength and agility over baseline, including an average improvement of 125m on six-minute walk test
  • Amelioration of pain in 6 of 7 patients experiencing pain at baseline  

"We are encouraged by these preliminary results. Improvements were seen in objective measures of muscle strength, agility and pain. These were accompanied by histomorphometric, radiologic and biomarker improvements, suggesting an integrated improvement of this debilitating skeletal disorder," said Hal Landy, MD, Chief Medical Officer at Enobia. "With nearly 50 patients on ENB-0040 treatment, we are rapidly expanding our understanding of the potential safety and efficacy of ENB-0040."  

Dr. Michael Whyte, Medical/Scientific Director of the Center for Metabolic Bone Disease and Molecular Research at Shriners Hospital for Children in St. Louis and a Principal Investigators said, "The findings from this study represent an important advance in our quest to find a medical treatment for hypophosphatasia."

ENB-0040 Phase II Juvenile Trial Design

This six-month, Phase II, multinational, open-label investigation of the safety, tolerability, pharmacokinetics (PK), and efficacy of ENB-0040 treatment enrolled 13 children (ages 5-12 years, Tanner Stage less than or equal to 2) with rickets and gross motor deficits from HPP. One patient discontinued the trial due to elective scoliosis surgery. Inclusion criteria included low serum ALP activity for age, plasma PLP greater than or equal to 2x normal range, normal serum vitamin D, and evidence of HPP associated rickets on radiographs. Exclusion criteria included significant co-morbid disease, nutritional rickets, bisphosphonate exposure, hypocalcemia or hypophosphatemia, or experimental treatment for HPP (e.g., bone marrow transplantation). All patients who have completed the 6 month study have been enrolled in an extension study.

ENB-0040 Phase II Juvenile Trial Results

Although radiographs have yet to be assessed by blinded radiologists and compared to historical controls, preliminary radiographic improvements in rickets were noted in all patients by investigators. Consistent with data from the infant study, radiographic improvement was noted as early as 6 weeks after starting treatment in some patients. Plasma levels of two naturally occurring substrates of alkaline phosphatase, PLP and PPI, declined following subcutaneous (SC) injection of ENB-0040. Serum ALP concentrations increased substantially and were maintained within the target range throughout the study. Positive skeletal mineral balance with healing rickets was heralded by increases in serum parathyroid hormone levels. There were no overt episodes of hypocalcemia from "hungry bones."

SC injections of ENB-0040 were generally well tolerated and no serious adverse events were reported. Injection site reactions consisting of transient skin discoloration were common. Retinal findings, renal ultrasound studies, and skin examination showed no evidence of ectopic mineralization.

Enobia recently reported that updated results from a phase I/II trial in infantile HPP will be presented at the 60th Annual American Society of Human Genetics Annual Meeting in Washington, DC on November 3. In addition, a third phase II trial of ENB-0040 in adolescents and adults with HPP is underway.  

About Hypophosphatasia

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 and includes marked skeletal hypomineralization. The marked skeletal hypomineralization causes respiratory compromise often resulting in death in infants and persistent and debilitating osteomalacia in children and 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 often with debilitating bone pain.

About ENB-0040

There are currently no therapies approved for HPP, a rare genetic disease characterized primarily by defective bone mineralization caused by a deficiency in the enzyme tissue non-specific alkaline phosphatase (TNSALP). ENB-0040 (asfotase alfa), an investigational treatment for hypophosphatasia, is a subcutaneous enzyme replacement therapy of tissue non-specific alkaline phosphatase (TNSALP) fused to a 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 U.S. and EU in 2008 and Fast Track status in 2009, is currently in Phase 2b 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

SOURCE Enobia Pharma Inc.
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