Enobia Pharma Initiates Clinical Testing of Enzyme Replacement Therapy to Treat Hypophosphatasia
MONTREAL, Aug. 20 /PRNewswire/ — Enobia Pharma, an emerging biotech company focused on developing novel therapeutics for serious bone disorders, today announced that the first patient in its clinical program for hypophosphatasia has been dosed. Enobia is investigating Enzyme Replacement Therapy (ERT) with ENB-0040 for the treatment of this rare and often crippling genetic bone disorder for which there is no approved treatment.
Under two separate protocols, ENB-0040 will be evaluated in both adults and infants afflicted with hypophosphatasia in Canada and the USA. “This may well be a milestone in the treatment of hypophosphatasia,” said Michael Whyte, MD, Professor of Medicine at Washington University School of Medicine, St. Louis, MO, and consultant to Enobia Pharma. “Studies in a mouse model for hypophosphatasia show ENB-0040 has the potential to greatly enhance the quality-of-life for patients.”
Under the first protocol, safety, tolerability and pharmacokinetics of ENB-0040 will be evaluated for one month in an open-label, dose escalation Phase I study of ENB-0040 delivered intravenously and subcutaneously to six adults with hypophosphatasia at three North American sites.
Under the second protocol, safety, tolerability, pharmacokinetics, and efficacy of ENB-0040 will also be evaluated in a six-month open label study of up to six infants with particularly severe hypophosphatasia. Key efficacy outcomes include assessment of skeletal and respiratory manifestations of the disease.
“In preclinical studies using a mouse model, ENB-0040 consistently improved survival as well as bone and dental manifestations of hypophosphatasia. The initiation of clinical studies brings us closer to the goal of providing drug therapy for hypophosphatasia patients where none currently exists,” stated Robert Heft, PhD, Chief Executive Officer of Enobia.
Hypophosphatasia is a rare, inherited, and sometimes fatal metabolic bone disease. Patients have low levels of the tissue non-specific form of alkaline phosphatase, an important 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, but morbidity can be cumulative and worsen with age. Clinical severity ranges from the severe perinatal or infantile form, with profound skeletal hypomineralization and respiratory compromise often causing death, to a more slowly progressive 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. Mortality in these patients may be as high as 50%. In the childhood form, patients have varying degrees of hypomineralization, 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 bone pain due to overt or poorly-healing stress fractures that in some cases stops ambulation.
ENB-0040 is a fusion protein that includes the catalytic domain of human tissue non-specific alkaline phosphatase (TNSALP), and a patented peptide used to target the enzyme to bone. Preclinical studies of ENB-0040 in the “knockout” mouse model of severe hypophosphatasia were recently published in the Journal of Bone and Mineral Research [June 2008:23:777-787] and showed that subcutaneous administration of ENB-0040 significantly improved survival and prevented the skeletal and dental manifestations of the disease.
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 is no currently approved drug therapy. Enzyme Replacement Therapy for the treatment of hypophosphatasia is the Company’s lead program. In 2007 Enobia completed a $40M Series B financing lead by OrbiMed Advisors and CTI Life Sciences.
Company Contact: Julie Anne Smith, (514) 596-2901, extension 214
CONTACT: Julie Anne Smith of Enobia Pharma, +1-514-596-2901, ext. 214