MONTREAL, Aug. 20 /CNW Telbec/ - Enobia Pharma, an emerging Canadian
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 is being evaluated in both adults
and infants afflicted with hypophosphatasia in Canada and the USA.
"This is a significant step towards a treatment for hypophosphatasia, an
under-recognized bone disease that can be fatal in infants and cause serious
disability in older patients," said Dr. Cheryl Greenberg, Medical Director,
Child Health Program, Winnipeg Regional Health Authority, and Professor and
Head, Department of Pediatrics & Child Health, University of Manitoba. "We are
delighted to begin testing a potential treatment. I'm particularly grateful to
our Institutional Review Board and Office of Research Services at the
University of Manitoba, as well as the Research Impact Committees of Health
Sciences Centre Winnipeg for their timely and constructive review of our
protocols. This collaboration has allowed us to expeditiously enroll our group
of patients in this clinical trial."
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
"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. The term hypophosphatasia was coined in 1948 by Dr. John Rathburn, a
Toronto pediatrician who was among the earliest clinicians to describe the
disease. In 1955 Dr. Donald Fraser at the University of Toronto identified the
first biomarker (PEA) helpful in diagnosing hypophosphatasia. In 1957
Dr. Fraser introduced the "infantile", "childhood" and "adult" classification
of hypophosphatasia still in use today. Based on his experience over a 10 year
period in Toronto, Dr. Fraser estimated the incidence of the severe forms of
hypophosphatasia to be 1:100,000 in the general population. The highest known
incidence of hypophosphatasia is among the Mennonite Community living in
Manitoba where 1:2500 individuals are born with the disease.
In hypophosphatasia, 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 may stop 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. The 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. In
addition to the ongoing trials, pediatric studies are also being planned. If
interested in learning more, contact
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. Enobia's other investors include: Fonds de solidarité FTQ,
Desjardins Capital régional et coopératif, Lothian Partners 27 (SARL) Sicar,
T2C2/BIO 2000 s.e.c..
For further information:
For further information: Julie Anne Smith, (514) 596-2901, extension