Shriners Hospitals for Children's Dr. Michael Whyte Presents First
Efficacy and Safety Results of Targeted Enzyme Replacement Therapy
in Patients With Rare Genetic Bone Disease
Data Presented at The Endocrine Society 2009 Meeting
in Washington, D.C.
ST. LOUIS, June 11, 2009 (GLOBE NEWSWIRE) -- A new experimental targeted enzyme replacement therapy strengthens the bones of infants with a severe, sometimes deadly, genetic bone disorder known as hypophosphatasia (HPP), according to early clinical data presented by Michael P. Whyte, M.D., medical/scientific director of the center for metabolic bone disease and molecular research at Shriners Hospitals for Children - St. Louis.
"There is an urgent need for an effective treatment for these infants whose bones are so brittle that their rib cages often break just from breathing; about half of the babies with the severe infantile form of hypophosphatasia will die before their first birthday," Dr. Whyte said. "Without any approved treatments, we currently can only try to manage symptoms of hypophosphatasia without addressing the underlying problem - a profound lack of bone mineralization. This is the first time we've seen a drug therapy positively impact bone formation in these severely sick infant patients."
Dr. Whyte presented the results of a Phase I safety trial of the experimental treatment - currently known as ENB-0040 - in adults, and early safety and efficacy findings from an ongoing study in severely affected infants at The Endocrine Society's 91st Annual Meeting (the ENDO 09 Conference) today in Washington, D.C. There were no drug-related serious adverse events reported in either study, nor did any of the patients develop anti-ENB-0040 antibodies.
Patients with HPP lack an enzyme called tissue non-specific alkaline phosphatase (TNSALP) that plays a key role in bone formation. ENB-0040 is an enzyme replacement therapy designed to specifically target TNSALP to the bones, with the goal of "normalizing" bone mineralization.
In the infant trial, all patients had undermineralized "soft" and deformed bones (rickets) when they entered the study. After an initial single intravenous dose, the patients received thrice-weekly subcutaneous doses of ENB-0040 for up to six months.
So far, X-rays at three months showed substantial new mineralization in the ribs, wrists, knees and long bones in the first three of five patients. The patients' overall clinical status improved as well, with most showing improved growth and requiring less respiratory support over the course of treatment.
Enobia Pharma, the Montreal, Canada-based company developing ENB-0040, sponsored both studies.
Additional Phase II clinical trials are planned for children and adults with HPP during 2009 (www.clinicaltrials.gov).
About Shriners Hospitals for Children
Shriners Hospitals for Children is an international health care system dedicated to providing pediatric specialty care, innovative research and outstanding teaching programs. Children up to age 18 with orthopaedic conditions, burns, spinal cord injuries, and cleft lip and palate are eligible for care and receive all services with no financial obligation to the patients or their families. For more information about Shriners Hospitals for Children, please visit www.shrinershospitals.org.
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, but morbidity can be cumulative and can worsen with age. Clinical severity ranges from the severe perinatal or infantile forms, with profound skeletal hypomineralization and respiratory compromise often causing death, to 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 percent. 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. Childhood patients may also experience poorly-healing fractures. In the adult form, the underlying osteomalacia causes pathological fractures that in some cases stops ambulation.
About ENB-0040
ENB-0040 is a subcutaneous enzyme replacement therapy of tissue non-specific alkaline phosphatase (TNSALP) fused to a patented bone targeting peptide. Preclinical studies in the "knockout" mouse model of severe hypophosphatasia showed that subcutaneous administration of ENB-0040 significantly improved survival, prevented the skeletal manifestations of the disease and corrected skeletal defects in mice with established disease. ENB-0040, awarded orphan designation in the US and EU in 2008 and Fast Track status in 2009, is currently in phase II testing.