Horizon Pharma plc Announces That Pre-Clinical Data Show Treatment With Interferon Gamma Improved Signs of Disease Severity of Rare Bone Disease

Horizon Pharma plc (NASDAQ: HZNP), a specialty biopharmaceutical company focused on improving patients' lives by identifying, developing, acquiring and commercializing differentiated products that address unmet medical needs, today announced that pre-clinical data from an investigator initiated study demonstrated that treatment with murine interferon gamma, which is an analogue of interferon gamma-1b (ACTIMMUNE®), improved the signs of disease severity in a mouse model of Autosomal Dominant Osteopetrosis Type II (ADO2). The data were presented at The Endocrine Society's 97th Annual Meeting in San Diego.

Osteopetrosis is typically divided into two categories: autosomal recessive osteopetrosis or severe malignant osteopetrosis and autosomal dominant osteopetrosis (further divided into Type I and II (ADO2)). ADO2 is a rare, inherited disease resulting from a gene mutation that, despite an increased bone mass, is characterized by a wide range of symptoms and severity including multiple fractures, impaired vision and osteomyelitis (bone infection). ADO2 is the most common type of Autosomal Dominant Osteopetrosis with an estimated prevalence of up to 5.5 per 100,000.

"This disease has limited treatment options and as reflected in this study, treatment with calcitriol has not resulted in much clinical improvement," said Dr. Michael J. Econs, professor of medicine, Glenn W. Irwin, Jr., professor in endocrinology and metabolism, Indiana University School of Medicine. "I'm hopeful that these pre-clinical data with this analogue will lead to a clinical trial evaluating interferon gamma-1b treatment in Autosomal Dominant Osteopetrosis Type II patients."

The pre-clinical study evaluated the effect of murine interferon gamma in a knock-in mouse model of the p.G213R mutation in the murine CLCN7 gene that results in severe osteopetrosis and death in homozygous (identical gene pairs) mice and a moderately severe form of osteopetrosis in heterozygous (different gene pairs) mice. Mice (n=10/group) were administered either placebo or varying doses (low, medium, high) of interferon gamma or calcitriol (a form of vitamin D) five times per week for 8 weeks.

At the end of the eight-week treatment, X-ray and microcomputed tomography showed that treatment with interferon gamma significantly (p < 0.005) reduced the increase of whole body areal bone mineral density, an important measure of bone strength, across all dosing regimens in both male and female ADO2 mice compared to the vehicle group.

Additionally, interferon gamma treatment significantly reduced (p < 0.05) the bone volume over tissue volume gain across all dosing regimens in both male and female ADO2 mice compared to the vehicle group. In contrast, mice treated with low and medium doses of calcitriol showed a trend of higher bone mass including whole body areal bone mineral density and bone volume over tissue volume gain whereas the high dose calcitriol group significantly increased areal bone mineral density and bone volume over tissue volume gain compared to the placebo group.

"Autosomal Dominant Osteopetrosis Type II is a devastating disease and while these data are early, the findings may be important in exploring future treatment," said Jeffrey W. Sherman, chief medical officer and executive vice president, research and development, Horizon Pharma plc. "Today, ACTIMMUNE is approved for severe malignant osteopetrosis, the autosomal recessive form, and often the most severe form of osteopetrosis. Horizon is committed to exploring the full clinical utility of ACTIMMUNE and furthering potential treatment options where unmet needs exist for patients with osteopetrosis."