SOURCE: Horizon Pharma plc

Horizon Pharma plc

March 07, 2015 15:30 ET

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

SAN DIEGO, CA--(Marketwired - Mar 7, 2015) - 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."

About ACTIMMUNE®
ACTIMMUNE (interferon gamma-1b) is a biologically manufactured protein similar to one the body makes naturally to help prevent infection. ACTIMMUNE is currently approved by the U.S. Food and Drug Administration (FDA) for use in two rare diseases. It is indicated to reduce the frequency and severity of serious infections associated with Chronic Granulomatous Disease (CGD), a genetic disorder that affects the functioning of some cells of the immune system. In addition, ACTIMMUNE is indicated to slow the worsening of severe, malignant osteopetrosis (SMO), a genetic disorder that affects normal bone formation. For more information, please see www.ACTIMMUNE.com.

IMPORTANT SAFETY INFORMATION

APPROVED USES FOR ACTIMMUNE (interferon gamma 1-b)

Chronic Granulomatous Disease (CGD)
ACTIMMUNE is indicated to reduce the frequency and severity of serious infections associated with Chronic Granulomatous Disease. CGD is a genetic disorder that affects the functioning of some cells of the immune system.

Severe, Malignant Osteopetrosis (SMO)
ACTIMMUNE is indicated to slow the worsening of severe, malignant osteopetrosis. SMO is a genetic disorder that affects normal bone formation.

IMPORTANT SAFETY INFORMATION (ISI)

The most common side effects with ACTIMMUNE are "flu-like" symptoms such as fever, headache, chills, myalgia (muscle pain) or fatigue, which may decrease in severity as treatment continues. Bedtime administration of ACTIMMUNE may minimize some of these symptoms. Acetaminophen may be helpful in preventing fever and headache.

If you are pregnant or plan to become pregnant or plan to nurse you should consult your physician.

ACTIMMUNE can cause severe allergic reactions and/or rash. Do not use ACTIMMUNE if you are allergic to interferon-gamma, E. coli-derived products or any component of the product (See Full Prescribing Information for a list of components). If you develop a serious reaction to ACTIMMUNE, discontinue it immediately and contact your doctor or seek medical help.

At high doses, ACTIMMUNE can cause (flu-like) symptoms, which may worsen some pre-existing heart conditions. Tell your doctor if you have a cardiac condition, such as irregular heartbeat, heart failure or decreased blood flow to your heart.

ACTIMMUNE may cause reversible changes to your nervous system, including decreased mental status, walking disturbances and dizziness. Tell your doctor if you have a history of seizures or other neurologic disorders.

Bone marrow function may be suppressed with ACTIMMUNE and decreased production of cells important to the body may occur. This effect, which can be severe, is usually reversible when the drug is discontinued or the dose is reduced. Tell your doctor if you have, or have had, reduced bone marrow function. Your doctor will monitor these cells with blood tests at the beginning of therapy and at 3 month intervals thereafter.

Taking ACTIMMUNE may cause reversible changes to your liver function, particularly in patients less than one year old. Your doctor will monitor your liver function with blood tests at the beginning of therapy and at 3 month intervals. If the patient is 1 year or less, monitoring will be done on a monthly basis.

If you are receiving ACTIMMUNE at home, your doctor will provide to you or your caregiver appropriate instructions on the administration of the drug and disposal of the container, needles and syringes.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

This information is not intended to replace discussions with your doctor. For additional information about ACTIMMUNE, please consult the Full Prescribing Information and the Information for the Patient/Caregiver and talk to your doctor. ACTIMMUNE is available by prescription only.

Visit www.ACTIMMUNE.com to download a copy of the ACTIMMUNE Full Prescribing Information.

About Horizon Pharma plc
Horizon Pharma plc is a specialty biopharmaceutical company focused on improving patients' lives by identifying, developing, acquiring and commercializing differentiated products that address unmet medical needs. The company markets a portfolio of products in arthritis, inflammation and orphan diseases. The company's U.S. marketed products are ACTIMMUNE® (interferon gamma-1b), DUEXIS® (ibuprofen/famotidine), PENNSAID® (diclofenac sodium topical solution) 2% w/w, RAYOS® (prednisone) delayed-release tablets and VIMOVO® (naproxen/esomeprazole magnesium). Horizon's global headquarters are in Dublin, Ireland. For more information, please visit www.horizonpharma.com.

Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding potential clinical trials evaluating interferon gamma-1b treatment in Autosomal Dominant Osteopetrosis Type II patients and Horizon's plans to further explore the clinical utility of ACTIMMUNE. Forward-looking statements speak only as of the date of this press release and Horizon does not undertake any obligation to update or revise these statements, except as may be required by law. These forward-looking statements are based on management's expectations and assumptions as of the date of this press release and actual results may differ materially from those in these forward-looking statements as a result of various factors. These factors include, but are not limited to, risks regarding whether results of subsequent studies will be consistent with results of pre-clinical studies, whether Horizon will seek to conduct further studies of ACTIMMUNE or have the financial resources to do so, and the risks associated with pre-clinical and clinical development of drug candidates. For a further description of these and other risks facing Horizon, please see the risk factors described in Horizon's filings with the United States Securities and Exchange Commission, including those factors discussed under the caption "Risk Factors" in those filings. Forward-looking statements speak only as of the date of this press release and Horizon undertakes no obligation to update or revise these statements, except as may be required by law.

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