Horizon Pharma Announces Topline Results from Phase 3 Study of ACTIMMUNE in Friedreich's Ataxia

Horizon Pharma plc (NASDAQ:HZNP), a biopharmaceutical company focused on improving patients’ lives by identifying, developing, acquiring and commercializing differentiated and accessible medicines that address unmet medical needs, today announced that the Phase 3 trial, STEADFAST (Safety, Tolerability and Efficacy of ACTIMMUNE Dose Escalation in Friedreich’s Ataxia study), evaluating ACTIMMUNE® (interferon gamma-1b) for the treatment of Friedreich’s ataxia (FA) did not meet its primary endpoint of a statistically significant change from baseline in the modified Friedreich’s Ataxia Rating Scale (FARS‐mNeuro) at 26 weeks versus treatment with placebo.  FARS‐mNeuro is an exam-based rating scale that measures disease progression based on functional parameters such as speech, ability to swallow, upper and lower limb coordination, gait and posture.
In addition, the secondary endpoints did not meet statistical significance.  No new safety findings were identified on initial review of data other than those already noted in the ACTIMMUNE prescribing information for approved indications.  The Company, in conjunction with the independent Data Safety Monitoring Board, the principal investigator and the Friedreich’s Ataxia Research Alliance (FARA) Collaborative Clinical Research Network (CCRN) in FA, has determined that, based on the trial results, the FA development program will be discontinued, including the 26-week extension study and the long-term safety study.Patients participating in the ongoing extension studies should contact their study site coordinator for further information and next steps.The Company will continue to work with FARA and the principal investigator to further analyze the data to help inform future research efforts as well as future data presentation or publication.
“A well-designed, rigorous study like STEADFAST would not have been possible without the extraordinary drive of the FA community, particularly the people who enrolled in the study, the clinical trial investigators and the Friedreich’s Ataxia Research Alliance,” said Timothy P. Walbert, chairman, president and chief executive officer, Horizon Pharma plc.  “While the results were not what we hoped for, this is the very reason why research and development is important – to find answers that may help inform future research.”
“FARA’s mission is to drive research to develop therapies that will treat and cure Friedreich’s ataxia and we remain passionately committed to that mission so that one day soon patients and caregivers impacted by this devastating disease will have effective treatment options,” said Ronald J. Bartek, co-founder and founding president, FARA.  “We want to extend our sincere appreciation to all of the patients, patient families and investigators who were a part of this study as well as Horizon for collaborating with us so impressively on this important research.”
The announcement today does not impact Horizon Pharma’s full-year 2016 adjusted net sales or adjusted EBITDA guidance, and the Company believes it is well-positioned for growth in 2017 and beyond based on its existing portfolio of medicines.  Horizon’s management will host a live conference call and webcast at 8 a.m. ET to discuss the results of the STEADFAST study.  Conference call details are:
U.S. telephone:  1-888-338-8373 (U.S.)
International telephone:  973-872-3000
Conference ID number:  35706781The live webcast and a replay may be accessed by visiting Horizon’s website at https://ir.horizon-pharma.com.  Please connect to the Company’s website at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast.
About STEADFAST
Conducted by Horizon in partnership with the Friedrich’s Ataxia Research Alliance (FARA), STEADFAST or Safety, Tolerability and Efficacy of ACTIMMUNE Dose Escalation in Friedreich’s Ataxia study enrolled 92 patients at four top FA centers across the country.  The randomized, multi-center, double-blind, placebo-controlled Phase 3 study, evaluated patients treated with subcutaneous doses of either ACTIMMUNE or placebo three times a week for a total of 26 weeks.
The primary endpoint evaluated the effect of ACTIMMUNE versus placebo on the change from baseline to Week 26 in neurological outcome as measured by the modified Friedreich’s Ataxia Rating Scale (FARS‐mNeuro), a subset of the total FARS score that measures objective components of a patient’s ability to function such as upper and lower extremity coordination.  The FARS is a validated neurological outcome scale, in which higher scores reflect a greater level of disability.  FARS-mNeuro was determined by experts in the field to be the most clinically relevant instrument for assessing the effects of treatment on FA in this particular trial.  Secondary endpoints included observed mean change from baseline to week 26 in Activities of Daily Living (ADL), Timed 25-foot Walk Test (T25FW), Friedreich’s Ataxia Rating Scale (FARS) scores, and other neurologic evaluations. In addition to safety and efficacy, the STEADFAST trial evaluated the pharmacokinetic characteristics of ACTIMMUNE in people with FA.
About Friedreich’s ataxia (FA)
FA is a debilitating, life-shortening and degenerative neuro-muscular disorder that affects approximately 4,000 to 6,000 people in the United States.  Onset of symptoms can vary from five years old to adulthood, with the childhood onset tending to be associated with a more rapid progression.  Symptoms include progressive loss of strength and coordination usually leading to wheelchair use; diminished vision, hearing and speech; scoliosis (curvature of the spine); increased risk of diabetes; and a life-threatening heart condition.  Most young people diagnosed with FA require mobility aids such as a cane, walker or wheelchair by their teens or early 20’s.  There are currently no approved treatments for FA.
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 for reducing 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 for delaying time to disease progression for patients with severe, malignant osteopetrosis (SMO), a genetic disorder that affects normal bone formation.  For more information, please see www.ACTIMMUNE.com.
ACTIMMUNE is not indicated for FA.
ACTIMMUNE Important Safety Information 
ACTIMMUNE is contraindicated in patients who develop or have known hypersensitivity to interferon-gamma, E coli-derived products or any component of the product
ACTIMMUNE should be used with caution in patients with:

• pre-existing cardiac conditions, including ischemia, congestive heart failure or arrhythmia
• Seizure disorders or compromised central nervous system function; reduce dose or discontinue
• Myelosuppression, or receiving other potentially myelosuppressive agents; consider dose reduction or discontinuation of therapy
• Severe renal insufficiency
• Age < 1 year

Monitoring:

• Patients begun on ACTIMMUNE before age 1 year should receive monthly assessments of liver function.  If severe hepatic enzyme elevations develop, ACTIMMUNE dosage should be modified
• Monitor renal function regularly when administering ACTIMMUNE in patients with severe renal insufficiency; accumulation of interferon gamma-1b may occur with repeated administration. Renal toxicity has been reported in patients receiving ACTIMMUNE

Pregnancy, Lactation, and Fertility:

• ACTIMMUNE should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus
• Use of ACTIMMUNE by lactating mothers is not recommended. ACTIMMUNE or nursing should be discontinued dependent on the importance of the drug to the mother
• Long-term effects of ACTIMMUNE on fertility are not known

Drug Interactions:

• Concomitant use of drugs with neurotoxic, hematotoxic or cardiotoxic effects may increase the toxicity of interferons
• Avoid simultaneous administration of ACTIMMUNE with other heterologous serum protein or immunological preparations (e.g., vaccines)

Adverse Reactions:

• The most common adverse experiences occurring with ACTIMMUNE therapy are “flu-like” symptoms such as fever, headache, chills, myalgia or fatigue, which may decrease in severity as treatment continues, and may be minimized by bedtime administration of ACTIMMUNE
• Acetaminophen may be used to prevent or partially alleviate the fever and headache
• Isolated cases of acute serious hypersensitivity reactions have been observed in patients receiving ACTIMMUNE
• Reversible neutropenia, thrombocytopenia, and elevations of AST and/or ALT have been observed during ACTIMMUNE therapy
• At doses 10 times greater than the weekly recommended dose, ACTIMMUNE may exacerbate pre-existing cardiac conditions or may cause reversible neurological effects such as decreased mental status, gait disturbance and dizziness

Visit www.ACTIMMUNE.com to download a copy of the ACTIMMUNE Full Prescribing Information.
About Horizon Pharma plc
Horizon Pharma plc is a biopharmaceutical company focused on improving patients’ lives by identifying, developing, acquiring and commercializing differentiated and accessible medicines that address unmet medical needs.  The Company markets 11 medicines through its orphan, rheumatology and primary care business units.  For more information, please visit www.horizonpharma.com.  Follow @HZNPplc on Twitter or view careers on our LinkedIn page.
Forward-Looking Statements
This press release contains forward-looking statements, including statements regarding the planned discontinuation of the FA development program and potential growth of Horizon Pharma’s business.  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 the process and time to wind-down clinical trial programs, and Horizon Pharma’s ability to grow sales and revenues from its existing products and execute on its business strategy.  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.
Contacts: Investors: Tina Ventura Senior Vice President, Investor Relations Investor-relations@horizonpharma.com U.S. Media Contacts: Geoff Curtis Senior Vice President, Corporate Communications media@horizonpharma.com Matt Flesch Executive Director, Product Communications media@horizonpharma.com