New Long-Term Safety and Quality of Life Data Reported for ZORVOLEX® in Osteoarthritis Patients

Iroko Presents One-Year Open-Label Phase 3 Data of First Low Dose NSAID at ACR 2014

PHILADELPHIA, November 16, 2014 — Iroko Pharmaceuticals, LLC, a global specialty pharmaceutical company dedicated to advancing the science of analgesia, today announced that ZORVOLEX® (diclofenac) capsules was generally well tolerated and improved the health-related quality of life (HRQOL) in patients with osteoarthritis pain, based on a 12-month, open-label Phase 3 study1,2. These data are being presented at the American College of Rheumatology 2014 Annual Meeting, November 14 -19 in Boston. ZORVOLEX, a nonsteroidal anti-inflammatory drug (NSAID), was approved by the United States Food and Drug Administration (FDA) in August 2014 for the management of osteoarthritis pain and in October 2013 for the treatment of mild to moderate acute pain in adults.

“It is important for us to evaluate the safety of new medicines used in patients with osteoarthritis for extended periods, as they often require long-term management,” said Dr. Roy Altman, Professor of Medicine in Rheumatology at UCLA and lead study author.

The 12-month, open-label, multicenter, Phase 3 study evaluated ZORVOLEX in 601 patients with knee or hip osteoarthritis who were chronic NSAID or acetaminophen users. The majority of patients were women (372/601, 61.9%); patients ranged from 40 to 86 years of age; 45 percent of patients were older than 601. Patients initially received ZORVOLEX 35mg twice daily, although the dosing regimen could be increased to three times daily if necessary, and subsequently reduced as needed2.

In the study, 299 (49.8%) patients who initially received ZORVOLEX 35mg twice daily remained at this dosing regimen and 302 (50.2%) patients increased their ZORVOLEX dosage to 35mg three times daily at least once. Twenty percent of patients whose dose was increased from twice daily to three times daily subsequently underwent a dose reduction back to twice daily2.

The majority of adverse events in the study were mild to moderate in severity. The most frequently reported adverse events included upper respiratory tract infection (47/601, 7.8%), headache (46/601, 7.7%) and urinary tract infection (44/601, 7.3%). Myocardial infarction was reported in two patients and was not considered related to study medication. Gastrointestinal ulcer was reported in one patient1. These data provide long-term safety information on the use of ZORVOLEX in patients with osteoarthritis, a condition associated with chronic pain.

ZORVOLEX capsules 35mg twice or three times daily were associated with improved HRQOL in patients with osteoarthritis pain. Patients receiving ZORVOLEX reported clinically meaningful improvement (≥5) in the Physical Component Score across the 52-week dosing period2. The Short Form-36TM (SF-36v2) is a health-related, patient-reported outcomes tool that assesses physical and mental domains.

“These results add to the growing body of knowledge for ZORVOLEX, a low dose treatment option that is now available for the management of osteoarthritis pain,” said Dr. Clarence Young, Chief Medical Officer of Iroko Pharmaceuticals.

About ZORVOLEX

ZORVOLEX was developed to align with recommendations from FDA and several professional medical organizations that NSAIDs be used at the lowest effective dose for the shortest possible duration consistent with individual patient treatment goals. ZORVOLEX is indicated for the management of mild to moderate acute pain and osteoarthritis pain. The dosage for mild to moderate acute pain is 18mg or 35mg orally three times daily. The dosage for osteoarthritis pain is 35mg orally three times daily. ZORVOLEX is the first FDA-approved low dose NSAID developed using proprietary SoluMatrix Fine Particle Technology™ and is now available by prescription. ZORVOLEX contains diclofenac as submicron particles that are approximately 20 times smaller than their original size. The reduction in particle size provides an increased surface area, leading to faster dissolution. In September 2014, ZORVOLEX was shortlisted in the Best New Drug category for the 10th Annual SCRIP Awards, an award which recognizes excellence in pharmaceutical development. For more information, visit www.ZORVOLEX.com.

ZORVOLEX is indicated for the management of mild to moderate acute pain and osteoarthritis pain.

Important Safety Information about ZORVOLEX

Cardiovascular Risk

Nonsteroidal anti-inflammatory drugs (NSAIDs) may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.

ZORVOLEX is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Risk

NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.

ZORVOLEX is contraindicated in patients with: a known hypersensitivity to diclofenac or its inactive ingredients; a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs.

ZORVOLEX should be used at the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

Elevation of one or more liver tests may occur during therapy with ZORVOLEX. Physicians should measure transaminases (ALT and AST) periodically in patients receiving long-term therapy with ZORVOLEX. ZORVOLEX should be discontinued immediately if abnormal liver tests persist or worsen.

NSAIDs, including ZORVOLEX, can lead to the new onset or worsening of existing hypertension, which may contribute to the increased incidence of cardiovascular events. Blood pressure should be monitored closely during treatment with ZORVOLEX. NSAIDs may diminish the antihypertensive activity of thiazides, loop diuretics, ACE inhibitors and angiotensin II antagonists.

Fluid retention and edema have been observed in some patients taking NSAIDs. ZORVOLEX should be used with caution in patients with fluid retention or heart failure.

Long-term administration of NSAIDs can result in renal papillary necrosis and other renal injury. ZORVOLEX should be used with caution in patients at greatest risk of this reaction, including the elderly, those with impaired renal function, heart failure, liver dysfunction, and those taking diuretics and ACE inhibitors. Treatment with ZORVOLEX in patients with advanced renal disease is not recommended.

Anaphylactoid reactions may occur in patients with the aspirin triad or in patients without prior exposure to ZORVOLEX and should be discontinued immediately if an anaphylactoid reaction occurs.

NSAIDs can cause serious skin adverse events such as exfoliative dermatitis, Stevens – Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. ZORVOLEX should be discontinued if rash or other signs of local skin reaction occur.

Starting at 30 weeks’ gestation, ZORVOLEX and other NSAIDs should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur.

Concomitant administration of diclofenac and aspirin or anticoagulants is not generally recommended because of the risk of increased GI bleeding that is higher than in users of either drug alone.

Most common adverse reactions in clinical trials (incidence ≥2%) include: edema, nausea, headache, dizziness, vomiting, constipation, pruritus, diarrhea, flatulence, pain in extremity, abdominal pain, sinusitis, alanine aminotransferase increased, blood creatinine increased, hypertension, and dyspepsia.

ZORVOLEX capsules do not result in an equivalent systemic exposure to diclofenac as other oral formulations. Therefore, do not substitute similar dosing strengths of other diclofenac products for ZORVOLEX.

Please see full Prescribing Informationfor additional important safety and dosing information.

For more information, visit www.ZORVOLEX.com.

About Iroko Pharmaceuticals, LLC

Iroko is a global specialty pharmaceutical company, based in Philadelphia, dedicated to advancing the science of analgesia. The company develops and globally commercializes pharmaceutical products.

Iroko is at the forefront of the development of SoluMatrix® NSAIDs – new low dose drug products based on existing NSAIDs – using iCeutica Inc.’s proprietary SoluMatrix Fine Particle Technology™ exclusively licensed to Iroko for NSAIDs. ZORVOLEX is the first SoluMatrix® NSAID and is available in pharmacies; a second was approved by FDA in February 2014. For more information, visit www.iroko.com.

 

Contacts:

Jessica Donnelly for Iroko Pharmaceuticals, LLC, 212-798-9819

Kate de Santis, Iroko Pharmaceuticals, LLC, 267-546-1682

 

SoluMatrix Fine Particle Technology™ is a trademark of iCeutica Inc., and the technology is licensed to Iroko for exclusive use in NSAIDs.

SoluMatrix® is a trademark of iCeutica Pty Ltd and is licensed to Iroko.

 

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1 Altman, R., et al., Safety of Solumatrix Diclofenac in Adults with Osteoarthritis: Results of a 12-Month, Phase 3 Study. Poster Presentation at American College of Rheumatology (ACR) 2014 Annual Meeting.

2 Strand, V., et al., A Phase 3 Open-Label Trial of Low-Dose Solumatrix Diclofenac in Patients with Osteoarthritis Pain: Impact of Long-Term Administration on Patient-Reported Outcomes. Poster Presentation at American College of Rheumatology (ACR) 2014 Annual Meeting.