ZORVOLEX™ (diclofenac) Utilizing SoluMatrix Fine Particle Technology™ Was Well-Tolerated in Treatment of Osteoarthritis Pain

12-week Safety Data from Iroko Pharmaceuticals’ Phase 3 Trial Presented at ACR

SAN DIEGO, OCTOBER 29, 2013 — Iroko Pharmaceuticals, LLC, a global specialty pharmaceutical company dedicated to advancing the science of analgesia, today presented Phase 3 results from a study of ZORVOLEX™ (diclofenac) capsules in patients with osteoarthritis pain. Taken over a period of twelve weeks, there were no ZORVOLEX™- related serious gastrointestinal, renal or cardiovascular (myocardial infarction or stroke) adverse events,1 which are all risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs). 2,3,4,5 These data were presented at the 2013 American College of Rheumatology (ACR) Annual Scientific Meeting in San Diego. ZORVOLEX is now approved by the U.S. Food and Drug Administration (FDA) for the treatment of mild to moderate acute pain in adults and is under investigation for the treatment of osteoarthritis pain.

Osteoarthritis is one of the most commonly treated conditions in the United States6 and patients are often treated with NSAIDs7 to manage their pain for an extended period of time.8

“The primary goal of the Iroko clinical development program is to identify treatment options that potentially address the dose- and duration-related adverse events that accompany traditional NSAIDs,” said Dr. Clarence Young, MD, Chief Medical Officer of Iroko Pharmaceuticals. “We are encouraged by these findings as they suggest that ZORVOLEX may be an effective lower-dose option for the treatment of osteoarthritis pain.”

In a multicenter, double-blind, parallel-group study, 305 patients 41 to 90 years of age with osteoarthritis of the hip or knee were randomized to receive ZORVOLEX 35 mg three times daily or 35 mg twice daily, or placebo.1 The primary endpoint was the mean change from baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC®) pain subscale at week 12. Safety and tolerability were also assessed.1 Primary efficacy results were presented earlier this year at the 2013 World Congress on Osteoarthritis, held April 18-21 in Philadelphia.

The most frequently reported adverse events in the study (> 3 percent in any treatment group) were generally similar across treatment groups, and included diarrhea, headache, nausea, and upper respiratory tract infection. No serious gastrointestinal bleeds, cardiovascular (myocardial infarction or stroke) or renal adverse events occurred in any treatment group. The most frequent (≥ 1 percent in any treatment group) adverse events causing patients to withdraw from the study included diarrhea, upper abdominal pain, and alanine aminotransferase elevation.1

About Iroko’s Lower Dose NSAID Portfolio

The risk of serious adverse events, including cardiovascular thrombotic events, myocardial infarction, stroke, gastrointestinal ulcers, gastrointestinal bleeds,3 and renal events such as acute renal failure4 associated with NSAIDs is higher among patients receiving higher doses.5 Iroko is at the forefront of the development of lower dose NSAIDs—new low dose medicines based on existing NSAIDs—using iCeutica Pty Ltd’s proprietary SoluMatrix Fine Particle Technology™ exclusively licensed to Iroko for use in NSAIDs. For more information see www.iroko.com.

About ZORVOLEX

ZORVOLEX was approved by the U.S. Food and Drug Administration (FDA) in October 2013 for the treatment of mild to moderate acute pain in adults1. It is the first and only FDA-approved NSAID developed using proprietary SoluMatrix Fine Particle Technology™. ZORVOLEX was developed to address FDA’s public health advisory recommending that NSAIDs be used at the lowest effective dose for the shortest duration of time consistent with individual patient treatment goals.9 For more information, see ZORVOLEX.com.

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 higher than users of either drug alone.

Most common adverse reactions in clinical trials (incidence ≥2%) include: edema, nausea, headache, dizziness, vomiting, constipation, pruritus, flatulence, pain in extremity, 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 Information for additional important safety and dosing information.

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. In addition to the Iroko products that are marketed worldwide, the company has a robust pipeline of investigational lower dose NSAID products being developed using iCeutica Pty Ltd’s proprietary SoluMatrix Fine Particle Technology™. For more information, visit www.iroko.com.

Media Contact: Jessica Donnelly for Iroko Pharmaceuticals, LLC, 212-798-9819

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

 

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1 Safety of Lower-Dose Diclofenac Submicron Particle Capsules Dosed Up To 12 Weeks in Patients with Osteoarthritis. Poster at ACR.

2 ZORVOLEX Prescribing Information

3 Rahme E et. al. (2001 Aug). Cost of prescribed NSAID-related gastrointestinal adverse events in elderly patients. Br J Clin Pharmacol. 52(2): 185-192.

4 Annual Review of Medicine, Nonsteroidal Antiinflammatory Drugs and Renal Function. Vol. 35: 411-428. DOI: 10.1146/annurev.med.35.020184.002211.

5 Risser A. (2009 Dec). NSAID Prescribing Precautions. Am Fam Physician. 80(12):1371-1378.

6 NSAIDs: Optimizing Pain Management Through Risk Reduction. The American Journal of Managed Health. Vol. 19, No 14

7 D.L. Scott et. al. (2000) The Long-Term Effects of Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis of the Knee: A Randomized, Placebo-Controlled Trial. Rheumatology. 39: 1095-1101

8 Anthony D. Woolf et. al. Burden of Major Musculoskeletal Conditions. World Health Organization. Available at http://www.who.int/bulletin/volumes/81/9/Woolf.pdf

9 U.S. Food and Drug Administration. Public Health Advisory – FDA Announces Important Changes and Additional Warnings for COX-2 Selective and Non-Selective Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).