Why is there a need for new osteoarthritis treatments?
Osteoarthritis (OA) is one of the most common causes of disability, and inadequate pain control can lead to joint stiffness that may impair mobility for patients.
Since OA is a chronic condition, patients are often treated with nonsteroidal anti-inflammatory drugs (NSAIDs) to manage their pain for an extended period of time.
Although effective, NSAIDs have been associated with significant safety concerns, including cardiovascular thrombotic events, myocardial infarction, stroke, gastrointestinal ulcers and bleeding, and renal events such as acute renal failure.
The risk of serious adverse events is higher among patients receiving higher doses of NSAIDs. As such, health authorities in the U.S. and EU and professional medical organizations including the American Heart Association, American Gastroenterological Association and The American College of Rheumatology recommend that NSAIDs be used at the lowest effective dose for the shortest possible duration consistent with individual patient treatment goals.
Due to these serious, dose-related safety concerns associated with NSAID use, there is great need for new therapeutics that can provide pain relief at low doses.
Please can you outline the Phase 3 results Iroko Pharmaceuticals recently announced at the 2014 European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology?
The Phase 3 study enrolled adult patients with clinical and radiographic evidence of OA of the hip or knee (Kellgren-Lawrence 2-3), who required chronic acetaminophen or NSAID therapy.
Patients who demonstrated significant pain following discontinuation of these agents were randomized to receive investigational low dose SoluMatrix® meloxicam 5 mg or 10 mg once daily or placebo.
OA patients, who received SoluMatrix® meloxicam 5 mg and 10 mg, reported significantly greater pain relief over 12 weeks compared with the placebo control group. SoluMatrix® meloxicam was evaluated at doses that are 30 percent lower than currently available meloxicam products.
How did the reported pain relief compare to placebo?
At week 12, patients treated with SoluMatrix® meloxicam 5 mg (P = 0.0005) and 10 mg (P = 0.0059) achieved significant pain relief as measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale compared with placebo.
Based on the Patients’ Global Impression of Change (PGIC), significantly more patients reported their condition as “very much improved” or “much improved” versus “much worse” or “very much worse” following SoluMatrix® meloxicam 5 mg (P = 0.0049) or 10 mg (P = 0.0012) treatment compared with the placebo control group.
Additionally, patients in the SoluMatrix® meloxicam 5 mg (P = 0.006) and 10 mg (P = 0.0013) treatment groups used significantly less rescue medication (acetaminophen) compared with patients in the placebo group.
What were the most frequently reported adverse events?
Adverse events reported in the study were comparable to those reported with the use of currently available meloxicam products.
The most frequently reported adverse events (occurring in >2 percent of patients) in patients in the combined SoluMatrix® meloxicam treatment group were diarrhea, headache and nausea. No deaths or serious adverse events were reported.
What further evaluation do you have planned?
We plan on completing the analysis of this pivotal Phase 3 study and will submit a New Drug Application in the U.S. for SoluMatrix® meloxicam by January 2015. A second Phase 3 study evaluating the safety of long term treatment is ongoing.
What do you think the future holds for pain control in osteoarthritis patients?
There is an unmet need for effective pain treatment options that can be given at low doses to potentially reduce the risk of treatment-related adverse events.
Iroko is at the forefront of developing several novel SoluMatrix® NSAIDs that are designed to provide effective pain relief at lower doses than existing commercially available oral formulations while reducing the amount of medication in the patient’s bloodstream.
This approach is consistent with guidance for physicians whose patients may require NSAID treatment for extended periods of time to manage chronic conditions such as OA.
What are Iroko Pharmaceuticals plans for the future?
As an indication of our commitment to making new analgesic options available to patients, we have initiated clinical studies with other NSAIDs with optimized absorption properties to address unmet needs in pain management.
Iroko’s low dose NSAID portfolio now contains two FDA-approved NSAIDs, ZORVOLEX® and TIVORBEXTM for treatment of mild to moderate pain in adults. We are currently studying four other low dose NSAIDs using SoluMatrix Fine Particle TechnologyTM in adults with OA pain, two of which are in late-stage development.
Looking ahead, approval by the U.S. Food and Drug Administration (FDA) of a supplemental indication for ZORVOLEX (diclofenac) capsules for treatment of OA pain is expected later in 2014.
Where can readers find more information?
For more information, visit Iroko Pharmaceuticals LLC.
About Dr. Young and John Vavricka
John Vavricka brings to Iroko over 20 years of broad international experience in the pharmaceutical industry and a demonstrated capacity to build high-performing organizations.
Since John became the founding CEO of Iroko in 2007, the company has assembled a workforce led by a seasoned management team, acquired several prescription pharmaceuticals, established sales and distribution networks in more than 40 countries, and created an R&D portfolio of seven development programs in mid-to-late-phase clinical studies.
Most recently, John has been leading Iroko’s initiative to become a leading pain-medicine company both by expanding its base business and applying new technologies to established products to enhance their benefits. The company is an industry leader using nanotechnology to develop new formulations of NSAIDs, one of the largest classes of pain medicines.
Dr. Clarence Young has more than 25 years of drug development and research experience in the pharmaceutical industry, as well as in academia. Over the course of his career, he has provided medical oversight of numerous clinical trials, regulatory filings, and product launches. Prior to joining Iroko, he was Vice President, Targeted Therapies and Integrated Hospital Care, at Novartis Pharmaceuticals Corporation, responsible for leading cross-functional teams in development, global registration, and commercialization of small and large molecules.
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