Iroko Pharmaceuticals, LLC, a Philadelphia-based pharmaceutical company dedicated to advancing the science of analgesia, has announced the presentation of new data from two Phase 3 studies of its SoluMatrix® nonsteroidal anti-inflammatory drug (NSAID) portfolio. Data presented include results from a study of post-surgical acute pain showing that fewer patients taking TIVORBEX™ (indomethacin) capsules needed additional opioid-containing analgesia compared to placebo over a 48 hour period following surgery.1 Additionally, data from a different study showed that treatment with ZORVOLEX® (diclofenac) capsules resulted in improvement in patient reported outcomes and quality of life measures in individuals with osteoarthritis (OA) of the hip and knee when compared to placebo2.
“As a leader in the pain management space, we are continuing to study the SoluMatrix® NSAIDs in our portfolio to understand how they can better address unmet needs in analgesia,” said John Vavricka, President and CEO of Iroko Pharmaceuticals. “We are encouraged by this new data that demonstrate the real-world application of our low dose NSAIDs in limiting the use of opioids and improving patient-associated measures of pain1,2, two important areas in pain management. These data further establish ZORVOLEX and TIVORBEX as promising therapeutic options.”
ZORVOLEX and TIVORBEX are part of Iroko’s low dose NSAID portfolio created using proprietary SoluMatrix Fine Particle Technology™, which produces NSAIDs 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. Both ZORVOLEX and TIVORBEX were recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of mild to moderate acute pain in adults.3,4 A supplemental New Drug Application (sNDA) for ZORVOLEX for the treatment of osteoarthritis (OA) pain was also accepted for review by FDA in January 2014.
About the Phase 3 Data Evaluating TIVORBEX in Patients with Post-Surgical Acute Pain Results from a pivotal Phase 3 study of TIVORBEX in acute pain will be presented at the American Pain Society’s (APS) 33rd Annual Scientific Meeting, taking place April 30 – May 3 in Tampa, FL. The analysis assessed opioid rescue medication usage in 462 patients, aged 18?”68 years, experiencing significant post-surgical pain, who were randomized to receive TIVORBEX 40 mg three times daily (TID) or twice daily (BID) or 20 mg TID, celecoxib (400 mg loading dose followed by 200 mg BID), or placebo1.
As expected for patients with post-surgical pain of this magnitude, a high proportion of patients in all study arms required additional rescue analgesia, hydrocodone/acetaminophen or oxycodone/acetaminophen, over the 48 hours following randomization.
“Whenever possible, it is important for healthcare providers to avoid prescribing treatments that can be associated with the potential for dependency and diversion,” said Dr. Clarence Young, Chief Medical Officer of Iroko Pharmaceuticals. “Patients treated with TIVORBEX in this study required less opioid rescue medication compared to placebo, suggesting that TIVORBEX is a valuable treatment option for patients with acute pain.”
Results showed the following:1
- About half as many opioid-containing rescue medication tablets were used in the TIVORBEX arms compared to the placebo group over 48 hours. Patients randomized to the 40 mg of TIVORBEX three times daily and twice daily treatment arms used an average of 2.7 tablets of opioid containing analgesics, also referred to as rescue medication; the TIVORBEX 20 mg three times daily group used an average of 3.0 tablets, the celecoxib group used an average of 3.1 tablets, and patients in the placebo group used an average of 5 tablets.
- The time to first use of rescue medication, measured following the start of treatment with either TIVORBEX or placebo, occurred later on average in the TIVORBEX 40 mg three times daily, 40 mg twice daily and celecoxib 200 mg twice daily groups compared with placebo. The difference was statistically significant for the TIVORBEX 40 mg three times daily group (P = 0.008) compared to placebo.
- The most common adverse events in this study (>5%) included nausea, dizziness, and vomiting, and were generally similar across treatment groups.
About the Phase 3 Data Evaluating ZORVOLEX in Patients with Osteoarthritis An analysis of the pivotal Phase 3 ZORVOLEX trial, presented at the 2014 Osteoarthritis Research Society International (OARSI) World Congress, which took place April 24 – April 27 in Paris, France, assessed a number of patient reported outcomes and quality of life measures including: Patient Global Impression of Change (PGIC) and Medical Outcomes Survey Short Form 36 (SF-36), version 2. The SF-36 is comprised of 36 survey questions assessing different domains of function including: physical functioning, role physical, bodily pain, vitality and social functioning.2
Following 12 weeks of treatment:2
- The overall differences in PGIC compared with placebo were significant in the ZORVOLEX 35 mg three times daily (P < 0.0001) and twice daily (P = 0.0008) treatment groups. Two-thirds of patients receiving ZORVOLEX 35 mg three times daily (P < 0.0006) and half of the patients receiving ZORVOLEX 35 mg twice daily (P = 0.0071) reported PGIC as "very much" or "much" improved relative to placebo.
- Patients treated with ZORVOLEX 35 mg three times daily reported statistically significant improvements in 5 SF-36 domains, 4 of which were clinically meaningful (?Minimally Clinical Important Difference). These included physical functioning, role physical, bodily pain and social functioning.
- The most common adverse events (>2%) in studies of ZORVOLEX include: edema, nausea, headache, dizziness, vomiting, constipation, pruritus, flatulence, pain in extremity and dyspepsia.
“Up to 50 percent of all NSAID prescriptions are written for osteoarthritis5, a condition that significantly contributes to disability, especially among older adults,” said Dr. Martin J. Bergman, Clinical Assistant Professor of Medicine at Drexel University College of Medicine, and a study author. “However, NSAIDs, like all pain treatments, have associated risks, particularly at higher doses.6,7 That’s why it’s important to use the lowest effective dose of these agents, particularly in patients with osteoarthritis, who may require long-term treatment.”
ZORVOLEX is the first low dose FDA-approved NSAID developed using proprietary SoluMatrix Fine Particle Technology™ that 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. 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 not approved for the treatment of osteoarthritis pain. A supplemental New Drug Application seeking approval for this indication is currently being reviewed by FDA. For more information, visit www.ZORVOLEX.com.
TIVORBEX is an FDA-approved NSAID developed using proprietary SoluMatrix Fine Particle Technology™. TIVORBEX contains indomethacin 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. TIVORBEX is part of Iroko’s low dose NSAID pipeline, and 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 of time consistent with individual patient treatment goals.
1 Gibofsky, A. Indomethacin Submicron Particle Capsules: Reduced Opioid Rescue Medication Usage in a Phase 3 Study in Patients with Acute Pain After Elective Surgery. Abstract at American Pain Society?s (APS) 33rd Annual Scientific Meeting.
2 Strand V. A Phase 3 Randomized Controlled trial of Lower-Dose Diclofenac Capsules Developed using SoluMatrix Fine Particle Technology in Patients with Osteoarthritis Pain: Impact on Patient-Reported Outcomes. Poster at 2014 Osteoarthritis Research Society International (OARSI) World Congress.
3 TIVORBEX Prescribing Information, pg. 1
4 ZORVOLEX Prescribing Information, pg. 1
5 Atkinson, T. Medication Pain Management in the Elderly: Unique and Underutilized Analgesic Treatment Options. Clinical Therapeutics. 2013.
6 Risser A. (2009 Dec). NSAID Prescribing Precautions. Am Fam Physician. 80(12):1371-1378.
7 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).