Flexion Therapeutics reports primary endpoint met in pivotal Phase 3 trial of Zilretta in knee osteoarthritis

Flexion Therapeutics, Inc. has reported that the Phase 3 clinical trial for its lead drug candidate Zilretta (also known as FX006) met its primary endpoint at week 12, demonstrating highly significant (p<0.0001), durable and clinically meaningful pain relief against placebo in patients with moderate to severe osteoarthritis (OA) knee pain. In addition, Zilretta achieved statistically significant analgesia against placebo at weeks 1 through 16 and patients treated with Zilretta experienced, on average, a 50 percent reduction in pain from baseline over weeks 1 through 12. In pre-specified analyses, Zilretta achieved statistical significance against placebo in validated OA and quality of life secondary measures through week 12.

In pre-specified secondary measures, compared to immediate-release triamcinolone acetonide (TCA), the most commonly injected intra-articular (IA) corticosteroid, Zilretta achieved statistical significance through 12 weeks on WOMAC A1 (pain), WOMAC B (stiffness) and WOMAC C (function) and the validated Knee injury and Osteoarthritis Outcome Score (KOOS) quality of life subscale and was numerically superior at weeks 2 through 12 on the daily pain rating scale, although it did not achieve statistical significance in that measure.

The frequency of treatment-related side effects was comparable across all treatment arms in the trial. No drug-related serious adverse events were observed and no patients treated with Zilretta were discontinued from the study due to a treatment-related side effect.

"We are extremely gratified with these Phase 3 data that strongly reinforce Zilretta's previous clinical efficacy results, which are consistent with substantial and durable pain relief," said Flexion Therapeutics President and Chief Executive Officer Michael Clayman, M.D. "We believe that Zilretta has the potential to become an important new non-opioid treatment in a therapeutic area that hasn't seen meaningful innovation in many years. More than 12 million people in the U.S. suffer from the painful and debilitating effects of knee OA and many have not found effective relief with existing therapies. We look forward to working closely with the U.S. Food and Drug Administration (FDA) as we prepare to submit our New Drug Application (NDA) for Zilretta."

Zilretta was designed using proprietary microsphere technology and is intended to provide localized and long-lasting pain relief over a period of months while minimizing systemic exposure and avoiding serious side effects common to oral therapies prescribed for OA pain. Current oral treatment options for OA knee pain include non-steroidal anti-inflammatory drugs (NSAIDS), COX II inhibitors and opioids. All are labeled with black box warnings for serious, sometimes fatal, side effects. IA medicines, such as immediate-release corticosteroids and hyaluronic acid injected into the joint, are generally well-tolerated but fail to produce pain relief of sufficient magnitude or duration.

"There have been no major advances in the treatment of OA for decades and given the limited efficacy and the safety liabilities of available therapies, patients are in need of a new treatment option," said Stan Cohen, M.D., Medical Director, Metroplex Clinical Research Center and Clinical Professor of Internal Medicine, UT Southwestern Medical School, Dallas. "These data suggest that Zilretta has the potential to be a significant advance in pain management for patients with OA of the knee."

About the Phase 3 Trial

The randomized, double-blind Phase 3 placebo-controlled, active-comparator trial enrolled 486 patients at approximately 40 centers worldwide. Patients were randomized to one of three treatment groups (1:1:1) and received either a single IA injection of 40 mg of Zilretta, normal saline (placebo) or 40 mg of immediate-release TCA. Each patient was evaluated for efficacy and safety during seven outpatient visits over 24 weeks after receiving an injection. The primary objective of the study was to assess the magnitude of pain relief of Zilretta at 12 weeks against placebo. The secondary objectives of the study were to assess the magnitude and duration of pain relief and effect of Zilretta against placebo and immediate-release TCA in a variety of additional pre-specified measures.

Flexion plans to present detailed results from the Phase 3 clinical trial at an upcoming scientific meeting.