Extended-Release Corticosteroid Study for Shoulder OA Begins

Burlington, Massachusetts-based Flexion Therapeutics, Inc. has begun a study of an extended release corticosteroid for shoulder osteoarthritis (OA) and adhesive capsulitis (AC) trial. In addition, the company announced progress on gene therapy for knee osteoarthritis.

The blinded, proof of concept study will evaluate the efficacy and safety of Zilretta—triamcinolone acetonide extended-release injectable suspension—in patients with either shoulder osteoarthritis or AC, also known as frozen shoulder. The placebo-controlled study is expected to enroll up to 250 patients—approximately 135 with shoulder osteoarthritis and 115 with shoulder adhesive capsulitis.

Michael Clayman, M.D., Flexion president and CEO, told OTW, “We have been greatly encouraged by the success of Zilretta for knee osteoarthritis and are seeing substantial excitement among orthopedic surgeons who see the potential for treating shoulder conditions such as adhesive capsulitis and osteoarthritis. We decided to move rapidly into those indications with the goal of expanding the label. Our vision for Zilretta is that it will be a frontline treatment for knee osteoarthritis and a frontline treatment for shoulder osteoarthritis and adhesive capsulitis.”

In addition, states Dr. Clayman, Flexion is entering the gene therapy arena. “We have a potentially game-changing gene therapy product, FX201, which is in clinical trials and is injected directly into the knee joint to treat osteoarthritis. FX201 is a viral vector which is injected directly into the knee joint and results in the expression of a powerful anti-inflammatory protein, interleukin-1 receptor antagonist (IL-1Ra).”

“This construct was developed by gene therapy leader Brendan Lee, M.D., Ph.D. from Baylor University and we in-licensed it through GeneQuine Biotherapeutics GmbH. One of the elegant elements of this genetic construct is that there is a ‘promoter’ upstream from the gene…a switch that is on/off. When it is ‘on,’ the gene produces the protein; when it is ‘off’ the gene is silenced. What flips the switch is the presence of inflammation. When the inflammatory promoter turns on it cranks out IL-1Ra which tamps down the inflammation and shuts down the gene.”

“We have animal data showing that a single injection can provide at least one year of symptomatic relief; other preclinical data, including that in a large animal model indicate that treatment can slow the progression of osteoarthritis.”

“So taken together with Zilretta truly beginning to hit its stride, including very positive spontaneous feedback from many patients who have received knee injections, the ongoing Zilretta shoulder trial and the fact that FX201 is now in the clinic, there has never been a more exciting time at Flexion.”