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Flexion Therapeutics Reports Primary Endpoint Met in Clinical Trial

By Flexion Therapeutics Inc. | November 2, 2016

Study evaluated investigational drug candidate Zilretta in Type 2 diabetes patients with knee osteoarthritis.

Flexion Therapeutics Inc. is reporting top-line results from a clinical trial to assess the effects of its investigational lead drug candidate, Zilretta (also known as FX006), on blood glucose levels in adults with osteoarthritis (OA) of the knee who also have Type 2 diabetes.  Results from the trial demonstrated Zilretta is associated with a statistically significant (p<0.05, two-sided) and clinically relevant reduction in the rise of blood glucose compared to that observed following immediate-release (IR) triamcinolone acetonide (TCA) injection in patients who also have knee OA. Zilretta has previously demonstrated clinically meaningful improvement of pain, stiffness and function in its Phase 3 pivotal trial in patients with knee OA.
The objective of the double-blind, randomized, parallel group, single-dose study was to examine if Zilretta had effects on blood glucose levels that differ from IR TCA. Investigators from seven study sites enrolled 33 patients, randomized one to one to receive a single intra-articular injection of 40 mg Zilretta or 40 mg IR TCA. Blood glucose levels were evaluated for a total of three weeks (one week prior to injection and two weeks post injection) using a continuous glucose monitoring device. Patients returned for follow up visits at day eight, day 15 and week six/day 43. The primary endpoint compared the change in average glucose values from the period of 72 hours before to the period 72 hours after injection with Zilretta versus IR TCA. 
"It is well-known that immediate-release corticosteroids can cause substantial elevations in blood glucose among patients with diabetes following an intra-articular injection, an effect that is likely tied to peak plasma concentrations. Because pharmacokinetic studies have shown that Zilretta is associated with much lower peak plasma concentrations, we hypothesized that any rise in glucose after a Zilretta injection would be negligible. The data are consistent with this hypothesis and we are enthusiastically looking forward to presenting the detailed study results at an upcoming scientific forum," said Michael Clayman, M.D., Flexion Therapeutics' president and CEO. "We believe these data demonstrate that Zilretta may limit effects on blood glucose which, if approved, could have future implications for the many knee OA patients in the U.S. who also have Type 2 diabetes. We look forward to including these topline data in the Zilretta new drug application (NDA) which we plan to submit by the end of the year."
"Disruption of glucose control following intra-articular glucocorticoid injections is a problem for patients with diabetes mellitus," said Steven J. Russell, M.D., Ph.D., assistant professor of medicine, Diabetes Research Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School. "Initial analysis of the data from this carefully designed study suggests that Zilretta may not disrupt glucose control in people with type 2 diabetes who need intra-articular steroid injections for knee osteoarthritis. Enabling steroid treatment without glucose disruption would be an important clinical advance for patients with diabetes who are candidates for glucocorticoid injections."

While OA is currently being diagnosed at increasingly younger ages, prevalence rises after age 45. In 2015, more than 14 million Americans were diagnosed with OA of the knee. OA represents an enormous burden on the U.S. healthcare system, affecting more than 27 million individuals and accounting for more than $185 billion in annual expenditures. These costs are expected to rise with a predicted increase in OA prevalence, which is expected to affect 67 million Americans by 2030.
Each year, more than 5 million OA patients in the United States receive immediate-release corticosteroid and hyaluronic acid intra-articular injections for knee pain, but these injections generally provide limited relief, and no alternative injectable therapy has been approved in more than a decade.
Zilretta is being investigated as the first intra-articular extended-release, non-opioid treatment for patients with moderate to severe knee OA pain. Zilretta employs proprietary microsphere technology combining TCA—a commonly administered, short-acting corticosteroid—with a polymer (PLGA) intended to provide persistent concentrations of drug locally to both amplify the magnitude and prolong the duration of pain relief.
To date, more than 600 patients have been treated with Zilretta in clinical trials. No drug-related serious adverse events have been observed in these trials and adverse events have typically been localized, mild and comparable to those observed with immediate-release TCA and placebo. The data from these trials are consistent with Zilretta providing meaningful and durable pain relief.
Flexion is a specialty pharmaceutical company focused on the development and commercialization of novel, local therapies for the treatment of patients with musculoskeletal conditions, beginning with OA. The company's lead product candidate, Zilretta, is being investigated for its potential to provide improved analgesic therapy for the millions of U.S. patients who receive intra-articular injections for knee OA annually. The company is based in Burlington, Mass.
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