Flexion Therapeutics, Inc. presented data from a Phase II study which found its lead investigational drug candidate, FX006 (Zilretta) was associated with reduced blood glucose elevation compared with immediate release triamcinolone acetonide in crystalline suspension (TAcs) in patients with Type 2 diabetes and knee osteoarthritis (OA).
The full analysis was presented in a poster session on June 11 during the American Diabetes Association’s 77th Scientific Sessions.
Intra-articular injections of corticosteroids are commonly used to manage OA pain and inflammation.
However, the rapid absorption of these immediate-release steroids elevate blood glucose levels.
Among the 4.2 million patients each year who receive knee injections for OA, about 20 percent have diabetes.
“That translates into over 800,000 patients that are subject to this increase in blood sugar,” said Michael Clayman, MD, President and CEO of Flexion in an exclusive interview with Drug Discovery & Development. “Zilretta may significantly reduce those blood glucose spikes by delivering a slower and extended release of corticosteroid in the knee joint and minimizing systemic exposure.”
The double-blind, randomized, parallel-group study examined blood glucose concentrations following a single injection of 40 mg FX006 or 40 mg TAcs. Thirty-three patients with Type 2 diabetes and knee OA who were actively being treated with one or two oral diabetes medications were enrolled in the study and randomized to receive either an immediate release steroid or FX006. Blood glucose levels were monitored continuously for one week prior and for two weeks following treatment.
Results showed patients experienced a significantly lower change in average blood glucose concentration following administration of FX006 (14.7 mg/dL) compared with TAcs (33.9 mg/dL).
FX006 is formulated by taking TAcs and embedding it in a polymer that creates microspheres which slowly dissolve when injected in to the knee joint. “The polymer is really comprised of two sugars,” explains Clayman. “As these microspheres slowly dissolve over three months in the knee joint they release the component parts—the polymers get metabolized and in parallel they release the steroid in therapeutic concentrations that last three months.”
“The pain relief from immediate-release steroids that a patient experiences—which is usually pretty good—typically only last no more than two to four weeks,” added Clayman. FX006 was created to address the issue of the inadequate duration of the adequate pain relief associated with immediate relief steroids. “We formulated Zilretta to achieve therapeutic concentrations or effective concentrations in the joint for three months and we demonstrated that we not only achieved longer relief which was the original goal, but pleasant surprise, we also achieved better relief than seen with the immediate relief steroids—without the spike in blood glucose levels.”
Non-opioid alternative for OA knee pain
Roughly 50 percent of OA patients are prescribed opioids, said Clayman. “When you look at the pain relief that we get with Zilretta and compare it to what’s been published about the pain relief you get with opioids and OA, strictly speaking, ours is better by that comparison. In Zilretta, you have a non-opiod product that’s very well tolerated that achieves pain relief that’s better—based on historical comparisons, we don’t have head-to-head data—than opioids.”
”We all know the opioid epidemic is real, and frankly, based on a recent New York Times article, worsening in terms of overdose deaths,” said Clayman. “Part of our interaction with the U.S. Food & Drug Administration was a request for fast track designation for Zilretta as a non-opioid alternative for the treatment of patients with OA. In fact, the agency did grant us fast track status for this product and we think it’s driven in part by these considerations related to the potential for Zilretta to be a meaningful alternative for patients who might otherwise be prescribed opioids.”
Flexion filed a New Drug Application for FX006 in December 2016. The FDA approved it in February and they have a PDUFA date of October 6, 2017.
“We’ve been preparing for the commercial launch of this product for over two years now. We’ve been building the organization judiciously over time and we are fully committed to the flawless execution around what we think is a compelling plan for launch and commercialization, assuming obviously, approval in the October frame time,” said Clayman. If the time frame is met, Flexion expects to launch the product by the end of 2017.
Filed Under: Drug Discovery