Flexion’s Long-Lasting Steroid Injection Hits Mark in Phase 2 Trial

Xconomy Boston — 

[Updated 12 pm with correction] Flexion Therapeutics’ transformation into an osteoarthritis specialist continued gaining traction today, as the Burlington, MA-based company moved its most advanced drug within earshot of a late-stage clinical trial.

Flexion says a drug it calls FX006, a long-lasting form of the steroid triamcinolone, hit its main goals in a 12-week, mid-stage clinical trial involving 228 patients with the degenerative joint disorder.

Flexion only released top-line data—CEO Mike Clayman says the company is “aggressively trying to find the best near-term scientific forum” to present the full details from the study—but it indicated that the drug did a better job of relieving patients’ knee pain, and over a longer period of time, than the immediate-release form of triamcinolone, which is the most commonly prescribed steroid injection. Flexion said the results are statistically significant, meaning that they weren’t due to chance, and that they are good enough to push the drug into a Phase 3 trial.

Mike Clayman, CEO of Flexion Therapeutics

“These are the kind of data that enable a path to IPO, “ Clayman says, “and we know that it’s attracted the interest of potential outside parties.”

In the study, patients with osteoarthritis were either given a low (10 milligram), medium (40 mg), or high (60 mg) dose of FX006, or a 40 mg injection of the immediate-release form of triamcinolone, directly into their knee joint to relieve their pain. Clinicians then measured their pain level by taking down patients’ daily scores on a standardized pain scale—with numbers ranging from 0 to 10—and tabulating a weekly average. Flexion tracked those numbers over the course of 12 weeks.

Flexion didn’t specifically say what the numerical difference was between those taking TCA IR and FX006, or the differences in the results between various dose levels, but Clayman claims the pain relief experienced by patients was “amongst the largest ever seen in clinical trials.” Flexion also said that the pain relief came on as quickly as TCA IR, was well-tolerated, and had a comparable safety profile.

Flexion, of course, will have to reproduce these results in a pivotal trial to get a chance to put its first drug on the market. If it can, it will have the chance to grab a portion of a market that includes about 27 million Americans and 100 million people worldwide, a number that will increase as the population ages. Some 50 million intra-articular injections, or shots given directly into the joint, are given worldwide each year, and about 5 million in the U.S. alone. Those shots bring in about $1.5 billion total annually, according to Flexion.

Patients with osteoarthritis are initially treated with oral drugs before moving on to intra-articular injections of either steroids or hyaluronic acids. They eventually get joint replacements if the pain doesn’t subside. Flexion wants FX006 to replace injectable steroids for patients with knee osteoarthritis, and then hopes to be able to use FX006 to treat osteoarthritis in other joints eventually as well.

Flexion plans to kick off a Phase 3 clinical trial in early 2014, Clayman says.

Flexion was formed in 2007 by Clayman and Neil Bodick, both veterans of Eli Lilly. The concept behind the company was to snap up drugs shelved by Big Pharma and run them through efficient trials to quickly prove if they should be developed or not. After that, Flexion planned to either partner or sell the drugs to an acquirer, use the cash to pick up new drugs, and repeat the process.

[This paragraph has been updated to correct references to investors.]
The mission got plenty of support from Big Pharma names: the venture arm of Pfizer (NYSE: PFE) invested in Flexion, and companies including AstraZeneca and Merck KGaA partnered with the startup to run early-stage clinical trials on drug candidates that had languished inside the larger companies. Flexion raised a total of $75 million in equity financing, with investors including 5AM Ventures and Versant Ventures.

The idea, however, never played out. Flexion found that the licensing deals it was carrying out to get these drugs were becoming less lucrative, including smaller up-front payments and more option-based deal triggers, and didn’t want to bear the majority of the risk for the drugs it picked up.

So instead, Flexion took one drug it had acquired from AstraZeneca—now known as FX005—and used it as the bedrock to turn itself into an osteoarthritis specialist. It began developing the compound, added FX006—which it created in-house and built an IP portfolio around—and filled the portfolio out by in-licensing a second drug from AstraZeneca, known as FX007.

Flexion’s new idea is to capitalize on a market with inefficient treatments and use its three drugs to cover the different stages of osteoarthritis progression. Clayman says that oral drugs either have limited efficacy or safety issues and common steroid injections just don’t last that long.

Its strategy, for example, is to place FX006 after oral treatments; position FX005, which inhibits a protein known as p38 MAP kinase that is implicated in inflammation, for people in which steroid injections don’t work; and then place FX007, which curbs pain by blocking a different kinase, as a last option before something like a knee replacement.

“We’re not a rifle shot,” Clayman says, referring to the idea of being a one-drug company. “We’re building a franchise that has an opportunity to make a real and lasting difference in this space for patients who have limited treatment options.”

Whether it works out remains to be seen. Flexion has to run a pivotal trial for FX006, hasn’t completed mid-stage clinical trials for FX005 yet, and hasn’t even started clinical trials for FX007. But the success of this trial is a good start.

“We’ve been at this now for over five and a half years,” he says. “We’re finally seeing the fruits of our labors, and we’re fortunate enough to have clinical data that is as encouraging as it is.”