Whither Flexion?

As a part-time practicing physician (rheumatology), it has been gratifying to see the advent of effective new therapies for the treatment of many rheumatological disorders such as rheumatoid arthritis, psoriatic arthritis, etc. What is amusing, if that be the correct word, is that the treatment of the most common rheumatologic disease, osteoarthritis, has been relegated to the backwaters of antiquated practice. Not much has changed over the past 30 years. The mainstay of treatment remains pain management with non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, and various equally ineffective intra-articular therapies such as a myriad of hyaluronic acids.

Intra-articular steroids (NOT oral or intravenous) are also commonly used. While steroids offer short term pain control, their long-term safety was always suspect. It has now come into sharp focus, with the publication of a paper in Radiology, the official journal of the Radiology Society of North America. The paper by Kompel et al. demonstrates that injecting all comers of hip and knee OA could actually cause more harm than good, and that patient selection should be methodical, based on individual patient characteristics. This is in marked contrast to the prevalent attitude of rheumatologists and orthopedic surgeons, who never see a joint they don’t like to inject. If patient selection was done carefully, only a fraction of joints would be injected, but with better outcomes.

From an investment point of view, most steroids such as solumedrol are dirt cheap and the companies that make them don’t make much money. The exception is Flexion (FLXN), whose raison d'etre is its intra-articular steroid therapy, Zilretta. In theory, the product is less systemically absorbed and has longer half-life in the joint. So from a safety point of view, it stays in the joint longer, and can have even more devastating effects if administered to a patient who is not a good candidate. If rheumatologists and orthopedic surgeons were to read the paper by Kompel et al and follow its advice, perhaps only a fraction of patients who are estimated by the esteemed analysts to be candidates for Zilretta would actually get it. This would dent the sales of Zilretta, and affect stock price of Flexion considerably.

On another note, the FDA extended the PDUFA date for approval for the repeat dose of Zilrettta. Do they also have qualms about the safety of repeat dose administration of a steroid into the knee? Stay tuned.