Are Regeneron's Gout Drug Trial Results Really Bad News?

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Regeneron’s (NASDAQ:REGN) Phase 3 study in gout patients initiating allopurinol therapy to lower their uric acid levels showed that the company’s drug Arcalyst (rilonacept), known as IL-1 Trap, prevented gout attacks, as measured by the primary endpoint of the number of gout flares per patient over the 16 week treatment period.

Is this good or bad news?

Judging from investors’ reaction to the news, one would believe the clinical trial results are a failure. However, judging based on understanding the disease, its causes, complications, symptoms and what current conventional treatments are accomplishing (or lacking), would prove that Arcalyst might be the missing link in the treatment of gout. The drug neutralizes a major mediator of the severe attacks of inflammatory-symptom flare up the patients suffer from after taking the uric acid lowering drugs, which is the fundamental treatment of gout. That’s what makes the bulk of patients abandon the treatments that deal with the cause of disease, i.e., elevated uric acid. No conventional drug taken at a safe dose has been effective in preventing the flare up of the symptoms, which take their toll on patients and probably lead to worsening of the disease. It is easier for gossipers to perpetrate skepticism towards Regeneron’s drug Arcalyst if the listeners do not understand what gout is and what treatments are required for its successful management. The fact is that gout requires more than two classes of drugs to stop the main cause of this disease, control its disabling symptoms, and prevent the attacks, thus, the consequent complications of the disease are not well treated.

Gout occurs in patients who have elevated levels of uric acid. The uric acid is deposited in the joints and other body tissues. In the joints uric acid causes joint inflammation, joint pain, stiffness swelling, redness and heat. Deposited in soft tissues, uric acid causes the same effect as it does in the joints. Generally, patients experience flare up of symptoms that no drug is yet capable of preventing. The current management of gout aims first at lowering uric acid by either decreasing its formation or increasing its elimination from the body with uric acid-lowering drugs. Drugs exist that can tackle one or the other of the two actions. For example, the drug Allopurinol decreases uric acid formation and Probenecid helps the body eliminate excess uric acid through the kidneys and into the urine. The problem is that controlling the level of uric acid does not stop all the symptoms right away but the pain and suffering might increase and persist for long. The reason is that the breakup of uric acid crystals boosts inflammatory mediators, especially interleukin-1 (IL-1), which causes the flare. IL-1 is targeted for inhibition by Regeneron’s drug Arcalyst. The flare the patients experience after the treatment makes it difficult for them to adhere to uric acid-lowering therapies and they discontinue the treatment within the first few months of therapy. That’s why Arcalyst is badly needed.

Currently, physicians are using the anti-inflammatory drug colchicine to calm down inflammation. In many cases, however, the dose required for the control of severe inflammatory symptoms is high and must be taken for a long time, which makes its side effects prohibiting. Patients would suffer severe diarrhea, abdominal cramps, nausea, and vomiting. Non-steroid anti-inflammatory drugs are used also, but in many cases they do not control the severe inflammatory symptoms during the flare, unless very high doses are given for a long time. Long-term use of high dose can provoke grave side effects, including peptic ulcer, kidney failure and liver failure. Steroids are resorted to, yet, again, their long-term high dose use could result in detrimental side effects, which go from immune system suppression, to osteoporosis, bone fracture, endocrine system deregulation, difficulty of wound healing, diabetes and the list goes on and on.

So, the most important result from Arcalyst phase 3 study is the one which confirms that the concomitant use of the drug with uric acid-lowering therapy for the first several months may help avoid gout flares. The use of Arcalyst is expected to improve patients’ adherence to uric acid lowering drugs, sustain their well-being and improve the outcome of their disease. Is this bad news?