Regeneron’s (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 s 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 who abandon the treatments that deal with the
cause of disease, i.e., elevated uric acid. of the cause of disease. 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 if the disease is 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 it does
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 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 results 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 wellbeing
and improve the outcome of their disease. Is this bad news?
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