About Gout
Gout is a health problem that causes inflamed, painful joints and many other related conditions in millions of people globally. The symptoms are caused by deposits of urate crystals in and around joints and other tissues. The disease is more prevalent in men than women and is often linked with obesity, high blood pressure, high levels of lipids in the blood (hyperlipidemia), and diabetes. Often associated with inflammatory arthritis, it may lead to sudden attacks of joint pain, swelling and redness around affected joints and in some cases can lead to lumpy deposits seen under the skin called tophi. It can also lead to the development of kidney stones.
How Hyperuricemia Contributes to Gout
Gout is caused by elevated levels of serum uric acid, which, if found in high enough concentrations, may form crystals that ultimately get deposited in a patient’s tissues. Uric acid is produced as a result of the breakdown of purines by the enzyme xanthine oxidase. The presence of too many purines, often due to the overconsumption of purine rich foods, can lead to elevated levels of uric acid. Additionally, a patient’s kidneys may have difficulty eliminating uric acid, or other metabolic issues may exist that lead to elevated levels of uric acid.
Foods high in purines include alcoholic drinks and sugary drinks high in fructose; certain meats, such as game meats, kidney, brains, and liver; dried beans and dried peas; and seafood, such as anchovies, herring, scallops, sardines, and mackerel.
Providing Gout Patients with New Opportunities
The current standard of care for most patients with gout is treatment with pain killers and a drug, allopurinol, that inhibits the enzyme xanthine oxidase (XO). Inhibiting XO reduces the production of uric acid. Allopurinol is an effective drug in a majority of patients. It works by being metabolized into an active subunit, oxypurinol which performs the XO inhibition. Unfortunately, roughly 3-5% of patients do not tolerate allopurinol therapy exhibiting multiple side effects. It is hypothesized that when allopurinol is metabolized, toxic free oxygen radicals are released that cause damage. Additionally, some allopurinol becomes allopurinol-nucleotide molecules which may also be problematic. For those patients, the drug febuxostat was developed and commercialized. The drug was effective reaching peak sales in the US of roughly $450M US, but unfortunately it had unacceptable side effects including causing sudden cardiac death in some patients and received a Black Box warning by the FDA. XORTX has developed a proprietary formulation of oxypurinol, the active subunit of allopurinol which is safer than and as effective as allopurinol. This drug has been used in over 750 allopurinol intolerant patients with very positive results. XORTX plans to bring this drug to market in 2026.