VERU-112 for the Treatment of Gout and Familial Mediterranean Fever

VERU-112

Scientific Overview

Colchicine is a drug that is used for prophylaxis and treatment of gout in adults (0.6-1.2mg/day) and for FMF in adult and children four years and older (0.3-2.4mg/ day depending on age). Gout is a type of arthritis characterized by sudden, severe attacks of burning joint pain, usually the big toe, because of the deposition of uric acid crystals in the joint. The attacks can be recurrent and last a few days to many weeks until there is pain relief. Gout is a disease of high levels of uric acid in the blood and is ten times more common in men than women. Colchicine is effective in preventing and treating acute attacks.

FMF is a hereditary inflammatory disorder caused by mutations in the MEFV gene that causes episodes of fever, pain and swelling in the abdomen (peritonitis), lungs (pleuritis), heart (pericarditis) and joints (arthritis) in adults and children. Signs and symptoms of FMF usually begin in childhood with attacks that last for weeks or months. Colchicine is considered the gold standard and the only drug recommended for treating FMF. Colchicine is used at low doses to prevent and treat these FMF patients chronically.

Colchicine has a narrow therapeutic index which means that the doses required to treat the disease and the occurrences of serious safety issues are close. Colchicine has common side effects such as abdominal cramping, nausea and diarrhea that have limited its use. More concerning, however, colchicine has “warning and precautions” in the label for drug-drug interactions and should not be taken in conjunction with other drugs that are P-gp or strong CYP3A4 inhibitors as this could lead to serious side effects and death. Examples of drugs and other items that could increase the concentration of colchicine in the blood into toxic ranges include certain antibiotics, antidepressants, lipid lowering drugs, tranquilizers, grapefruit juice and antihistamines.

VERU-112 is a new chemical entity, small molecule that has high oral bioavailability, and like colchicine, binds to the “colchicine binding site” of tubulin. Unlike colchicine, there should not be drug-drug interactions, as VERU-112 does not interact with P-gp or CYP3A4. This eliminates the possibility of serious and life-threatening side effects when given with other drugs that are P-gp or CYP3A4 inhibitors. VERU-112 could be used as a potentially safer alternative to colchicine, which remains the mainstay of therapy for both prevention and treatment of gout and FMF.

VERU-112

Market

According to nationally representative data (NHANES), gout is the most common form of inflammatory arthritis in men, with a prevalence of 5.9% in men (6.1 million) and in women the prevalence is 2% (2.2 million). The estimated U.S. annual market for gout therapies is $725 million per IMS. FMF affects primarily people of Mediterranean extraction, mostly Sephardic Jews, Armenians, Arabs and Turks.  It is very common in the populations at risk with estimated carrier rates of 1/6 in Armenians, 1/7 in North African Jews and 1/13 in Iraqi Jews.  FMF affects less than 200,000 patients in the U.S. population and could be eligible for orphan drug status.