US-based biopharmaceutical firm CymaBay Therapeutics has dosed the first patient in a Phase IIb clinical trial of arhalofenate (MBX-102), a dual acting product candidate for the treatment of gout that is targeted to lower serum uric acid (sUA) and reduce the incidence of flares.
The study will assess the safety, flare prevention and sUA-lowering activity of arhalofenate in 225 patients with a diagnosis of gout, hyperuricemia and a history of three or more flares in the past one year.
The randomised, double-blind, active comparator and placebo-controlled trial has five arms including placebo, arhalofenate (600mg and 800mg), allopurinol (300mg) and allopurinol (300mg) plus colchicine (0.6mg).
The trial’s primary endpoint is the flare incidence rate for the arhalofenate (800mg) arm versus allopurinol (300mg) following 12 weeks of treatment, while the secondary endpoint is the sUA responder rate (the percentage of patients that achieve sUA levels below 6 mg/dL) for the treatment arms.
The trial is designed to evaluate whether arhalofenate can provide sUA lowering comparable to the most commonly prescribed dose of allopurinol (300mg) and flare reduction similar to colchicine, the drug most commonly used to prevent sUA-lowering induced flares.
CymaBay president and CEO Harold Van Wart said: "Arhalofenate’s dual mechanism is ideal for patients not reaching treatment goals.
"We are pleased to announce that we have met this important milestone which we projected for the first half of this year."
Previously, arhalofenate was under development for the treatment of type 2 diabetes and the glucose lowering exhibited by the drug did not meet the desired product profile for this indication.
Arhalofenate was studied in eight Phase I and four Phase II trials in which it showed good safety and tolerability in over 550 patients for up to six months of treatment.
However, data from these trials demonstrated that the drug exhibited dose-dependent reductions in sUA, which is due to a uricosuric effect where the drug blocks the reabsorption of uric acid from the kidneys mediated by the transporter URAT-1, resulting in increased renal clearance into urine.