Allena Pharmaceuticals announced positive topline results from URIROX-1, a Phase 3 pivotal trial evaluating reloxaliase in patients with enteric hyperoxaluria (EH). The primary endpoint was achieved, showing a statistically significant reduction in urinary oxalate in patients with enteric hyperoxaluria.
URIROX-1 was a multicenter, global, randomized, double-blind, placebo-controlled study conducted to evaluate the safety and efficacy of reloxaliase in 115 patients for a four-week treatment period. Patients were randomized 1:1 to receive either reloxaliase or placebo and took ~240 mg (equivalent to 7,500 units) of reloxaliase or placebo with each meal or snack three to five times per day. The study achieved its primary endpoint, with a mean reduction of 22.6% in average 24-hour UOx excretion measured during Weeks 1-4 among patients treated with reloxaliase, compared to 9.7% in the placebo. Additionally, in a pre-specified secondary endpoint, the stratified analysis of the primary endpoint in bariatric surgery patients (68% of the total study population), patients treated with reloxaliase achieved a mean reduction of 21.2% in average 24-hour UOx excretion, compared to 6.0% for patients treated with placebo.
Results were also reported from Study 206, a multi-center, open-label, single-arm Phase 2 trial designed to enroll between 15 and 20 patients in the United States and Europe aged 12 and older with EH and chronic kidney disease. Patients received ~240 mg (equivalent to 7,500 units) of reloxaliase with each meal or snack five times a day, for 12 consecutive weeks. Data from this trial demonstrated reloxaliase led to substantial reductions in measures of oxalate burden.
A second phase 3 trial, URIROX-2, is currently underway and recruiting patients to determine the efficacy, durability and long-term safety of reloxaliase in patients with enteric hyperoxaluria.
Reloxaliase is an orally administered, recombinant oxalate-degrading enzyme. Reloxaliase targets oxalate in the GI tract in an effort to reduce the burden of both dietary and endogenously produced oxalate. Reloxaliase has the potential to decrease the oxalate available systemically for deposition as calcium oxalate crystals or stones in the kidneys, as well as reduce long-term kidney complications.
Reloxaliase has been granted orphan drug designations by the FDA for the treatment of primary hyperoxaluria and for the treatment of pediatric hyperoxaluria. The European Commission has granted orphan drug designation for reloxaliase for the treatment of primary hyperoxaluria.
Hyperoxaluria is a metabolic disorder characterized by significantly elevated oxalate levels in the urine, due to either overproduction of oxalate by the liver from a genetic defect, called primary hyperoxaluria, or from the excess absorption of oxalate from the diet, called secondary hyperoxaluria. Secondary hyperoxaluria is further characterized either as enteric, resulting from a chronic and unremediable underlying gastrointestinal disorder associated with malabsorption, such as bariatric surgery complications or Crohn’s disease, which predisposes patients to excess oxalate absorption, or idiopathic, meaning the underlying cause is unknown. Kidney stones, typically the first sign of hyperoxaluria, are often painful and may require interventional procedures. Severe hyperoxaluria in settings of enteric and primary hyperoxaluria may also lead to kidney damage (nephrocalcinosis), chronic kidney disease and end-stage renal disease, which may lead to death.