Allena Pharmaceuticals announced positive topline results from the phase 3 URIROX-1 trial of reloxaliase for the treatment of enteric hyperoxaluria (EH), as well as additional data from the phase 2 trial (Study 206) in high-risk patients with EH and advanced chronic kidney disease (CKD).
Reloxaliase is a first-in-class, crystalline formulation of the enzyme oxalate decarboxylase that is designed to limit the systemic absorption of oxalate by breaking oxalate down within the gastrointestinal tract. Decreased systemic absorption reduces the burden on the kidney to filter and excrete oxalate.
URIROX-1 is a multicenter, global, randomized, double-blind, placebo-controlled study that evaluated the safety and efficacy of reloxaliase in 115 patients for 4 weeks. Patients were randomized 1:1 to receive either reloxaliase ~240mg (equivalent to 7500 units) or placebo with each meal or snack 3 to 4 times daily.
Results showed that reloxaliase treatment was associated with a statistically significant mean reduction of 22.6% from baseline in average 24hr urinary oxalate (UOx) excretion during Weeks 1-4 (primary end point) compared with 9.7% with placebo (LS mean treatment difference of -14.3%; P =.004). Similarly, a stratified analysis of the primary end point in bariatric surgery patients showed a mean reduction of 21.2% in average 24hr UOx excretion with reloxaliase compared with 6.0% in the placebo group (LS mean difference of -16.2%; P =.01).
Additionally, 48.3% of reloxaliase-treated patients achieved a ≥20% reduction from baseline in 24hr UOx excretion (secondary end point) compared with 31.6% in the placebo group (P =.06). A stratified analysis in bariatric surgery patients showed 50.0% of reloxaliase-treated patients achieved the secondary end point vs 28.9% in the placebo group (P =.036).
In Study 206, an open-label, single-arm phase 2 trial, the safety and efficacy of reloxaliase was evaluated in patients aged ≥12 years with EH and advanced CKD (N=20) for 12 weeks. Patients received reloxaliase ~240mg (equivalent to 7500 units) with each meal or snack 3 to 4 times daily. Substantial reductions were observed in the 24hr UOx excretion as well as plasma oxalate (POx) levels over Weeks 4 to 12.
Regarding safety, reloxaliase was generally well-tolerated in both studies with no adverse events leading to treatment discontinuation.
Data from URIROX-1 and Study 206 will be presented in poster presentations at the American Society of Nephrology (ASN) Annual Meeting 2019 in Washington, DC.
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