Dicerna Pharmaceuticals, Inc. announced results of the PHYOX?2 pivotal clinical trial of nedosiran, an investigational GalXC? RNAi candidate for the treatment of primary hyperoxaluria (PH), in a late-breaker poster presentation at the American Society of Nephrology (ASN) Kidney Week 2021. In the PHYOX2 pivotal trial, which included patients with PH type 1 (PH1) and PH type 2 (PH2), nedosiran demonstrated a statistically significant reduction from baseline in urinary oxalate (Uox) excretion compared to placebo (p<0.0001). Additionally, a significantly higher proportion of patients treated with nedosiran achieved and sustained normal or near-normal Uox at two or more consecutive visits after Day 90 compared to placebo (p=0.0025). A post hoc subgroup analysis in participants with high baseline Uox (at least one value = 1.6 mmol) also showed significantly greater Uox reduction in those treated with nedosiran (p=0.0186). These robust and sustained Uox reduction results observed in PHYOX2 were primarily driven by response to nedosiran in the PH1 subgroup, which met both primary and key secondary endpoints based on a post hoc analysis. There was no consistent pattern of Uox reduction observed in participants with PH2. Separately, findings from a real-world study examining de-identified electronic medical record (EMR) data, including demographics, clinical characteristics and healthcare utilization among 47 patients with PH pre- and post-dialysis treatment were also presented at the conference. The study showed high rates of costly healthcare utilization, including emergency and inpatient visits, and confirmed that healthcare costs continued to be substantial, exceeding $200,000, in the first year following dialysis initiation. More than half of patients had no recorded PH diagnosis until after initiating dialysis. PHYOX2 (NCT03847909), a placebo-controlled, double-blind, multicenter, pivotal study, was designed to evaluate the efficacy, safety and tolerability of nedosiran over six months in participants with PH1 or PH2 aged six years and older across 11 countries, including the U.S., Japan and Europe. Participants were randomized 2:1 to a fixed dose of nedosiran or placebo administered once monthly by subcutaneous injection. The primary endpoint of the study was the percent change from baseline in 24-hour Uox excretion, as assessed by area under the curve (AUC) from Day 90 to Day 180. The key secondary endpoint was percentage of patients (PH1 and PH2) achieving normalization (defined as Uox level below 0.46 mmol adjusted per 1.73 m2 body surface area in participants younger than 18 years when collected over 24 hours) or near-normalization (defined as 1.3 times the upper limit of normal; 0.60 mmol) on at least two consecutive visits from Day 90 to Day 180. Of the 35 patients randomized (23 nedosiran and 12 placebo; 29 with PH1 and 6 with PH2), 34 participants had at least one efficacy assessment after Day 90 (modified intent-to-treat population; mITT). Baseline mean estimated glomerular filtration rate (eGFR; a measure of kidney function) was 89.5 mL/min/1.73 m2 (SD=37.5) for participants given nedosiran and 82.0 mL/min/1.73 m2 (SD=30.0) for participants given placebo. Baseline mean Uox values were 1.33 mmol/day (SD=0.47) and 1.96 mmol/day (SD=0.71) for the nedosiran and placebo groups, respectively. Nedosiran achieved the primary endpoint showing a statistically significant reduction from baseline in Uox excretion compared to placebo (p<0.0001). PHYOX2 also achieved its key secondary endpoint, with a significantly higher proportion of patients treated with nedosiran achieving and sustaining normal or near-normal Uox at two or more consecutive visits after Day 90 compared to placebo (50% vs. 0%; p=0.0025). Of the participants treated with nedosiran, 73% achieved normalization or near-normalization at least once during the study.