Benzinga | Jan 4, 2021 07:34AM EST

Dicerna Announces Enrollment Completion Of PHYOX2 Pivotal Trial Of Nedosiran For Treatment Of Primary Hyperoxaluria

-- Dicerna Expects Trial Completion in First Half of 2021, With Top-Line Data Available Mid-Year --

-- Enrollment in PHYOX4 Trial for PH3 Expected to Begin in January 2021 --

-- Planned New Drug Application Submission On Track for Third Quarter of 2021 --

Dicerna Pharmaceuticals, Inc. (NASDAQ:DRNA) (the "Company" or "Dicerna"), a leading developer of investigational ribonucleic acid interference (RNAi) therapeutics, today announced enrollment completion in the Company's PHYOX(tm)2 pivotal, double-blind, randomized, placebo-controlled clinical trial of its lead investigational therapy, nedosiran, which is in development as a once-monthly treatment of all three known types of primary hyperoxaluria (PH) -- PH1, PH2 and PH3. PH is a family of ultra-rare, life-threatening genetic disorders that initially manifest with complications in the kidneys. The Company expects the last patient visit in the PHYOX2 trial to occur in the first half of 2021 and to report top-line results from the study mid-year.

"This milestone reflects the significant progress we've made in the PHYOX clinical trial program this year in spite of the challenges presented by the COVID-19 pandemic. We are grateful to all of our collaborating investigators and participants for their commitment. With enrollment in our pivotal study of nedosiran for PH now completed, we are one step closer to potentially providing a convenient and differentiated treatment option that addresses the underlying cause of disease for patients with PH1, PH2 and PH3," said Shreeram Aradhye, M.D., Executive Vice President and Chief Medical Officer at Dicerna. "We look forward to sharing top-line results from PHYOX2 later this year, with the goal of submitting a New Drug Application for nedosiran in the third quarter of 2021."

The PHYOX2 multicenter pivotal trial (NCT03847909) is designed to evaluate the efficacy and safety of nedosiran delivered as a once-monthly subcutaneous injection in participants aged six years and older who have PH1 or PH2. The primary endpoint of the study is the percent change from baseline in 24-hour urinary oxalate excretion between Days 90 and 180. Enrollment of 35 participants was completed in December 2020 and included participants across 11 countries, including the U.S., Japan and Europe.

PHYOX2 is part of the broader PHYOX clinical trial program designed to evaluate nedosiran in PH1, PH2 and PH3 patients of all ages and stages of chronic kidney disease. The PHYOX4 trial in patients with PH3 is now expected to begin enrollment in January 2021. Data from PHYOX1, PHYOX2, PHYOX4, the ongoing PHYOX3 open-label extension study, and the PHYOX-OBX natural history study of PH3 participants, are expected to form the basis of the nedosiran New Drug Application (NDA) submission. The Company anticipates initiating supplemental studies, including PHYOX7 in patients with end-stage renal disease, and PHYOX8 in pediatric patients younger than six years of age, in the first and second quarters of 2021, respectively.

Participants who complete PHYOX trials are eligible to enroll in the Company's PHYOX3 trial, an ongoing open-label extension study evaluating nedosiran's long-term safety and efficacy. An interim analysis of the PHYOX3 trial presented at the American Society of Nephrology's Kidney Week 2020 annual scientific conference in October 2020 showed all participants receiving nedosiran, regardless of PH1 or PH2 subtype, achieved normalization or near-normalization of urinary oxalate (Uox), a key PH measure, by Day 180. Of the 13 participants who reached Day 180 as of the interim analysis, 10 (100%) of the participants with PH1, and two of the three (67%) participants with PH2, achieved normal Uox excretions at one or more visits, and 62% of all participants achieved normal Uox excretions on at least three consecutive visits, meeting protocol-defined eligibility for gradual reduction in fluid intake requirements.