FDA new drug application filing expected by the end of 2021.
Enrollment has been completed in the pivotal PHYOX2 trial exploring nedosiran in patients with primary hyperoxaluria (PH) types 1 and 2 (PH1 and PH2), according to Dicerna, the company developing the RNAi drug.1
Nedosiran is a once-monthly subcutaneous injection under investigation for all 3 types of PH. Dicerna anticipates having top-line data to report in mid-2021, and plans to submit a new drug application to the FDA by the end of the 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,” Shreeram Aradhye, MD, executive vice president and chief medical officer at Dicerna, stated in a press release.
“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,” added Aradhye.
The double-blind, placebo-controlled, randomized PHYOX2 trial (NCT03847909) is assessing the safety and efficacy of nedosiran in patients with PH1 or PH2 who are aged ≥6 years. The target enrollment has been reached with 35 patients, who have been accrued across 11 countries, including Japan, Europe, and the United States. The primary end point of the trial is the percent change from baseline in 24-hour urinary oxalate (Uox) excretion between says 90 and 180. The estimated primary completion goal is June 2021.
Dicerna’s PHYOX clinical trial program consists of multiple nedosiran clinical studies, including PHYOX1, PHYOX2, PHYOX4, the PHYOX-OBX natural history study of patients with PH3, and the ongoing open-label PHYOX3 extension trial. Upcoming studies will also explore nedosiran in end-stage renal disease (PHYOX7) and in patients aged ≤6 years (PHYOX8).
Those patients enrolled in other PHYOX trials who complete their treatment are eligible to enroll in the PHYOX3 extension trial. Results from an interim analysis of PHYOX3 were shared during the American Society of Nephrology’s Kidney Week 2020 annual scientific conference. The findings showed that regardless of PH subtype, all patients receiving nedosiran reached either normalization or near-normalization of Uox by day 180.
Normal Uox excretions at 1 or most visits were achieved by all 10 PH1 patients who reached day 180 of the interim analysis, and by 2 of the 3 PH2 patients who reached day 180. Further, nearly two-thirds (62%) of all patients achieved normal Uox excretions on 3 or more consecutive visits.
Overall, the treatment paradigm for hyperoxaluria is rapidly evolving. In November 2020, the FDA approved lumasiran (Oxlumo) as the first drug for the treatment of patients with PH1. The drug is approved for both adult and pediatric patients.
1. Dicerna Announces Enrollment Completion of PHYOX™2 Pivotal Trial of Nedosiran for Treatment of Primary Hyperoxaluria. Posted online January 4, 2021. Accessed February 9, 2021. https://bwnews.pr/3q7FvSP.