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Nedosiran explored in primary hyperoxaluria type 3


The RNAi drug nedosiran is a once-monthly subcutaneous injection under investigation for all 3 types of primary hyperoxaluria.

Patient dosing has started in the PHYOX4 trial, which is evaluating nedosiran in patients with primary hyperoxaluria type 3 (PH3), according to Dicerna Pharmaceuticals, the company developing the RNAi drug.1

Nedosiran is a once-monthly subcutaneous injection under investigation for all 3 types of PH, a rare, inherited condition characterized by recurrent kidney and bladder stones. Each PH type results from a mutation in a different gene. Dicerna noted in a press release that there are about 4100 patients in the United States with PH3; accordingly, the study’s target enrollment is only 6 patients.

In the PHYOX4 study (NCT04555486), patients aged ≥6 years with PH3 will receive a single dose of nedosiran. The primary end point is safety, with secondary end points including plasma pharmacokinetics and response, defined as having a ≥30% decrease from baseline in 24-hour urinary oxalate (Uox) on 2 consecutive visits. Initial study results are anticipated in mid-2021.

“PH3 is the most recently characterized genetic subtype of primary hyperoxaluria and represents an area of significant unmet need,” Shreeram Aradhye, MD, executive vice president and chief medical officer at Dicerna, stated in the press release. “With dosing in our PHYOX4 PH3 trial underway, we have achieved another important milestone on our path to develop nedosiran as a potential treatment for all 3 genetically defined PH subtypes.”

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).

The company recently announced that enrollment has been completed in the pivotal PHYOX2 trial exploring nedosiran in patients with PH1 and PH2.2

Those patients enrolled in any PHYOX trial, including PHYOX4, 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 180.2

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 Initiates PHYOX™4 Trial of Nedosiran for Primary Hyperoxaluria Type 3. Published on February 11, 2021. Accessed February 26, 2021. https://bit.ly/3bKfi6S.

2. 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.

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