Dicerna reports positive interim data from PHYOX-3 extension study of Nedosiran in PH

The PHYOX-3 trial is an ongoing, open-label extension study evaluating nedosiran’s long-term safety and efficacy in participants with primary hyperoxaluria (PH), a family of ultra-rare, life-threatening genetic disorders that initially manifest with recurrent renal stones and can lead to kidney failure. The PHYOX3 trial is open to participants six years of age or older with PH1 or PH2 who have participated in any previous PHYOX clinical development program trial, as well as their siblings with PH between the ages of six to 18. The study’s primary endpoint will evaluate annual rate of decline in estimated glomerular filtration rate (eGFR), a measure of kidney function and nedosiran’s ability to preserve remaining kidney function. The PHYOX3 trial also will evaluate nedosiran’s long-term safety and effect on new stone formation, nephrocalcinosis, and the durability of reducing Uox levels, as well as its potential to enable the gradual decrease or elimination of their disease management practices. 

A total of 16 trial participants from the completed PHYOX1 trial entered the PHYOX3 trial. Of these, 13 who had reached 180 Days and had received six monthly doses in the PHYOX3 trial were included in this analysis. Three participants were not included in the efficacy analysis as they had not yet reached Day 180 at the time of the analysis. 

  • All participants in this analysis, regardless of PH subtype, achieved normal or near-normal Uox excretion by Day 180.
  • 92% of all participants (12 of 13) achieved normal Uox excretion at one or more visits through Day 180:
    • 100% of participants (10 of 10) with PH1
    • 67% of participants (2 of 3) with PH2
  • The single participant with PH2 who did not achieve normal Uox excretion during the analysis period reached near-normal Uox excretion rates.
  • The mean 24-hour Uox excretion for all 13 participants at Day 180 was in the normal range at 0.44 mmol/1.73 m2 BSA/24 hr.
  • 62% of all participants (8 of 13) demonstrated normalized Uox excretions on at least three consecutive visits, meeting protocol-defined  eligibility for gradual reduction in fluid intake requirements:
    • 70% of participants (7 of 10) with PH1
    • 33% of participants (1 of 3) with PH2
      • The mean maximum reduction in Uox excretion for all participants was 70.9% (range, 54.9% to 87.5%) by Day 180. 

    Nedosiran was generally well tolerated, and no serious safety concerns were identified in this ongoing study. There were no treatment discontinuations or study withdrawals during the observation period. Two participants had serious treatment-emergent adverse events (TEAEs) (pyelonephritis and nephrolithiasis) that were determined by the investigator to be unrelated to nedosiran treatment. The most common TEAEs were mild to moderate administration-site reactions. Protocol-defined injection-site reactions (ISRs) occurred in 18.8% of participants.