Investigating RNAi therapies for rare and common diseases
We are developing a pipeline of RNAi therapies that aim to restore health by addressing the underlying causes of disease. We currently have three core programs in clinical development:
- PHYOX™ Clinical Program: evaluating nedosiran for the treatment of primary hyperoxaluria (PH)
- Hepatitis B Virus (HBV) Infection: in collaboration with Roche, evaluating RG6346 for the treatment of patients with non-cirrhotic chronic HBV infection
- SHINE Clinical Program: developing belcesiran (DCR-A1AT) for the treatment of patients with alpha-1 antitrypsin (AAT) deficiency-associated liver disease (AATLD)
PHYOX1 (NCT03392896) is a study of nedosiran in healthy volunteers (HVs) and patients with PH1 or PH2. Results from the PHYOX1 clinical trial showed favorable safety and tolerability profiles and normalization or near-normalization of urinary oxalate levels in a majority of participants with PH after a single dose of nedosiran.
PHYOX2 (NCT03847909) is Dicerna’s global, multicenter, double-blind, randomized, placebo-controlled pivotal trial designed to evaluate the efficacy and safety of nedosiran delivered as a once-monthly subcutaneous injection over six months in 35 participants aged six years and older with PH1 or PH2.
In August 2021, we announced positive interim data that showed the nedosiran treatment group demonstrated a statistically significant reduction from baseline in urinary oxalate (Uox) excretion compared to those in the placebo group (p<0.0001). In addition, a significantly higher proportion of patients given nedosiran achieved normal or near-normal Uox at two or more consecutive visits during the last three months of the trial compared to those given placebo (p=0.0025). Uox reductions were significant in participants with PH1 while participants with PH2 showed inconsistent results in this trial. Nedosiran was generally well tolerated in the study with an overall adverse event profile consistent with previously reported data from PHYOX trials.
PHYOX3 (NCT04042402) is a long-term, multidose, open-label, extension trial designed to further evaluate the safety and efficacy of nedosiran. Participants who complete PHYOX trials, and their siblings with PH, are eligible to enroll in the PHYOX3 trial.
In October 2020, we announced positive interim data from the ongoing PHYOX3 trial, which showed normalization or near normalization of urinary oxalate levels in all 13 participants receiving nedosiran who had previously completed the PHYOX1 Phase 1 trial and had reached Day 180 in the ongoing PHYOX3 trial. 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.
PHYOX4 (NCT04555486) is a randomized, placebo-controlled, double-blind, multicenter study designed to evaluate the safety and tolerability of a single subcutaneous dose of nedosiran in patients with PH3 who have had at least one kidney stone event in the last 12 months.
PHYOX7 (NCT04580420) is an open-label, repeat-dose study of nedosiran in participants with PH1 or PH2 who have severe renal impairment, and who may or may not be undergoing dialysis.
PHYOX8 is a study to evaluate patients up to six years of age with PH1 or PH2.
We are collaborating with Roche to develop RG6346 for the treatment of patients with chronic HBV. We initiated a randomized, placebo-controlled Phase 1 clinical trial designed to evaluate the safety and tolerability of RG6346 in healthy volunteers and in patients with non-cirrhotic chronic HBV, which is ongoing. Roche initiated RG6346 in a Roche-sponsored Phase 2 combination trial for the treatment of HBV in March 2021.
We are investigating belcesiran (DCR-A1AT) as part of the SHINE clinical development program. Our Phase 1 trial of belcesiran is an ongoing placebo-controlled study designed to evaluate the safety and tolerability of single doses of belcesiran when administered to healthy adult participants. SHINE includes a Phase 2 study called ESTRELLA, which was initiated in 2021 to evaluate belcesiran in adults with AAT deficiency-associated liver disease (AATLD).