Benzinga | Oct 22, 2020 10:09AM EDT

Dicerna Pharma Reports New Interim Data From PHYOX 3 Long-Term, Open-Label Extension Study Of Nedosiran For Treatment Of Primary Hyperoxaluria: All Participants Achieved Normalization Or Near-Normalization Of Urinary Oxalate

Dicerna Pharmaceuticals, Inc. (NASDAQ:DRNA) (the "Company" or "Dicerna"), a leading developer of investigational ribonucleic acid interference (RNAi) therapeutics, today announced positive new interim data from its ongoing PHYOX(tm)3 open-label trial of once-monthly nedosiran, an investigational candidate in development for the 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. These results were presented as part of the American Society of Nephrology's Kidney Week 2020 annual scientific conference.

All 13 participants (10 with PH1 and three with PH2) receiving nedosiran, who had previously completed the PHYOX1 Phase 1 trial and had reached Day 180 in the ongoing PHYOX3 trial, achieved normal (12 of 13) or near-normal (one of 13) urinary oxalate (Uox) excretions at one or more timepoints. Of these, all 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. In this study, normal Uox excretions were defined as below 0.46 mmol/1.73m2 body surface area (BSA)/24 hr, and near-normal Uox excretions were defined as ranging from 0.46 to < 0.6 mmol/1.73m2 BSA/24 hr.

"For patients with PH, excessive oxalate production compromises kidney function and can have life-threatening consequences," said Shreeram Aradhye, M.D., executive vice president and chief medical officer at Dicerna. "We are encouraged by this latest interim analysis from our ongoing PHYOX3 trial showing that all PH1 and PH2 participants receiving nedosiran for six months reached the desired ranges of normal or near-normal urinary oxalate excretions. This is a promising outcome suggesting that nedosiran may meaningfully reduce hepatic oxalate overproduction, potentially slowing disease progression. We look forward to additional results from our ongoing PHYOX clinical development program, including our pivotal PHYOX2 trial, to support our planned New Drug Application submission next year."

Key results from the interim analysis:

* 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.

Also presented at ASN Kidney Week were the results of a retrospective claims analysis of commercial plan data (excluding Medicare and Medicaid lives) from IQVIA PharMetrics(r) Plus (1/2014-12/2019). The analysis included a 5:1 ratio of a random 5% sample of patients without PH or secondary hyperoxaluria (SH), matched to patients diagnosed with PH (subtype specificity not available). This analysis showed that the median cost of care for patients with PH (n=324) was approximately seven times higher than patients who did not have PH (n=1,620) (p<0.001).

"The observations from this claims analysis highlight some of the higher health care costs associated with having PH," said Thomas Koenig, vice president, global market access at Dicerna. "This analysis suggests that, even excluding patients who are on Medicare and Medicaid who may have more advanced disease, patients with PH bear higher healthcare-related costs while still facing the potential for chronic kidney stones, declining kidney health, systemic oxalosis impacting other organs and the possibility of end-stage renal disease that may require dual liver-kidney transplantation. This analysis is the first known published insight into healthcare costs associated with PH and emphasizes the need for more research into the clinical and cost burden associated with this disease."

Both posters were presented during the "Genetic Diseases of the Kidneys: Non-Cystic -- 1" session at the Kidney Week conference and will be posted in the Events & Presentations section of Dicerna's corporate website.