Dicerna Announces Results for PHYOX™4, Single-Dose Study of Nedosiran in Primary Hyperoxaluria Type 3 (PH3)
Oct 19, 2021
– Study Met Primary Safety Endpoint; Nedosiran Shown to be Generally Safe and Well Tolerated in Patients With PH3 –
– Although Trial Did Not Meet Prespecified Secondary Efficacy Endpoint, Data Showed Encouraging Trends in Urinary Oxalate Reduction With Nedosiran Treatment –
– Company on Track to Submit Nedosiran New Drug Application (NDA) to the
“The favorable safety and tolerability results, coupled with the encouraging trends in Uox reduction observed in the first clinical trial of any investigational therapy in patients with PH3, provide important initial data for nedosiran in PH3,” said
The PHYOX4 trial (NCT04555486) was a randomized, placebo-controlled, double-blind, multicenter study evaluating the safety and tolerability of a single subcutaneous dose of nedosiran compared to placebo in patients with PH3 who had at least one kidney stone event in the prior 12 months (nedosiran n=4; placebo n=2). All reported adverse events (AEs) were mild and unrelated to nedosiran treatment. The most commonly reported AE was back pain. No serious AEs were reported in the study.
No subjects in either group achieved the prespecified secondary efficacy endpoint, which was a greater than 30% decrease from baseline in 24-hour Uox excretion on at least two consecutive visits over the three-month observation period. However, all patients administered a single dose of nedosiran demonstrated Uox reductions relative to baseline at one or more time points during the three-month period.
About Primary Hyperoxaluria (PH)
Primary hyperoxaluria (PH) is a family of ultra-rare, life-threatening genetic disorders that initially manifest with complications in the kidneys. There are three known subtypes of PH (PH1, PH2 and PH3), each resulting from a mutation in one of three different genes. These genetic mutations cause enzyme deficiencies that result in the overproduction of oxalate, which is an end-product of metabolism. Excess production and accumulation of oxalate leads to recurrent kidney stones, nephrocalcinosis and chronic kidney disease that may progress to end-stage renal disease requiring intensive dialysis. Compromised renal function eventually results in the accumulation of oxalate in a wide range of organs including the skin, bones, eyes and heart. In the most severe cases, symptoms start in the first year of life. A combined liver-kidney transplant may be undertaken to resolve PH1 or PH2, but it is an invasive solution with limited availability and high morbidity that requires lifelong immune suppression to prevent organ rejection. Genetic studies suggest approximately 8,500 people in the
Nedosiran is in development for the treatment of primary hyperoxaluria (PH) as part of the PHYOX clinical development program and is Dicerna’s most advanced RNAi drug candidate utilizing our proprietary GalXC RNAi technology. Nedosiran is designed to inhibit production of the hepatic lactate dehydrogenase (LDH) enzyme – an enzyme that catalyzes the final step in the glyoxylate metabolism pathway that can lead to oxalate overproduction in patients with PH.
Cautionary Note on Forward-Looking Statements
This press release includes forward-looking statements. Such forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Examples of forward-looking statements include, among others, statements we make regarding our product candidates and the development thereof, such as the Company’s PHYOX clinical development program for nedosiran in PH; the impact of the results from the PHYOX4 trial of nedosiran for the potential treatment of PH3, including any further analysis of the results, as well as its potential impact on the broader PHYOX clinical development program; the therapeutic potential of our product candidates, such as nedosiran; the Company’s refined near-term nedosiran strategy to focus primarily on the treatment of PH1; the Company’s regulatory plans and timelines for nedosiran, including our planned submission of an NDA to the FDA for nedosiran for the treatment of PH1; our business and operations, including the discovery, development and commercialization of our product candidates and technology platform, and the therapeutic potential thereof; our collaboration with partners and any potential future collaborations.
The process by which investigational therapies, such as nedosiran, could potentially lead to an approved product is long and subject to highly significant risks. Applicable risks and uncertainties include those relating to Dicerna’s clinical research and other risks identified under the heading "Risk Factors" included in the Company’s most recent filings on Forms 10-K and 10-Q and in other future filings with the
1 Hopp K, et al. J Am Soc Nephrol. 2015;26(10):2559-2570 and