Dicerna Announces Dosing Completion in Nedosiran PHYOX™4 Clinical Trial for Treatment of Primary Hyperoxaluria Type 3
Jun 16, 2021
– Company Continues to Expect Nedosiran New Drug Application Submission in Fourth Quarter of 2021 –
“Meaningful progress has been made in the last two years to better understand the burden of disease for patients with PH,” said
The PHYOX4 trial (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 six patients with PH3 who have had at least one kidney stone event in the last 12 months. The study will also assess the proportion of participants achieving more than a 30% decrease from baseline in 24-hour urinary oxalate (Uox) on two consecutive visits. PHYOX4 participants who respond to treatment with nedosiran and complete the trial are also eligible to enroll in the Company’s PHYOX3 open-label extension study evaluating nedosiran’s long-term safety and efficacy in participants with PH1, PH2 or PH3.
PHYOX4 is part of the broader PHYOX clinical trial program designed to evaluate nedosiran in patients with PH1, PH2 and PH3. Data from PHYOX1, a single-dose Phase 1 trial in healthy volunteers and patients with PH1 or PH2; PHYOX2, the pivotal, double-blind, placebo-controlled, six-month trial in patients with PH1 or PH2; PHYOX4; and the ongoing PHYOX3 study are expected to support the nedosiran New Drug Application (NDA) submission, which is planned for the fourth quarter of 2021.
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 types 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 a substrate called oxalate. Abnormal 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 the only RNAi drug candidate in development for primary hyperoxaluria (PH) types 1, 2 and 3 and is Dicerna’s most advanced product candidate utilizing the proprietary GalXC™ RNAi technology platform. 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 PH1, PH2 or PH3. Dicerna is evaluating the safety and efficacy of nedosiran in patients with all known forms of PH as part of its PHYOX™ clinical development program.
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, including the progress of the Company’s PHYOX4 trial and other trials of nedosiran, results from future trials of the Company’s PHYOX clinical development program, the therapeutic potential of our product candidates, including nedosiran, the planned submission of the New Drug Application (NDA) for nedosiran, as well as to 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
GalXC™, GalXC-Plus™ and PHYOX™ are trademarks of
1 Martin-Higueras, et al. Systemic Oxalosis in Primary Hyperoxaluria Type 3 – Are the Patients at Risk? Nephrology Dialysis Transplantation 36 (Supplement 1): i142–i146, 2021 10.1093/ndt/qfab107. Mini-Oral Presentation at ERA-EDTA 2021
2 Hopp K, et al. J Am Soc Nephrol. 2015;26(10):2559-2570 and