Nedosiran in primary hyperoxaluria subtype 3: results from a phase I, single-dose study (PHYOX4)

Goldfarb, David S.; Lieske, John C.; Groothoff, Jaap W.; Schalk, Gesa; Russell, Kerry; Yu, Shiwen; Vrhnjak, Blaz

doi:10.1007/s00240-023-01453-3

Cited by 15 publications

(10 citation statements)

References 23 publications

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“…Approximately 27% of the administered nedosiran dose is excreted unchanged into the urine within 24 h of administration [ 7 ]. Nedosiran exposure in patients with PH3 is generally similar to that in those with PH1 or PH2 [ 13 ].…”

Section: Scientific Summarymentioning

confidence: 99%

Nedosiran: First Approval

Syed

2023

Drugs

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Nedosiran (RIVFLOZA™), a once-monthly subcutaneous small interfering RNA (siRNA) therapy, is being developed by Dicerna Pharmaceuticals, a Novo Nordisk company, for the treatment of primary hyperoxaluria (PH). It reduces oxalate overproduction by inhibiting the expression of the hepatic lactate dehydrogenase (LDH) enzyme. Nedosiran received its first approval on 29 September 2023 in the USA to lower urinary oxalate levels in children aged ≥ 9 years and adults with PH type 1 (PH1) and relatively preserved kidney function [e.g. estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m 2 ]. This article summarizes the milestones in the development of nedosiran leading to this first approval for PH1. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-023-01976-4.

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Section: Scientific Summarymentioning

confidence: 99%

Nedosiran: First Approval

Syed

2023

Drugs

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“…This therapy has been approved for treating primary hyperoxaluria type 1 (PH1) in adults and high oxalate levels in children aged 9 years and older. Studies have shown that nedosiran injections effectively lower 24-h urinary oxalate compared to placebo (Baum et al 2023 ; Goldfarb et al 2023 ). The therapy has proven to be well-tolerated and safe, with injection site reactions reported as the only common AE effects.…”

Section: Renal and Gastrointestinal Disordersmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2023

Kayki-Mutlu,

Aksoyalp,

Wojnowski

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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With 54 new drugs and seven cellular and gene therapy products, the approvals by the US Food and Drug Administration (FDA) recovered 2023 from the 2022 dent back to the levels of 2020–2021. As in previous years of this annual review, we assign these new drugs to one of three levels of innovation: first drug against a condition (“first-in-indication”), first drug using a novel molecular mechanism (“first-in-class”), and “next-in-class,” i.e., a drug using an already exploited molecular mechanism. We identify four (7%) “first-in-indication,” 22 (36%) “first-in-class,” and 35 (57%) “next-in-class” drugs. By treatment area, rare diseases (54%) and cancer drugs (23%) were once again the most prevalent (and partly overlapping) therapeutic areas. Other continuing trends were the use of accelerated regulatory approval pathways and the reliance on biopharmaceuticals (biologics). 2023 marks the approval of a first therapy based on CRISPR/Cas9 gene editing.

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“…Treatments of PH3 that have been tested include substrate reduction therapy to target enzymes responsible production for oxalate with RNA interference (RNAi) (targeting LDH with Nedosiran) and CRISPR (targeting LDH) and enhanced intestinal oxalate degradation using probiotics (Oxalobacter formigenes) or enzymes (oxalate decarboxylase) ( Milliner et al, 2018 ; Lingeman et al, 2019 ; Quintero et al, 2020 ; Martinez-Turrillas et al, 2022 ; Goldfarb et al, 2023 ).…”

Section: Genetic Causes Of Nephrolithiasis and Nephrocalcinosis In Ch...mentioning

confidence: 99%

Review of childhood genetic nephrolithiasis and nephrocalcinosis

Gefen,

Zaritsky

2024

Front. Genet.

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Nephrolithiasis (NL) is a common condition worldwide. The incidence of NL and nephrocalcinosis (NC) has been increasing, along with their associated morbidity and economic burden. The etiology of NL and NC is multifactorial and includes both environmental components and genetic components, with multiple studies showing high heritability. Causative gene variants have been detected in up to 32% of children with NL and NC. Children with NL and NC are genotypically heterogenous, but often phenotypically relatively homogenous, and there are subsequently little data on the predictors of genetic childhood NL and NC. Most genetic diseases associated with NL and NC are secondary to hypercalciuria, including those secondary to hypercalcemia, renal phosphate wasting, renal magnesium wasting, distal renal tubular acidosis (RTA), proximal tubulopathies, mixed or variable tubulopathies, Bartter syndrome, hyperaldosteronism and pseudohyperaldosteronism, and hyperparathyroidism and hypoparathyroidism. The remaining minority of genetic diseases associated with NL and NC are secondary to hyperoxaluria, cystinuria, hyperuricosuria, xanthinuria, other metabolic disorders, and multifactorial etiologies. Genome-wide association studies (GWAS) in adults have identified multiple polygenic traits associated with NL and NC, often involving genes that are involved in calcium, phosphorus, magnesium, and vitamin D homeostasis. Compared to adults, there is a relative paucity of studies in children with NL and NC. This review aims to focus on the genetic component of NL and NC in children.

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Nedosiran in primary hyperoxaluria subtype 3: results from a phase I, single-dose study (PHYOX4)

Cited by 15 publications

References 23 publications

Nedosiran: First Approval

Nedosiran: First Approval

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2023

Review of childhood genetic nephrolithiasis and nephrocalcinosis

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