RARE Daily

Dicerna Receives Rare Pediatric Disease Designation for Nedosiran for the Treatment of Primary Hyperoxaluria

June 18, 2020

Rare Daily Staff

The U.S. Food and Drug Administration granted rare pediatric disease designation for Dicerna Pharmaceuticals’ nedosiran, an experimental RNAi therapy being developed as a once-monthly treatment for primary hyperoxaluria.

Primary hypeoxaluria (PH) is a family of ultra-rare, life-threatening genetic disorders that cause 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 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 results eventually in the accumulation of oxalate in organs ranging from skin, bones, eyes, and heart. In the most severe cases, symptoms start in the first year of life.

Liver-kidney transplantation 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. Currently, there is no approved therapy for the treatment of PH. Patients are limited to using hyper-hydration and medication to attempt to increase solubility of oxalate in urine. Despite these interventions, oxalate may continue to accumulate in the kidneys, causing damage.

Dicerna’s lead product candidate nedosiran is the only RNAi therapeutic in development for all three types of PH. Nedosiran is designed to inhibit the lactate dehydrogenase enzyme—an enzyme that catalyzes the final step in a common pathway resulting in oxalate overproduction in PH patients. 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.

The FDA grants Rare Pediatric Disease designation for serious or life-threatening diseases with manifestations in individuals aged from birth to 18 years, including access to the FDA’s expedited review and approval process. The designation makes nedosiran eligible for a Rare Pediatric Disease Priority Review voucher upon approval of the therapy by the FDA.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Sarepta sold its priority review voucher to Vifor Pharma $111 million in February 2020.

“The FDA’s Rare Pediatric Disease designation for nedosiran for primary hyperoxaluria reflects the agency’s continued recognition that PH is a serious and potentially fatal condition, with disease consequences that frequently manifest in childhood but progress over time into adulthood,” said Ralf Rosskamp, chief medical officer at Dicerna. “These patients and their caregivers cope with burdensome and inadequate disease management techniques that ultimately cannot cure their underlying disease or prevent its potential to result in kidney stones, nephrocalcinosis, growth failure and failure to thrive, systemic oxalosis and end-stage renal disease – serious manifestations that often affect children.”

Photo: Ralf Rosskamp, chief medical officer at Dicerna

Editor’s note: This story was updated to correct the most recent sales of a priority review voucher.


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