Understanding Primary Hyperoxaluria Type 1 (PH1)
Primary Hyperoxaluria Type 1 (PH1) is an ultra-rare, inherited disorder caused by a genetic mutation leading to a deficiency of the liver enzyme alanine-glyoxylate aminotransferase (AGT). This deficiency causes a buildup of glyoxylate, which is then converted into excessive oxalate by hepatic lactate dehydrogenase (LDH). This excess oxalate forms calcium oxalate crystals and kidney stones, potentially leading to kidney damage, kidney failure, and systemic oxalosis.
The Targeted Action of Rivfloza®
Rivfloza® (nedosiran) is an RNA interference (RNAi) therapy that targets the metabolic defect in PH1.
How RNAi Therapy Works
Rivfloza® uses small interfering RNA (siRNA) to specifically silence the messenger RNA (mRNA) that produces the hepatic lactate dehydrogenase (LDH) enzyme in liver cells. This targeting is facilitated by N-acetyl-D-galactosamine (GalNAc). By reducing LDH, Rivfloza® blocks the final step in oxalate production, leading to lower urinary oxalate levels and potentially reducing crystal and stone formation.
Administration
Rivfloza® is a subcutaneous injection given once a month. The dosage is based on the patient's weight. Patients or caregivers can be trained to administer the injection at home.
Clinical Trial Results and Efficacy
FDA approval for Rivfloza® is based on clinical trials like PHYOX2 and the PHYOX3 extension study. PHYOX2 showed a significant reduction in 24-hour urinary oxalate (Uox) excretion in Rivfloza® treated patients. In patients aged 9 and older, Rivfloza® resulted in a 56% greater reduction in Uox compared to placebo. The PHYOX8 study in pediatric patients aged 2 to <12 years showed an average 64% reduction in spot urinary oxalate:creatinine ratio after six months. Long-term data from PHYOX3 suggest sustained Uox reduction with ongoing treatment.
Rivfloza® vs. Oxlumo®: A Comparison
Both Rivfloza® and Oxlumo® (lumasiran) are FDA-approved RNAi therapies for PH1. They differ in target, administration, and approved age ranges:
| Feature | Rivfloza® (nedosiran) | Oxlumo® (lumasiran) |
|---|---|---|
| Mechanism of Action | Silences the LDHA gene, which codes for the hepatic lactate dehydrogenase (LDH) enzyme. | Silences the HAO1 gene, which codes for the glycolate oxidase (GO) enzyme. |
| Administration Frequency | Once-monthly subcutaneous injection. | Monthly for the first three months, then once every three months for patients over 10 kg. |
| Administration Method | Can be self-administered by patients aged 12+ or a caregiver after training. | Typically administered by a healthcare professional. |
| Approved Age Range | Aged 2 years and older with relatively preserved kidney function. | Approved for all ages, including infants, with no kidney function restriction. |
Side Effects and Safety Profile
Rivfloza® is generally well-tolerated. The most common side effects are mild injection site reactions like redness, pain, bruising, and rash. Serious allergic reactions are possible but uncommon, presenting with symptoms like rapid heart rate, swelling, hives, or breathing difficulties, requiring immediate medical attention.
Conclusion: A New Frontier in PH1 Treatment
Rivfloza® is a significant advance for primary hyperoxaluria type 1. This targeted, once-monthly therapy, potentially administered at home, offers a new option for patients. By addressing oxalate overproduction in the liver, it can reduce kidney stone formation and slow kidney damage progression. Clinical trial efficacy in adults and children makes Rivfloza® a valuable addition to PH1 treatment strategies.
For more detailed prescribing information, consult the Rivfloza official website.
