FDA grants Rare Pediatric Disease Designation to META-001-PH to treat primary hyperoxaluria

FDA grants Rare Pediatric Disease Designatjion to META-001-PH to treat primary hyperoxaluria | Image Credit: © Araki Illustrations- © Araki Illustrations - stock.adobe.com.

META-001-PH, an investinal new drug from META Pharmaceuticals for the treatment of primary hyperoxaluria (PH), has been granted Rare Pediatric Disease Designation (RPDD) by the FDA.¹

META's small molecule drug, based on preclinical experiments in animal disease models, can reduce urinary oxalate excretion by up to 80%, while having demonstrated tolerability and safety in these models, META stated in a press release. The treatment is undergoing IND-enabling toxicity studies, while a clinical phase 1 safety assessment in healthy individuals is planned for the first half of 2025.¹

The orally-administered, once-daily META-001-PH can "maintain oxalate at normal levels, thus demonstrating the potential for better long-term control of kidney stone formation in patients with PH," META said in a statement.

RPDD is an eligibility determination for rare pediatric diseases that affect less than 200,000 patients while posing a serious, life-threatening risk to children under 18 years of age. Through the RPDD and Priority Review Voucher (PRV) program, a sponsor who receives an approval for a drug or biological product for a rare pediatric disease may qualify for a voucher that can be redeemed to receive priority review for a different product, according to the FDA. Sponsors are eligible to receive a PRV upon approval of a New Drug Application (NDA) or Biologics License Application (BLA) for a rare pediatric disease.^1,2

PH, an autosomal recessive metabolic disorder, results in the overproduction of oxalate that is deposited in the body because of defects in enzymes responsible for oxalate metabolism in the liver and other organs. Generally, patients present with kidney stones, nephrocalcinosis, renal failure, and oxalate deposition in other organs, with severe cases potentially leading to end-stage renal disease, kidney transplantation, or combined liver-kidney transplantation.¹

Differentiated by the specific enzyme that is deficient, there are 3 main types of PH:³

• PH I - caused by mutations in the AGXT gene
• PH II - caused by mutations in the GRHPR gene
• PH III - Caused by mutations in the HOGA1 gene

Symptom onset typically begins between 0 to 3 years of age, and without intervention, patients will likely develop end-stage renal disease during adolescence, severely threatening their lives. According to META, PH incidence is estimated to be 1 in 58,000, leading to more than 10,000 people affected in the United States and European Union, and more than 20,000 people in China, with no current cure.¹ According to the National Organization for Rare Diseases (NORD), exact incidence and prevalence of PH is unknown, noting that one estimate places PH type 1 prevalence at 1 to 3 cases per 1,000,000 people in the general population, with fewer than 1000 individuals affected in the United States and 1 case per 120,000 live births per year in Eurpoe.³

Current treatment is primarily supportive care consisting of increased fluid intake to dilute oxalate in the urine, along with pyridoxine—or vitamin B6—to reduce oxalate production.¹ What's more, treatment could require the coordinated efforts of a multidisciplinary team consisting of pediatricians, surgeons, nephrologists, hepatologists, urologists, dietitians, and other professionals who may need to systematically plan an affected child's care.^1,3

NORD states specific therapeutic procedures and interventions can vary based on several factors such as specific disease subtype, disease stage, responsiveness to pyridoxine, age and general health of the individual and other elements. Prompt diagnosis and early therapy are essential to slow progression of the disorder and preserve kidney function for as long as possible.³

References:

1. META Pharmaceuticals announces FDA grants Rare Pediatric Disease Designation to META-001-PH for the treatment of primary hyperoxaluria. META Pharmaceuticals. Press release. August 5, 2024. Accessed August 6, 2024. https://www.prnewswire.com/news-releases/meta-pharmaceuticals-announces-fda-grants-rare-pediatric-disease-designation-to-meta-001-ph-for-the-treatment-of-primary-hyperoxaluria-302214393.html
2. Rare Pediatric Disease Designation and Priority Review Voucher programs. FDA. Updated May 28, 2024. Accessed August 6, 2024. https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/rare-pediatric-disease-designation-and-priority-review-voucher-programs
3. Primary hyperoxaluria. National Organization for Rare Disorders. Updated January 23, 2024. Accessed August 6, 2024. https://rarediseases.org/rare-diseases/primary-hyperoxaluria/#causes