FDA Grants Orphan Drug Status to Regulus Therapeutics' Treatment for Common Type of PKD

Regulus Therapeutics announced today FDA has granted the company orphan drug designation for RGLS4326, an investigational therapy being studied to treat autosomal dominant polycystic kidney disease (ADPKD), the most common type of a group of genetic disorders that lead to end-stage renal disease, morbidity, and early death.

ADPKD is caused by mutations in the PKD1 or PDK2 genes. If one parent has the disease, each child has a 50% chance of inheriting it; this form accounts for 90% of the cases.

Other cases are caused by autosomal recessive PKD, when mutations are inherited from both parents who do not have the disease. Both parents must be carrying the mutation but neither may be aware of it. Each child may have a 25% chance of developing PKD.

Although the name suggests the disease affects only the kidneys, development of fluid-filled cysts can spread to the liver, the pancreas, and other organs. While a healthy kidney is about the size of a fist, a kidney filled with cysts from PKD can grow to be about the size of a football weigh up to 30 pounds. Patients with PKD also experience heart valve problems, hypertension, urinary tract infections, colon problems, and significant pain. They can suffer brain aneurysms or strokes. An estimated 500,000 people have PKD.

The investigational therapy, RGLS4326, is a novel oligonucleotide that inhibits miR-17, a microRNA precursor family; the therapy is designed to preferentially target the kidney. Preclinical studies demonstrated an ability to directly regulate PKD1 and PKD2, reducing cyst growth in both human and in vitro ADPKD models. Early work has shown an ability the reduce the spread of cysts and improve kidney function in mice.

Last week, the company announced it had completed a dosing study in healthy volunteers. It is beginning a phase 1b study in patients with ADPKD to study short-term treatment with the study drug to examine safety, tolerability, pharmacokinetics, and changes in disease biomarkers.

The drug’s Investigational New Drug application is on partial clinical hold with FDA, until a second set of requirements have been met.

"This is an important milestone for our APDKD program and our efforts to address the significant unmet medical needs with this disease,” Jay Hagan, CEO of Regulus, said in a statement.