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The FDA granted accelerated approval for the first drug to reduce proteinuria in primary immunoglobulin A (IgA) nephropathy, the .

The delayed released budesonide (Tarpeyo) capsules are indicated to lower increased protein levels in the urine for adults with this rare form of nephropathy, also known as Berger's disease. More specifically, the drug is intended for those at risk of rapid disease progression, typically defined as a urine protein-to-creatinine ratio (UPCR) of 1.5 g/g or higher.

"[IgA nephropathy] is a tough diagnosis for many patients, and it can progressively lead to the need for dialysis and/or kidney transplantation," commented Richard Lafayette, MD, of the Stanford Glomerular Disease Center in California, in a from drugmaker Calliditas Therapeutics' announcement. "The FDA approval of Tarpeyo now offers disease-specific treatment for patients with this complicated disease."

Support for approval comes from the of 199 patients with biopsy-proven IgA nephropathy, reduced kidney function (eGFR ≥35 mL/min/1.73 m²), and proteinuria (≥g/day or UPCR ≥0.8 g/g).

After 9 months, those assigned to receive 16 mg of delayed release budesonide once-daily on top of a stable, maximally tolerated dose of a renin-angiotensin system (RAS) inhibitor saw a 34% reduction in UPCR -- a marker of estimated daily protein excretion -- as compared with only a 5% reduction for those assigned to a RAS inhibitor plus placebo. After 9 months, patients underwent a 2-week tapering period (8 mg budesonide once daily or continued placebo). Beyond meeting the primary endpoint, the study also saw consistent efficacy across all key subgroups.

Acting as a corticosteroid with potent glucocorticoid activity, Calliditas explained that budesonide has weak mineralocorticoid activity that undergoes substantial first pass metabolism. It was designed as an enteric coated 4 mg delayed release capsule that remains intact until it reaches the ileum.

"Each capsule contains coated beads of budesonide that target mucosal B cells present in the ileum, including the Peyer's patches, which are responsible for the production of galactose-deficient IgA1 antibodies causing IgA nephropathy," the company noted.

Because this agent is a corticosteroid, it may cause hypercortisolism and adrenal suppression, which may be magnified in people with moderate-to-severe liver impairment. And since it's also an immunosuppressant, patients with certain infections -- such as tuberculosis, untreated fungal, bacterial, systemic viral or parasitic infections, or ocular herpes simplex -- should not be prescribed the drug.

As expected with a steroid, the most common side effects reported in the trial included hypertension, peripheral and face edema, muscle spasms, acne, dermatitis, weight gain, dyspnea, dyspepsia, fatigue, and hirsutism.

The agency pointed out that because this was an accelerated approval, the developer still must complete an ongoing study to confirm the drug actually slows kidney function decline associated with IgA nephropathy.

Calliditas said it expects the drug to hit U.S. shelves by early 2022.

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