FDA Provides Accelerated Approval of First IgA Nephropathy Therapy

The FDA has just announced its accelerated approval of the very first therapy which can reduce proteinuria (high levels of protein in the urine) in patients diagnosed with primary immunoglobulin A (IgA) nephropathy (Berger’s disease). This is fantastic news for this patient population as IgA nephropathy is progressive and can often lead to a patient needing dialysis or even a kidney transplant. This disease-specific therapy could change the lives of many individuals in this population by slowing the decline of the kidneys.

The newly approved therapy is a delayed-release budesonide (Tarpeyo) capsule. It is indicated for patients who are at risk for a fast disease progression (UPCR = 1.5g/g or higher). This therapy is a corticosteroid.

The study (NeflgArd) which led to this approval is described below.

The Study

The NeflgArd study included 199 patients who were diagnosed with IgA nephropathy and who had a reduced kidney function, as well as proteinuria. This study was both randomized and double-blind.

Half of the patients were given a RAS inhibitor and placebo and the other half were given a RAS inhibitor and budesonide.

At 9 months, the researchers found that those assigned to receive 16mg of the delayed release budesonide treatment each day had a 34% reduction of UPCR, which provides an estimate of protein excretion each day. Those in the placebo group only had a 5% reduction.

Following the 9 month period, a 2 week period of tampering commenced for those in the treatment group where the dose was reduced by half.

Something notable was that in all subgroups of patients, the results remained consistent during this trial. That could mean that this treatment may be efficacious and safe for all IgA nephropathy patients.

Steroid

Budesonide is a corticosteroid but it has weak mineralocorticoid activity and potent glucocorticoid activity. The delayed release nature of the capsule allows the treatment to remain encapsulated until it gets to the ileum.

In the ileum, the treatment targets mucosal B cells. One of these targets are the Peyer’s patches, which are the cells responsible for producing galactose-deficient IgA1 antibodies which cause IgA nephropathy.

The most common side effects of this medication, like similar steroids, were muscle spasms, weight gain, hypertension, face edema, acne, dyspepsia, dyspnea, hirsutism, and fatigue. It can also lead to hypercortisolism, immunosuppression, as well as adrenal suppression. Due to these factors, it may not be a good option for those who have liver impairment or any form of infection including viral, parasitic, fungal, bacterial, or tuberculosis.

The company marketing the drug, Calliditas, expects that this treatment will be available by early 2022. That said, due to the accelerated nature of the approval, an ongoing study is required to continue to substantiate the efficacy.

You can read more about this treatment and recent approval here.

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