Immunoglobulin A nephropathy (IgAN) is a kidney disease that occurs when the antibody immunoglobulin A (IgA) builds up in the kidneys. This results in local inflammation that impacts the kidneys’ ability to properly filter waste from the blood, according to the Mayo Clinic.

In a phase III (3) clinical trial, researchers investigated the effects of a pharmaceutical treatment, called Nefecon, on patients with IgAN.* The oral medication was found to impact urine protein-to-creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR)—both indicators of kidney damage.

What they did

Researchers analyzed 199 patients diagnosed with IgAN who were on stable renin-angiotensin system (RAS) treatment or RAS inhibitor therapy. They were split into two groups; one group was given 16 mg of Nefecon, while the other was given a placebo. Participants were treated every day for nine months and assessed for changes in:

• eGFR
• 24-hour urine protein excretion
• Urine albumin-to-creatinine ratio (UACR)

The phase III trial was split into two parts.

Part A included participants over 18 years of age with a total urine protein of ≥ 1g / day, and an eGFR of ≥ 35 mL/min * 1.73m2 and ≤ 90 ml/min * 1.73m2, in addition to RAS treatment and inhibitor therapy. They excluded participants with:

• Secondary forms of IgAN
• Tuberculosis
• Kidney transplant
• Treatment with high dose corticosteroids or immunosuppressants in the past 12 months

Part B was designed to confirm long-term renal protection; it’s a 12-month follow-up after Part A’s completion that is currently an ongoing trial. This trial consists of 360 patients and includes 199 patients from Part A. 

What they found

After analyzing the participants’ 24-hour urine creatinine ratio, researchers found a 31% mean reduction in the group who took the medication versus 5% in those who took the placebo. The reduction occurred after nine months of taking 16 mg of Nefecon, with significant continued improvement at 12 months. 

They also found that eGFR showed a treatment benefit of 7% at the nine-month mark, reflecting stabilization. Meanwhile, participants in the placebo group had a 7% decline in eGFR, reflecting damage. There was a 4.04 ml/min/1.73m2 in the placebo group over nine months compared to a 0.17 ml/min/1.73m2 decline in the treatment group. 

The findings also showed that Nefecon was generally well tolerated and had a safety profile comparable to that of budesonide, the generic version of Nefecon. There were significantly fewer participant withdrawals in phase III than what occurred in phase II (2).

What it means

After nine months’ of taking Nefecon, researchers discovered a significant and beneficial effect on factors that could otherwise lead to the progression of end-stage renal disease (ESRD) for IgAN patients. Oral therapy was tolerated well, too.

Renée Aguiar-Lucander, CEO of Calliditas (the company that is developing Nefecon), expressed, “We are delighted with this strong data set which confirms the results seen in the Phase 2b trial and provides further support for effectively treating IgAN at its origin. This result brings hope to thousands of patients who today have no approved treatment alternatives.”

Calliditas plans to submit for approval with the U.S. Food and Drug Administration (FDA) in 2021.

*Calliditas Therapeutics. (2020, Nov. 9). Calliditas Announces Positive Topline Results from Pivotal Phase 3 NefIgArd Trial. Cision PR Newswire. https://www.prnewswire.com/news-releases/calliditas-announces-positive-topline-results-from-pivotal-phase-3-nefigard-trial-301168379.html