Research from the University of Iowa has found an effective treatment for rare kidney diseases in children

Research from the University of Iowa has found an effective treatment for rare kidney diseases in children

A rare and life-threatening kidney disease in children finally has an effective treatment, thanks in large part to groundbreaking research and clinical leadership at the University of Iowa Health Care Stead Family Children’s Hospital.

The disease, known as C3 glomerulopathy (C3G), is an extremely rare condition that primarily affects children and young adults. Only about 5,000 Americans suffer from C3G, which causes progressive kidney damage, with more than half of patients progressing to end-stage kidney failure within a decade of diagnosis.

Unlike previous treatments for C3G, which aimed to alleviate the disease's damaging inflammatory process, the new, first-of-its-kind drug directly targets the root cause of C3G dysfunction in the body's complement system, part of the immune response.

Carla Nester, MD, director of the rare kidney disease clinic at UI Health Care, led the global pediatric clinical trial for the new drug pegcetacoplan. The results were astonishing: the amount of protein in the patients' urine decreased by 68% and kidney function stabilized. Up to 67% of children achieved complete remission and 72% showed no disease activity in their kidney biopsies.

“This is the closest thing to a cure we have ever seen for this disease,” says Nester, a professor of pediatrics at UI Health Care Stead Family Children’s Hospital and senior author of the study published inNew England Journal of Medicineon December 3rd. “We still need to monitor the long-term outcomes of these patients, but the data from this study is absolutely amazing.”

The randomized, double-blind, placebo-controlled phase 3 study was conducted at 122 centers in 19 countries and included 124 patients. Based on the results, pegcetacoplan was approved by the US Food and Drug Administration (FDA) earlier this year as the first treatment for patients aged 12 years and older with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), a closely related rare and serious kidney disease.

A global leader in rare kidney diseases

Over the past few decades, UI Health Care has become a global leader in complement-mediated kidney disease. This latest clinical advance is based on basic research into the complement system led by Richard Smith, MD, UI professor of pediatrics and otolaryngology and an expert in the causes of complement-related kidney disease and hearing loss. This research, combined with Nester's clinical expertise in glomerular diseases, has made Iowa and Stead Family Children's Hospital one of the few centers in the United States capable of providing comprehensive care to C3 glomerulopathy patients, including efficient diagnosis, state-of-the-art management and the opportunity to participate in both basic and clinical research such as the VALIANT trial, which tested pegcetacoplan.

“It’s the combination of research and clinical departments that makes Iowa such a powerhouse,” Nester says. Importantly, the UI team has also earned the trust of patients and families affected by C3G. Patients travel from across the country and around the world to receive treatment at the UI Rare Kidney Disease Clinic.

One of our patients flew in from Qatar to receive treatment at our clinic and another moved from Europe to be under our care. That’s how well known and trusted our program has become.”

Carla Nester, MD, director of the rare kidney disease clinic at UI Health Care

This strong reputation and connection to the patient community enabled UI Health Care to be the largest enrolled center in this global study. To demonstrate the effectiveness of a drug therapy, recruiting sufficient patients for such clinical trials on rare diseases is crucial.

From the bench to the bedside table – and beyond

Research conducted in Smith's laboratory over many years has increased the understanding of the underlying biology of C3G and led to the realization that inhibiting excessive activation of the complement pathway could be the key to effective treatment. Determined to translate this knowledge into therapies for patients, UI researchers worked with pharmaceutical companies to develop and test new drugs that could inhibit complement activation.

Unlike previous treatments that relied on broad anti-inflammatory drugs such as steroids or drugs that targeted the wrong aspect of the complement system, this new class of drugs blocks precisely the faulty part of the complement system.

Pegcetacoplan is administered via twice-weekly injection, which many young patients prefer to daily oral medications. Another new drug called iptacopan, which also inhibits the complement system, was also approved earlier this year to treat adults with C3G. UI Health Care was also the lead global enrollee in this clinical trial that led to the approval of iptacopan.

For patients, the impact of these new drugs is profound. Nester remembers a college student who struggled with the disease and is now in complete remission and thriving in his career, as well as pediatric patients who no longer have to constantly worry about their health and can instead look forward to a normal childhood.

“This is the year we can finally help patients,” says Nester. “It’s been a long road, but we’re here.”

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