People with IgA nephropathy could have two new medication options for treating their kidney disease in the coming years, after two early-stage clinical trials have shown promising results in small groups of patients. Notably, the studies of the drugs – felzartamab and atacicept – have shown benefits in different ways.
IgA nephropathy is a type of kidney disease that happens when the immune system creates autoantibodies, which are molecules that mistakenly attack a person’s own body and cause damage to the kidneys and other areas. It can be managed with drugs that generally suppress the immune system, but these can involve dangerous side effects. Therefore, researchers have been exploring more targeted therapies that only suppress certain immune cells that contribute to IgA nephropathy, rather than the entire immune system.
One of these targeted therapies, felzartamab, works by targeting a type of immune cell called the plasma cell. Felzartamab has been used to treat other diseases involving abnormal plasma cells, which prompted researchers to test whether it would also be effective in people with IgA nephropathy.
In a phase II clinical trial that took place across multiple countries, 54 people with IgA nephropathy were given various doses of felzartamab, or a placebo. Patients who received the most doses of felzartamab – nine doses over a six-month period – experienced the most benefits, which included substantially reduced levels of harmful autoantibodies, as well as a significant reduction in protein in their urine (indicating a reduction in kidney damage). These preliminary results, published in Kidney International, suggest that felzartamab may be effective at suppressing patients’ disease.
Dr. Sean Barbour is an IgA nephropathy expert with the University of British Columbia who helped analyze the data. What was particularly striking about the results, he says, is that felzartamab showed benefits even after the patients stopped receiving their last dose – up to 18 months after.
“That gives some hope that one treatment course could produce sustained benefits in terms of controlling patients’ disease,” Barbour explains.
Based on these findings, the international team of researchers are launching a larger, phase III clinical trial in more patients, and Barbour will be leading part of that study in British Columbia.
In a separate clinical trial, Barbour and his colleagues tested atacicept, which targets a different kind of immune cell involved in IgA nephropathy, called a B cell. Patients who were initially given the drug for 36 weeks, to explore which dosages were safe and recommended, were given the option to continue taking the drug for an additional 60 weeks. More than 110 patients chose to continue taking the therapy.
The results, published in the Journal of the American Society of Nephrology, were striking. Whereas many people with IgA nephropathy are at high risk of kidney function decline, patients taking atacicept experienced very little reduction in kidney function over the course of the study.
“The early data suggest this drug is very beneficial in this population, slowing kidney function decline rates towards what you would expect with normal aging,” Barbour says.
He notes both drugs provide exciting advances for the potential treatment of IgA nephropathy, but for different reasons. “One is the sustained benefit of felzartamab. The other is the magnitude of benefit that has been seen with atacicept,” he says.
Barbour is looking forward to the results of larger clinical trials of both medications, which could pave the way for regulatory approval.
