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Understanding Atrasentan (Vanrafia) for IgA Nephropathy, with Richard Lafayette, MD
Lafayette describes ongoing unmet needs in IgAN care and how the growing understanding of disease pathogenesis has informed drug development.
Just a few years ago, there were no US Food and Drug Administration (FDA)-approved treatments for IgA nephropathy (IgAN), leaving nephrologists with limited options to offer their patients. Now, with a growing understanding of the disease’s pathogenesis and progression, a wave of targeted treatments has transformed the landscape, ushering in a new era of disease-specific care.
Most recently, the FDA granted accelerated approval to Novartis’ atrasentan (Vanrafia), a once-daily, non-steroidal, oral treatment, for reducing proteinuria in adults with primary IgAN at risk of rapid disease progression based on a prespecified interim analysis of 36-week data from the ongoing phase 3 ALIGN trial. Of note, the decision marked the FDA’s first approval for a selective endothelin A receptor antagonist for reducing proteinuria in IgAN.
“We've learned to really think about the different pathogenesis causes as a way to bring in new therapies such as complement blockade and blocking endothelin, and I think we're starting to exercise those muscles very well and learn how to use these medications, either individually or as combination therapy,” Richard Lafayette, MD, a professor of medicine and director of the Glomerular Disease Center at Stanford University Medical Center, explained to HCPLive. “With more and more drug approvals, including this recent accelerated approval, we have more medications, but there are still patients who have high grade proteinuria after therapy, patients where we still see their GFR declining, their kidney function failing, and having more options and tools is really incredibly important still.”
Lafayette notes that while systemic corticosteroids and immunosuppression may be helpful in certain patient populations, they are often associated with toxicity, can only be given for short periods of time, and have short-term benefits, underscoring the need for other therapies to offer patients.
“When we look at the pathogenesis of IgA nephropathy, we really can look at upstream events and downstream events, and upstream events are the formation of antibodies and the deposition of immune complexes in the kidney. But once the kidney has immune complexes, it can do quite well,” Lafayette explained, describing the role that upregulation of endothelin plays in response to those immune complexes.
He goes on to explain how endothelin, particularly endothelin A, is implicated not only in vasoconstriction, but also in kidney inflammation and scarring, making it an attractive therapeutic target. Lafayette describes having atrasentan, an endothelin A receptor antagonist, as “great news,” citing its safety and efficacy in part A of the ALIGN trial, which is awaiting full 2-year data.
“The agency looks at the totality of the data to say that this can actually positively impact our at-risk patients, and that's why they gave it accelerated approval,” Lafayette concluded.
Editors’ note: Relevant disclosures for Lafayette include Aurinia, Callidatas, Complexa, Mallinckrodt, Omeros, Pfizer, and others.
