Dana Rizk, M.D., professor of Medicine in the Division of Nephrology, has been named the latest recipient of the school’s Featured Discovery award. This recognition celebrates notable research contributions made by faculty and highlights the impact of their scientific advancements.
Rizk’s study, “Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy, " was published in The New England Journal of Medicine.
IgA nephropathy (IgAN) is a rare condition that causes notable kidney damage when one’s immune system produces antibodies inside the kidneys. Rizk explained, “IgA nephropathy is the most common glomerulonephritis worldwide. The disease is associated with a significant lifetime risk of progression to end-stage kidney disease and subsequent increased mortality.”
Risk explained, “In this phase 3, double-blind, randomized, placebo-controlled trial, adults with biopsy-confirmed IgAN and significant proteinuria were randomly assigned, in a 1:1 ratio, to receive oral iptacopan (200 mg) or placebo twice daily for 24 months. Iptacopan is an oral factor B inhibitor that can selectively block the alternative complement cascade.”
The research and trial noted that “treatment with iptacopan resulted in a significant and clinically meaningful reduction in proteinuria compared to placebo. It has been established that proteinuria reduction in IgAN translates into the preservation of kidney function long term.” The results of Rizk and her team's work conclude that iptacopan will improve the overall prognosis of IgAN patients and delay adverse kidney outcomes.
What compelled you to pursue this research?
For the last 15 years or so of my career, I have been interested in glomerular diseases. These are rare kidney disorders, often autoimmune in nature, which typically affect young patients. IgAN is the most common among these rare diseases. Our team at UAB has long been spearheading translational research efforts elucidating the disease pathogenesis. There has recently been a significant global effort to test new therapeutics for the management of IgAN. We at UAB have been actively participating in and leading these efforts. Knowing that we could meaningfully contribute to these therapeutic trials that would ultimately change the lives of patients suffering from IgAN compelled me to pursue this research.
How do you feel your research will impact the science community?
This is the first trial in IgAN to test the benefit of a complement inhibitor in the disease treatment. Biomarker data collected during this trial will allow us to understand better the role of complement activation in the disease pathogenesis and severity. This trial will pave the way for other therapeutics that can inhibit the complement system at different levels to be considered. Additionally, in the future, we might explore the potential use of iptacopan in combination with other immunosuppressives to treat aggressive presentations of IgAN disease. This trial also unveils the value of complement inhibitors in managing other rare glomerular diseases that may be complement-mediated.
What is your research’s relevance to human disease?
This pivotal phase 3 clinical trial led to the accelerated approval of Fabhalta (iptacopan) for treating IgAN patients at high risk of disease progression. Knowing that people living with this chronic, incurable disease now have potential options that might positively impact their outcomes makes this research very relevant.
How has being at UAB and living in Birmingham affected your research?
Coming to UAB in 2008 allowed me to pursue my interest in glomerular diseases. The UAB team, with Bruce A. Julian, M.D., and Jan Novak, Ph.D., at the helm, had already established itself as leaders in basic and translational research elucidating IgAN pathogenesis. They welcomed me into the team, and together we expanded our scope. In parallel, I established the dedicated Glomerular Kidney Disease Clinic at the Kirklin clinic, focusing on managing patients with these rare kidney diseases holistically. Our Glomerular Disease Clinic serves patients from within Alabama and neighboring states, allowing patients to participate in research projects, including therapeutic trials.
What do you find makes the science community here unique?
I found the science community welcoming, and I was pleasantly surprised to see how collaborations across departments and even schools were encouraged and facilitated. This makes UAB a wonderful scientific community.