Within the past three years, four pivotal clinical trials co-led by UAB’s Dana Rizk, M.D., have completely changed the treatment landscape for IgA nephropathy.For decades, being diagnosed with the autoimmune kidney disease IgA (Immunoglobulin A) nephropathy carried a guarded prognosis. Most patients are young adults when they learn they have the disease, and doctors would tell them that there were few good treatment options. Often, patients would try and fail steroid therapy and other immunosuppressors.
“Here you are in the prime of your life, your 20s and 30s, and you are told that you have a chronic progressive disease which means you will likely need dialysis within your lifetime,” said Dana Rizk, M.D., professor in the University of Alabama at Birmingham’s Division of Nephrology and an expert in IgA nephropathy.
But just within the past three years, four pivotal clinical trials, co-led by Rizk, have completely changed the treatment landscape. “I am privileged and lucky to be here and live through this revolution,” Rizk said.
Based on those trial results, three separate treatments, each with a different mechanism of action, have received approval from the U.S. Food and Drug Administration. “It is a wonderful feeling to be able to see a patient in clinic and say, ‘We have several treatment options for you,’” Rizk said. “And if one doesn’t work, we have alternatives.”
IgA nephropathy occurs when the body generates circulating immune complexes that get trapped in the kidney’s filtering units, called glomeruli, leading to inflammation and tissue damage. Symptoms, including blood and protein in the urine, can take years to develop; by the time the disease is recognized, significant damage has often occurred and patients have lost precious filtering function. IgA nephropathy is the most common of a number of rare kidney diseases, affecting around 200,000 people in the United States and millions worldwide.
These new treatments are not cures, but pushing back disease progression can be life-changing, Rizk explains. “Delaying dialysis by 10 or 20 years would have a huge effect on patients and the healthcare system,” she said.
What changed? Research and the National Kidney Initiative partnership
Years of basic research identified the molecular pathways behind IgA nephropathy. Faculty at UAB contributed significantly to these scientific advances through years of collaborations between Jan Novak, Ph.D., in the Department of Microbiology and Bruce Julian, M.D., and Rizk in the Division of Nephrology.
These discoveries gave pharmaceutical companies new targets for developing treatments.
But just as important, Rizk says, was an unprecedented partnership between the FDA and the American Society of Nephrology, known as the Kidney Health Initiative, meant to promote collaboration to advance education and research in nephrology.
Dana Rizk, M.D. “Traditional clinical trials relied on ‘hard endpoints’ as the outcome of a trial: going on dialysis, receiving a kidney transplant or death,” Rizk said. That meant trials took years, enrolling patients was difficult, and pharmaceutical companies had little incentive to risk the investment in experimental therapies that might fail. The Kidney Health Initiative chose IgA nephropathy to test a new trial design and approval pathway in nephrology. “In that framework, reduction in proteinuria — protein in the urine — of a sufficient magnitude would be an acceptable surrogate trial goal,” Rizk said.
The FDA agreed to grant investigational drugs accelerated approval based on this intermediate outcome while expecting the trials to continue and confirm preservation of kidney function. At that point, the investigational drug would be granted full approval.
“That opened the door to a tremendous amount of activity and investment,” Rizk said.
Three major trials, three major successes
Rizk’s years of experience in leading and coordinating trials in rare kidney diseases, along with UAB’s pioneering role in IgA nephropathy research and clinical care, made her a go-to partner for pharmaceutical companies developing innovative drugs. Between 2024 and 2026, Rizk has been a principal investigator and steering committee member for three pivotal Phase 3 trials: APPLAUSE-IgAN, VISIONARY and ORIGIN 3. The work has led to multiple papers in the New England Journal of Medicine co-written by Rizk and accelerated FDA approval for each of these treatments.
- Iptacopan, known as Fabhalta (APPLAUSE-IgAN trial), inhibits the immune system’s alternative complement pathway. It led to significant proteinuria reduction of 38.3 percent and cut kidney function loss per year roughly in half. Fabhalta received accelerated FDA approval in 2024.
- Sibeprenlimab-szsi, known as Voyxact (VISIONARY trial), is the first approved therapy to target APRIL, a protein that interferes with production of IgA by B cells. It reduced proteinuria by about 50 percent, compared with a 2 percent rate for patients receiving placebo. Voyxact received accelerated FDA approval in November 2025.
- Atacicept(ORIGIN 3 trial), known as Trutakna, targets APRIL and BAFF, two proteins that affect a broader population of B cells, and is also expected to reduce the production of IgA. It has also shown significant proteinuria reduction of 45.7 percent from baseline and received accelerated FDA approval in July 2026.
Combined, these results signal not just new therapies but an entirely new era in the treatment for IgA nephropathy. The next steps are to test them in patients earlier in the disease course, and in pediatric patients, who have no good treatment options currently, Rizk says. New trials are also exploring the potential to treat other kidney diseases, and even other autoimmune conditions, with these new drugs.
“As a community in the IgA nephropathy space, we completely upended the clinical trial models, and now people are looking to apply this same model to other rare kidney diseases,” Rizk said. “It tells them we don’t have to have the traditional trials design we have had for the past 20 years.”
Changing people’s lives
These treatments are already making a difference for patients in the Glomerular Disease Clinic that Rizk directs at UAB. “We have changed people’s lives by giving them these therapies,” she said. “I prescribe them in the clinic and have seen the benefits firsthand. Many of the patients who took part in the trials here had tried and failed many other treatments. To know that they now have these new drugs available to them is remarkable.”
Patients with IgA nephropathy come to UAB not only from across Alabama, but from neighboring states as well, Rizk says, and the ability to participate in clinical trials is one major reason they choose to make the trip. “Offering hope for patients is probably the most important thing we do day in and day out,” Rizk said.
Developing a new generation of clinical trialists
Rizk also believes that the successes in IgA nephropathy could inspire more young clinician-scientists to become involved in clinical trials work. “For years, the nephrology space really lagged behind when it came to trials,” Rizk said. “There were huge challenges in recruiting. But these trial successes have opened the door for a whole new world and excitement in the specialty, and hopefully we will engage younger physicians in carrying on this work.”
For more than a decade, in addition to her own trials efforts, Rizk has been leading efforts to encourage younger colleagues to become clinical trialists. In 2025, she was named associate dean for Clinical Trials in the UAB Heersink School of Medicine. And in 2026, she co-led UAB’s new Clinical Trialist Development Program, a key part of the university’s Research Strategic Initiative, along with another renowned physician-trialist, David Kimberlin, M.D.
The goal of the Clinical Trialist Development Program is to increase the number of industry-sponsored clinical trials at UAB — and thereby the number of potential new therapies offered to Alabama patients — by expanding the university’s roster of trialists.
In modern medicine especially, clinician-researchers with expertise in rare conditions or understudied areas are highly sought after by pharmaceutical companies looking for the next IgA nephropathy-style revolution.
“These programs we are creating will foster the next generation of clinical trialists,” Rizk said.