The FDA has granted accelerated approval to atrasentan (Vanrafia; Novartis), a once-daily, non-steroidal, selective endothelin A (ETA) receptor agonist, for use in reducing proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk of rapid disease progression, according to a news release from Novartis.1
Immunoglobulin A nephropathy can damage the kidneys over time. | Image Credit: © yuwaree (Generated with AI) - stock.adobe.com
Atrasentan, an oral treatment, offers patients and treatment providers more options for treatment given its ease of administration and the ability to add the treatment to supportive care. This includes care with a renin-angiotensin system (RAS) inhibitor with or without a sodium-glucose co-transporter-2 (SGLT2) inhibitor.1
In the phase 3 ALIGN multinational, double-blind, randomized, controlled clinical trial (NCT04573478), atrasentan was evaluated in adults with biopsy-proven IgA nephropathy. Patients were required to have a total urinary protein excretion of at least 1 g per day and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area, both indicators of proteinuria, according to the study authors. Patients were randomized to be administered either atrasentan 0.75 mg per day or a matched placebo for 132 weeks.2,3
According to a prespecified interim analysis conducted at 36 weeks, among the first 270 patients in the main trial stratum, the geometric mean percentage change in the urinary protein-to-creatinine ratio relative to baseline was higher with atrasentan (−38.1%) than with placebo (−3.1%), with a geometric mean between-group difference of −36.1 percentage points (95% CI, −44.6 to −26.4; P < .001), achieving the primary trial end point.2
Critically, in ALIGN, the percentage of patients with adverse events (AEs) did not substantially differ between the atrasentan and placebo groups. Accordingly, there were no apparent cases of cardiac failure or severe edema observed across the cohort. The investigators concluded that atrasentan resulted in a meaningful and clinically significant reduction in proteinuria in this patient population, boosting the treatment towards accelerated approval.2
"Today's approval marks an important milestone for people living with IgA nephropathy, offering a new option that can be seamlessly integrated into their existing treatment plan, with no REMS requirement," Richard Lafayette, MD, FACP, study investigator on the ALIGN clinical trial, said in the news release. “Taking early, decisive action is critical to help improve outcomes for these patients who too often progress toward kidney failure."1
According to Novartis, almost 13 out of every million individuals in the US are diagnosed with IgAN, making it one of the most diagnosed autoimmune kidney diseases. The disease is progressive and rare, attacking the kidneys using a patient’s immune system and inducing glomerular inflammation and proteinuria as a result. Transitioning to kidney failure is a major concern for patients in this population; up to 50% of patients with IgAN with persistent proteinuria will progress to kidney failure within 10 to 20 years of diagnosis. Developing novel treatments that can effectively reduce proteinuria can help improve outcomes for patients with IgAN and help manage their condition without the eventual need for maintenance dialysis or kidney transplantation.1
Accelerated approval for atrasentan will offer pharmacists a new option for patient counseling if proteinuria is suspected or confirmed in those with IgAN. Importantly, though, it remains to be seen whether atrasentan can slow kidney function decline in this patient population. The ALIGN trial is currently ongoing, with data regarding eGFR decline expected in 2026, which could reinforce the positive data surrounding atrasentan as it is considered for traditional FDA approval.1
"The approval of [atrasentan] broadens the treatment landscape and expands the opportunity to tailor care in a disease that can impact each patient so differently,” Bonnie Schneider, director and cofounder of the IgA Nephropathy Foundation, said in the news release.1
REFERENCES
1. Novartis. Novartis receives FDA accelerated approval for Vanrafia (atrasentan), the first and only selective endothelin A receptor antagonist for proteinuria reduction in primary IgA nephropathy (IgAN). News Release. Released April 2, 2025. Accessed April 3, 2025. https://www.novartis.com/us-en/news/media-releases/novartis-receives-fda-accelerated-approval-vanrafia-atrasentan-first-and-only-selective-endothelin-receptor-antagonist-proteinuria-reduction-primary-iga-nephropathy-igan
2. Heerspink HJL, Jardine M, Kohan DE, et al, Atrasentan in patients with IgA nephropathy. N Engl J Med.2025;392(6):544-554. doi:10.1056/NEJMoa2409415
3. ClinicalTrials.gov. Atrasentan in patients with IgA nephropathy (ALIGN). National Library of Medicine. Last Updated October 15, 2024. Accessed April 3, 2025. https://clinicaltrials.gov/study/NCT04573478