TL;DR
Turn quiet afternoons into listening time
- Thousands of audiobooks, podcasts and originals
- Listen on your phone, tablet or Echo — also offline
- Cancel anytime
Interim phase III analyses presented at the American Society of Nephrology Kidney Week meeting found that povetacicept, ravulizumab and sefaxersen each reduced proteinuria compared with placebo in people with IgA nephropathy. The studies have not yet established whether those reductions translate into slower long-term loss of kidney function; eGFR follow-up is continuing.
Interim phase III analyses of three treatments for IgA nephropathy found significantly greater reductions in proteinuria than placebo, according to results presented at the American Society of Nephrology Kidney Week meeting. The findings cover investigational povetacicept and sefaxersen, as well as ravulizumab, which has received FDA accelerated approval for reducing proteinuria in adults with primary IgA nephropathy; none of these interim results establishes whether treatment slows long-term kidney-function decline.
In the RAINIER trial, the geometric mean 24-hour urinary protein-to-creatinine ratio (UPCR) fell 52.0% by week 36 among patients given povetacicept, compared with 4.3% with placebo. The adjusted difference was 49.8 percentage points (95% CI 39.2 to 58.6 in magnitude; P<0.001). The prespecified interim efficacy analysis covered the first 199 randomized patients. In the overall safety population of 557, adverse events were reported in 75% of the povetacicept group and 78% of the placebo group; serious adverse events occurred in 3% and 4%, respectively. Injection-site reactions were reported in 15% versus 2%, nearly all mild, and no deaths occurred.
In the I CAN trial, ravulizumab reduced geometric mean 24-hour UPCR by 46.6% at week 34, compared with 5.6% with placebo. The adjusted relative difference was 43.4% (99% CI 30.1% to 54.2%; P<0.001). The primary analysis included 352 of the trial’s 485 participants who had reached or would have reached week 34. In the IMAgINATION trial, sefaxersen reduced 24-hour UPCR by 46.9% at week 37, versus 6.6% with placebo, a relative difference of 43.1% (95% CI 32.5% to 52.0%; P<0.0001).
Additional reported measures included reductions in hematuria and changes in disease-related biomarkers. In RAINIER, 42% of patients receiving povetacicept reached a UPCR below 0.5 g/g, compared with 6% on placebo; hematuria resolved in 85% and 23%, respectively. I CAN researchers also reported better hematuria outcomes and reductions in several urinary biomarkers with ravulizumab. These measures supplement the proteinuria results but do not replace the longer-term kidney-function outcomes still being studied.
Proteinuria Results Need Long-Term Follow-Up
Proteinuria is a marker of kidney damage and a commonly used surrogate endpoint in IgA nephropathy research. The similar direction of results across three separate trials gives clinicians and patients evidence that each treatment reduced this marker over the measured period. However, the findings do not show that the drugs have the same mechanism, safety profile, practical use or effect on disease progression.
The distinction matters because the main question for patients is whether treatment can preserve kidney function over time, not only lower protein in urine at an interim visit. The trials are continuing to assess eGFR, a measure of how well the kidneys filter blood. Those data will help determine whether the observed reductions are accompanied by sustained clinical benefit.
Products Worth Considering
OMRON Complete 2-in-1 Upper Arm Blood Pressure Monitor with EKG
Levoit Eleva 300X HEPA Air Purifier for Home and Bedroom
Bowflex PR1000 Home Gym
As an affiliate, we earn on qualifying purchases.
Three Trials, Different Treatment Approaches
The studies evaluated adults with biopsy-confirmed IgA nephropathy who had persistent disease or proteinuria despite standard supportive care. RAINIER tested povetacicept, an investigational fusion protein designed to inhibit BAFF and APRIL, signals involved in B-cell activity. Its participants continued background care, including renin-angiotensin system inhibitors for 97% and SGLT2 inhibitors for 66% of the main cohort.
I CAN tested ravulizumab, an intravenous terminal complement C5 inhibitor given every eight weeks. The FDA recently granted it accelerated approval to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid progression. IMAgINATION studied subcutaneous sefaxersen. The supplied trial summary reports its proteinuria result and that 408 participants in the primary cohort were randomized, but does not provide further drug-mechanism or safety details.
All three analyses were presented at the same Kidney Week meeting. Their time points and analysis populations differ, so the percentage reductions should not be read as a direct comparison or ranking of the drugs.
“By targeting both BAFF and APRIL, povetacicept is intended to address upstream drivers of IgAN and reduce the production of pathogenic immune complexes that contribute to kidney injury and eventually kidney failure.”
— Richard Lafayette, MD, speaking to MedPage Today
Kidney Function Outcomes Still Pending
The interim results primarily report proteinuria changes. They do not establish whether any of the three treatments slows eGFR decline, prevents kidney failure or delivers lasting benefit. RAINIER is continuing toward its week-104 primary endpoint of total eGFR slope. I CAN also requires longer-term follow-up, with complete two-year data intended to assess annualized eGFR slope; continued approval of ravulizumab may depend on confirming slowed decline in kidney function.
The supplied report does not give detailed IMAgINATION safety findings or further follow-up plans. It also does not provide head-to-head comparisons: each drug was tested in a separate trial, with different populations, assessment weeks and analysis groups. The results therefore cannot establish which treatment is more effective or appropriate for an individual patient.
Week-104 and Two-Year Results
Researchers will continue following trial participants for longer-term kidney outcomes. The key pending milestones include RAINIER’s week-104 eGFR-slope endpoint and the planned two-year eGFR data in I CAN. Those results are needed to assess whether the interim proteinuria reductions correspond to sustained preservation of kidney function.
Povetacicept is under FDA review for accelerated approval, with a November 30 target action date reported for the agency’s decision. The interim analysis itself does not establish the outcome of that review. Ravulizumab already has accelerated approval for reducing proteinuria in the specified adult population, while longer-term evidence remains relevant to confirming clinical benefit. The source material gives no specific regulatory timeline for sefaxersen.
Key Questions
What did the three interim analyses find?
Each reported a greater reduction in urinary protein with the study drug than with placebo: povetacicept at week 36, ravulizumab at week 34 and sefaxersen at week 37. The trials were separate, so their results are not a direct comparison.
Do the results show that the drugs preserve kidney function?
Not yet. The reported interim results concern proteinuria. Longer-term eGFR data are still being collected to assess whether the reductions accompany slower loss of kidney function.
Which drug already has FDA approval?
Ravulizumab recently received FDA accelerated approval to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid progression. Povetacicept is under FDA review, and the supplied report does not state that sefaxersen is approved.
When will more evidence be available?
RAINIER is continuing toward its week-104 eGFR endpoint, and I CAN is expected to report two-year kidney-function data. The source material does not give a release date for those results or a specific timeline for sefaxersen’s next major data update.
Source: rss
