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 lower proteinuria with povetacicept, ravulizumab and sefaxersen than with placebo. The results are based on surrogate measures; longer-term eGFR data are still needed to assess effects on kidney-function decline.
Interim analyses of three phase III trials found that povetacicept, ravulizumab and sefaxersen reduced proteinuria more than placebo in people with IgA nephropathy, according to results presented at the American Society of Nephrology Kidney Week meeting. The findings support activity on a commonly used disease measure, but the trials have not yet reported the longer-term eGFR data needed to assess whether treatment slows loss of kidney function.
In the RAINIER trial, povetacicept lowered geometric mean 24-hour urinary protein-to-creatinine ratio (UPCR) by 52.0% from baseline at week 36, compared with a 4.3% reduction with placebo. The adjusted difference between groups was 49.8 percentage points (95% CI 39.2 to 58.6 in magnitude; P<0.001), according to the published analysis. The interim efficacy population included the first 199 randomized participants from a larger trial of 557 adults.
In I CAN, ravulizumab reduced geometric mean 24-hour UPCR by 46.6% at week 34, compared with 5.6% with placebo. The adjusted geometric mean UPCR was 43.4% lower with ravulizumab than placebo (99% CI 30.1% to 54.2%; P<0.001). The primary analysis covered 352 participants who had reached, or would have reached, week 34. The FDA recently granted ravulizumab accelerated approval to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid progression.
In IMAgINATION, sefaxersen reduced 24-hour UPCR by 46.9% at week 37, compared with a 6.6% reduction with placebo. The relative reduction versus placebo was 43.1% (95% CI 32.5% to 52.0%; P<0.0001). The supplied trial summary identifies 408 people in its primary cohort, randomized equally between treatment and placebo. The source material does not provide further details about sefaxersen’s mechanism, safety results or other trial outcomes.
Proteinuria Results Need Kidney-Function Follow-Up
Proteinuria—protein in urine—is used as a surrogate measure in IgA nephropathy trials because it can help indicate disease activity and treatment response. The reported differences from placebo provide evidence that all three treatments affect this measure over the periods studied. They do not, by themselves, establish how much a drug will preserve kidney function over time or whether patients will avoid kidney failure.
That distinction matters for patients and clinicians weighing potential benefits against treatment burden and risk. Povetacicept is given by subcutaneous injection every four weeks in RAINIER; ravulizumab is given intravenously every eight weeks in I CAN. The trials used different designs, treatment periods and analysis populations, so their percentages should not be treated as a direct comparison of the drugs. Longer follow-up, including eGFR outcomes, will be needed to clarify clinical benefit.
Products Worth Considering
eufy Security Essential Alarm System, 7-Piece, No Monthly Fee
Google Nest Learning Thermostat (4th Gen) with Nest Temperature Sensor (2nd Gen), Obsidian
Shark Navigator Robot Vacuum with 30-Day Self-Emptying Base, White (AV2110S)
As an affiliate, we earn on qualifying purchases.
Three Trials, Different Treatment Targets
The studies tested distinct approaches in adults with biopsy-confirmed IgA nephropathy receiving standard or supportive care. Povetacicept is an investigational TACI fusion protein designed to inhibit BAFF and APRIL, signaling molecules involved in B-cell activity. Ravulizumab inhibits terminal complement protein C5. The supplied report describes sefaxersen’s trial results but does not include enough information to specify its mechanism.
The RAINIER interim cohort was drawn from an ongoing study with 557 participants in the main cohort; 97% were taking renin-angiotensin system inhibitors and 66% SGLT2 inhibitors. Its primary endpoint is total eGFR slope at week 104. I CAN randomized 485 adults with persistent proteinuria despite standard care, with the interim efficacy analysis covering 352 participants. Both studies are continuing follow-up. The source says complete two-year data will assess eGFR slope for ravulizumab; continued approval may depend on evidence that it slows kidney-function decline.
“Povetacicept is an investigational TACI fusion protein designed to inhibit both BAFF and APRIL, two cytokines involved in B-cell activation, differentiation, and survival.”
— Richard Lafayette, MD, speaking to MedPage Today
Long-Term Kidney Outcomes Are Pending
The interim results report changes in UPCR, not final evidence that the drugs slow eGFR decline or prevent kidney failure. The studies remain underway, and the key longer-term kidney-function analyses have not yet been reported. The available source also does not provide complete trial details for sefaxersen, including its mechanism and safety findings.
Safety information varies in the supplied account. In RAINIER’s overall safety population, adverse events occurred in 75% of povetacicept recipients and 78% of placebo recipients; 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 I CAN, adverse events were reported in 69.5% with ravulizumab and 75.8% with placebo, while serious events occurred in 4.6% and 9.0%; no meningococcal infections or treatment-related deaths were reported. These figures do not settle longer-term safety questions, and no comparable sefaxersen safety data were included in the source material.
Week 104 Results Will Test Durability
RAINIER is continuing toward its primary week-104 endpoint, total eGFR slope. The FDA is reviewing povetacicept for accelerated approval, with a target action date of November 30, according to the report. That date is a target, not confirmation of an agency decision. The next major evidence will include whether the interim proteinuria effect is sustained and how kidney function changes over longer follow-up.
I CAN is also expected to provide two-year data on annualized eGFR slope, which will help test whether ravulizumab’s proteinuria reduction corresponds to slower kidney-function loss. The supplied material does not give a specific date for those results or a timeline for additional IMAgINATION findings. Until those data are available, the three interim analyses should be read as evidence of changes in a surrogate measure rather than a final account of long-term clinical benefit.
Key Questions
What did the three interim analyses find?
Each trial reported a greater reduction in 24-hour UPCR with active treatment than with placebo: povetacicept at week 36, ravulizumab at week 34 and sefaxersen at week 37.
Do these results show that the drugs prevent kidney failure?
No. The reported findings concern proteinuria, a surrogate measure. Longer-term eGFR results are still needed to determine whether treatment slows kidney-function decline.
Which of the drugs has FDA accelerated approval?
Ravulizumab recently received FDA accelerated approval to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid progression. The report says povetacicept is under FDA review; it does not report an approval decision.
When will longer-term results be available?
RAINIER is continuing toward its week-104 eGFR endpoint, and I CAN is expected to report two-year eGFR-slope data. The source material does not specify dates for those results or for further IMAgINATION findings.
Source: rss
