Sefaxersen Phase 2 Trial Signals Proteinuria Reduction in IgA Nephropathy
Key Takeaways
- In IgA nephropathy, sefaxersen treatment was associated with lower proteinuria at week 29, while kidney function remained stable.
- Selective reductions were observed in alternative pathway-related biomarkers, while classical pathway activity did not change.
Sefaxersen is an antisense oligonucleotide targeting complement factor B, studied in patients with biopsy-confirmed disease. Kidney function remained stable through the main assessment as proteinuria declined.
The study enrolled 23 patients in this global exploratory trial. Eligibility required biopsy-confirmed IgA nephropathy with kidney C3 deposits, hematuria, and 24-hour proteinuria above 1.5 g/day despite maximum tolerated renin-angiotensin-aldosterone-system blockade.
Participants received sefaxersen 70 mg by monthly subcutaneous injection for 24 weeks, followed by a voluntary treatment extension. The prespecified primary endpoint was change in 24-hour urinary protein excretion at week 29 versus baseline.
Baseline geometric mean proteinuria was 2.5 g/day and declined to 1.4 g/day at week 29. Similar reductions were reported for the urinary protein-creatinine ratio and urinary albumin-creatinine ratio. Mean eGFR was 70.4 mL/min/1.73 m2 at baseline and 73.2 mL/min/1.73 m2 at week 29.
Selective reductions were also observed in plasma complement FB and Bb, urinary factor Ba, and serum complement alternative pathway activity, while classical pathway activity was unchanged.
Proteinuria reduction was sustained in all seven participants who entered the voluntary extension, including four who received treatment for more than 12 months.
One treatment-emergent serious adverse event was reported and was not considered related to study drug. Transient, reversible alanine aminotransferase elevations of 3-5 times the upper limit of normal occurred in three individuals without bilirubin change, and those participants remained on study and completed treatment.