OTSKY VOYXACT: 2-Year eGFR Stabilization in IgAN

Otsuka (OTSKY) reported positive full Phase 3 VISIONARY results showing VOYXACT (sibeprenlimab-szsi) achieved statistically significant stabilization of kidney function, with evidence of improvement over two years, in adults with immunoglobulin A nephropathy (IgAN). The company called it the first APRIL inhibitor to demonstrate long-term eGFR benefit versus placebo. The detailed 24-month numbers landed at the GlomCon Hawaii 2026 conference on August 3: the annualized eGFR slope was +0.3 mL/min/1.73 m²/year (95% CI, -0.4 to 0.9) with sibeprenlimab versus -4.2 (95% CI, -4.9 to -3.6) with placebo — a +4.5 mL/min/1.73 m²/year treatment difference (p<0.0001). At 24 months the least-squares mean change from baseline was +1.3 mL/min/1.73 m² versus -7.9 for placebo, a +9.2 mL/min/1.73 m² difference (p<0.0001). The drug held kidney decline to roughly the physiologic rate of aging.

OTSKY, the ADR for Otsuka Holdings, closed at $34.41 on light volume of roughly 51,000 shares. The ADR trades over the counter, so market cap data is not available through standard US data providers. Otsuka Holdings is primarily listed on the Tokyo Stock Exchange.

The VISIONARY data

VISIONARY (NCT05248646) is a global, double-blind, placebo-controlled Phase 3 trial enrolling 510 patients (259 sibeprenlimab, 251 placebo). The primary endpoint, met at 9 months, showed a 50.2% reduction in 24-hour urine protein-to-creatinine ratio versus a 2.1% increase on placebo (p<0.001). That proteinuria result was the basis for the FDA’s accelerated approval on November 25, 2025.

The 12-month interim eGFR analysis, presented at the ERA Congress in June, showed a treatment effect of +5.5 mL/min/1.73 m², with sibeprenlimab gaining 0.7 while placebo declined 4.8. The full 24-month readout, announced July 2, confirmed the trend: statistically significant stabilization on both annualized eGFR slope and mean change from baseline. Otsuka did not release the specific 24-month slope number in the topline announcement, saving it for the GlomCon presentation.

Biomarker data at week 48 showed APRIL reduced 95.8% and galactose-deficient IgA1 reduced 67.1%. Safety was comparable to placebo, with infections at 49% versus 45%.

Why eGFR matters

Proteinuria reduction is a surrogate endpoint. eGFR slope is the endpoint that shows whether a drug actually preserves kidney function over time. The FDA granted accelerated approval to VOYXACT on the proteinuria surrogate; the 24-month eGFR data is what Otsuka needs to convert that to traditional approval via a rolling sBLA submission. The KDIGO 2025 IgAN guideline targets reducing kidney function decline to near-physiological levels, under 1 mL/min/1.73 m² per year.

For more on how surrogate endpoints interact with FDA approval pathways, see the guide to accelerated approval.

The IgAN competitive field

The IgAN market now has three 2025-2026 entrants with distinct mechanisms. Otsuka’s VOYXACT selectively blocks APRIL, reducing pathogenic Gd-IgA1 production without broad B-cell depletion. Vera Therapeutics’ Trutakna (atacicept), approved July 7, 2026, blocks both BAFF and APRIL. Novartis’ Fabhalta (iptacopan), approved July 17, 2026, inhibits complement factor B.

The regulatory gap is the story. Fabhalta holds traditional approval. VOYXACT and Trutakna hold accelerated approvals, both requiring confirmatory eGFR data. If VOYXACT’s 24-month numbers confirm the topline claim, Otsuka closes that gap. Vertex’s povetacicept, another BAFF/APRIL inhibitor, has a PDUFA date of November 30, 2026, adding a fourth mechanism-adjacent entrant.

What to watch next

The GlomCon presentation on August 3 delivered the specific 24-month eGFR slope number — an annualized +0.3 mL/min/1.73 m²/year for sibeprenlimab versus -4.2 for placebo (p<0.0001), with a +9.2 mL/min/1.73 m² 24-month mean change difference. The slope effectively halted kidney decline, and the mean-change figure even shows slight improvement, strengthening the case for converting VOYXACT’s accelerated approval to traditional approval via the rolling sBLA. The next catalyst is Otsuka’s completion of the sBLA and the FDA’s review.

Source: Otsuka press release | VISIONARY on ClinicalTrials.gov