Key Takeaways:
Roche and Ionis said sefaxersen cut proteinuria versus placebo at 37 weeks in the Phase 3 IMAgINATION study, a statistically significant and clinically meaningful result that moves the antisense drug toward regulatory filing in primary IgA nephropathy.
The trial met its primary endpoint on change from baseline in 24-hour urine protein-to-creatinine ratio (UPCR), the companies said on Sept. 23. Sefaxersen is a once-monthly subcutaneous injection designed for self-administration. The safety and tolerability profile matched earlier studies, with no new safety signals identified.
"These interim Phase 3 results show the clinical potential of sefaxersen to modify a key surrogate endpoint of kidney function in people with IgA nephropathy," Levi Garraway, Roche's chief medical officer and head of Global Product Development, said. "Sefaxersen may therefore offer a new treatment option to help slow disease progression and potentially reduce the long-term need for dialysis or kidney transplantation."
IMAgINATION enrolled 459 adults with primary IgAN at high risk of progression, randomized 1:1 to sefaxersen or placebo for 105 weeks. The study stays blinded to measure change in estimated glomerular filtration rate (eGFR) at week 105 — two years of kidney function data that neither company has disclosed. Roche said interim results will go to health authorities and be presented at an upcoming medical congress.
Sefaxersen is a liver-directed antisense oligonucleotide that suppresses production of complement factor B, the first RNA-targeted therapy aimed at IgAN. Serum factor B levels run elevated in IgAN patients; lowering them reduces protein in urine, a marker tied to preservation of long-term kidney function. Roche licensed the drug from Ionis for complement-mediated diseases, paying an upfront fee, a license fee and development milestones, with regulatory and sales milestones plus tiered royalties still ahead.
The readout lands in a crowded field. IgAN affects at least 25 adults per million worldwide each year and is typically diagnosed before age 40, with up to 50% of patients reaching end-stage kidney disease within 20 years of diagnosis, according to Roche. Updated KDIGO 2025 guidelines call for treating both the immune drivers of the disease and the downstream kidney damage, a standard that has pulled several late-stage assets into the same patient population.
Proteinuria reduction is the surrogate regulators have accepted before, but it is not the endpoint that settles durability. The blinded eGFR read at week 105 is the number that will decide whether sefaxersen supports a full approval and how it stacks up against rivals already on the market.
For Ionis, the interim result converts a Phase 3 asset into a near-term milestone stream: regulatory and sales payments under the Roche agreement now sit closer to triggering, on top of tiered royalties on net sales. Roche carries the commercialization cost and the field force, which limits Ionis's downside but also caps its share of the eventual revenue.
Investors get the next hard data point when Roche presents the interim analysis at a medical congress and files with health authorities. The week-105 eGFR result, still blinded, is the swing factor for both the label and the peak-sales math.
This article is for informational purposes only and does not constitute investment advice.
