Roche has reported a phase 3 win for sefaxersen in kidney disease, teeing up talks with regulators about the path to approval for the Ionis Pharmaceuticals-partnered, would-be blockbuster drug candidate.
At a prespecified interim analysis, primary IgA nephropathy (IgAN) patients receiving monthly sefaxersen injections had reduced proteinuria, as measured by 24-hour protein-to-creatinine ratio (UPCR), when compared to placebo. The statistically significant reduction in protein in urine, a marker for kidney health, caused the trial to meet its primary endpoint at the interim Week 37 analysis. Safety and tolerability data were consistent with earlier trials.
The Imagination study will remain blinded to evaluate the change in kidney function at Week 105. But with other research linking reductions in UPCR to the preservation of long-term kidney function, Roche plans to talk to regulators about next steps for the candidate, which was previously called IONIS-FB-LRx.
Week 37 proteinuria data will “hopefully lead to accelerated approval,” Jay Garg, M.D., global head of nephrology, rheumatology and cardiovascular at Roche, said at the Swiss drugmaker’s immunology event in March.
Estimates of sefaxersen’s commercial potential vary. Sefaxersen is “included in most analyst models with sales of 400 million euros ($457 million) forecasted by 2030,” Bruno Eschli, head of investor relations at Roche, said at the March event. Roche is more bullish, putting peak sales at 1 billion to 2 billion euros. The forecasts predate the phase 3 readout.
Roche’s optimism reflects expectations that the IgAN market will grow quickly through 2030 and that its asset can win share. Sefaxersen is an antisense oligonucleotide that inhibits the production of complement factor B, a protein found at high levels in IgAN patients. Inhibiting factor B could stop the complement system from damaging kidney cells.
Novartis’ Fabhalta also inhibits factor B. The FDA granted Fabhalta accelerated approval in IgAN in 2024 and converted the decision into a full authorization this year. Patients take Fabhalta orally twice daily, whereas sefaxersen is administered subcutaneously once monthly. Fabhalta can increase cholesterol, while sefaxersen had no observed effect on cholesterol in its phase 2 data.
Roche paid Ionis $55 million upfront to license sefaxersen in IgAN in 2022. The deal built on a 2018 pact, in which Roche paid $75 million upfront to secure an option on the asset. GSK previously had rights to the program but walked away in 2017.