Roche's Genentech has put numbers behind its phase 3 success in IgA nephropathy (IgAN), reporting that antisense oligonucleotide sefaxersen reduced a key marker of kidney damage by 43.1% compared with placebo.
In the late-stage trial, called IMAgINATION, patients receiving the drug candidate demonstrated a significant reduction in proteinuria—the presence of excess protein in urine that signals kidney damage—at 37 weeks. Among patients with blood in their urine at baseline, a greater proportion of those receiving sefaxersen experienced resolution of the condition compared with placebo, the company reported. The drug was well tolerated, with no new safety signals and a safety profile consistent with an earlier phase 2 trial.
Roche presented the detailed results at the American Society of Nephrology's Kidney Week meeting in Denver, a month after first announcing that the trial had met its primary endpoint. The company plans to continue the study to measure kidney function over two years while sharing data with regulatory agencies "with the goal of bringing this treatment to patients as soon as possible."
Sefaxersen, designed to be administered through a once-monthly subcutaneous injection, inhibits the production of complement factor B, a protein involved in the immune system's alternative complement pathway. Overactivation of this pathway contributes to kidney damage in patients with IgA nephropathy.
"By inhibiting complement factor B in the liver, sefaxersen may offer a novel approach to slow disease progression in IgAN, potentially helping patients delay or avoid long-term dialysis or kidney transplantation," Genentech Chief Medical Officer and Head of Global Product Development Levi Garraway, M.D., Ph.D., said in the release.
Roche licensed sefaxersen, previously called IONIS-FB-LRx, from Ionis Pharmaceuticals in 2022, building on an option agreement signed in 2018. Expecting the IgAN market to grow rapidly through the end of the decade, Roche has projected peak sales of 1 billion to 2 billion Swiss francs for sefaxersen.
But Roche's drug won't be the only option in town. Novartis gained accelerated FDA approval for its own factor B inhibitor, Fabhalta, in 2024, followed by full approval in July 2026. The twice-daily oral medication could have an advantage over Roche's once-monthly injection when it comes to ease of administration. However, Fabhalta has been associated with increased cholesterol levels, while Roche's drug showed no such effect in a previous phase 2 study.