Sefaxersen


Sefaxersen is an investigational antisense oligonucleotide drug developed by Roche Holding AG in partnership with Ionis Pharmaceuticals. It targets complement factor B to treat complement system-mediated diseases, primarily IgA nephropathy and geographic atrophy secondary to age-related macular degeneration. By inhibiting CFB expression, Sefaxersen reduces harmful inflammation driven by the alternative complement pathway.
As of 2025, it is in Phase 2/3 trials for IgAN and Phase 2 trials for GA.

Mechanism of action

Sefaxersen is an antisense oligonucleotide that binds to the messenger RNA of the complement factor B gene, preventing CFB protein production. CFB is a key component of the alternative pathway of complement activation, which can drive inflammation and tissue damage in diseases like IgAN and GA. By reducing CFB levels, Sefaxersen dampens this pathway, aiming to slow disease progression. This RNA-targeted approach offers precision compared to traditional drugs, making it suitable for complex conditions.

Development

Sefaxersen was developed by Ionis Pharmaceuticals, a pioneer in RNA-targeted therapeutics, in partnership with Roche for late-stage clinical development and potential commercialization. Ionis’ expertise in antisense technology complements Roche’s focus on neurology, rare diseases, and ophthalmology. Early clinical trials demonstrated that Sefaxersen effectively reduced complement factor B levels, supporting its advancement into Phase 2/3 trials for IgA nephropathy and Phase 2 trials for geographic atrophy.
Sefaxersen is currently being evaluated in clinical trials for its safety and efficacy in treating the following complement-mediated diseases.

IgA Nephropathy (IgAN)

Sefaxersen is in Phase 2/3 trials for primary IgA nephropathy, a kidney disorder characterized by the deposition of IgA immune complexes in the glomeruli, leading to inflammation and progressive kidney damage. Results from Phase 2 trials showed a significant reduction in proteinuria and stabilization of kidney function in treated patients, supporting the continuation of development. The ongoing Phase 3 trial is focused on evaluating efficacy, safety, and pharmacokinetics in patients at high risk of disease progression.

Geographic Atrophy (GA)

Overactivation of the alternative complement pathway plays a key role in the progression of GA. In Phase 1 studies involving healthy volunteers, Sefaxersen was shown to reduce systemic CFB levels and overall complement activity, supporting its potential use in GA treatment. Sefaxersen entered Phase 2 trials for geographic atrophy, an advanced form of age-related macular degeneration that leads to irreversible vision loss. However, further development of Sefaxersen for GA has been discontinued by Ionis Pharmaceuticals.