Sefaxersen
An investigational treatment for IgA Nephropathy.
The same compound appears under different names depending on the context. Here is how to identify Sefaxersen wherever you encounter it, plus the key facts at a glance.
- Generic name
- Sefaxersen
- Development codes
- RO7434656, IONIS-FB-LRx
- Drug class
- Antisense oligonucleotide (complement inhibitor)
- Manufacturer
- Roche
- How it's taken
- Sefaxersen is a subcutaneous injection (a shot under the skin) given once a month, designed so patients can give it to themselves.
An investigational antisense therapy for IgA nephropathy that lowers complement Factor B, a liver-made protein that drives the immune reaction linked to kidney damage. It is given as a monthly injection under the skin.
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How Sefaxersen works
Your liver makes a protein called complement Factor B. It is a key part of the alternative complement pathway, a branch of the immune system that is overactive in IgA nephropathy and leads to inflammation and damage in the kidneys' filters[1]. Factor B levels are raised in people with IgAN and are linked to more protein in the urine and worse kidney function[4].
Sefaxersen is an antisense oligonucleotide, a short strand of genetic material built to stick to the messenger RNA (the working copy of a gene) that liver cells use to make Factor B. With that message blocked, the liver makes much less Factor B. A sugar tag called GalNAc steers the drug into liver cells, the main source of Factor B[4]. In Phase 2, alternative pathway activity fell by 39% after 9 weeks, while the classical pathway, a separate branch of the immune defense against infection, stayed unchanged[4].
Mechanism: Antisense oligonucleotide that blocks the messenger RNA the liver uses to make complement Factor B, turning down the alternative complement pathway. A GalNAc sugar tag delivers it to liver cells.
Side effects and safety
Safety data so far come from Phase 1 and Phase 2 studies and the Phase 3 interim analysis. In the Phase 2 study of 23 adults with IgAN, 1 serious adverse event was reported and it was judged unrelated to sefaxersen. A temporary rise in the liver enzyme ALT, to 3 to 5 times the upper limit of normal, occurred in 3 people with no change in bilirubin; the rises reversed, and all 3 stayed in the study and completed treatment[3]. Roche reported that safety in the Phase 3 interim analysis was consistent with earlier data, with no new safety signals, and has not yet published the detailed numbers[1]. Side-effect rates from the 459-person Phase 3 trial will show how common any of these are.
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Sefaxersen
Sefaxersen is a subcutaneous injection (a shot under the skin) given once a month, designed so patients can give it to themselves[1]. In the Phase 3 IMAgINATION trial, participants receive doses on Days 1, 15 and 29 and then once every 4 weeks through Week 105[2]. The Phase 2 study used 70 mg once a month for 24 weeks[3]. The drug stays in the body for weeks, with a half-life of about 5 to 8 weeks in Phase 2 studies, which supports dosing every 4 weeks[4]. Sefaxersen is investigational, meaning no regulator has approved it yet[1].
Clinical trial results
IMAgINATION (NCT05797610) is a randomized, double-blind Phase 3 trial that enrolled 459 adults with primary IgA nephropathy at high risk of progression, assigned 1:1 to sefaxersen or placebo[1][2]. On September 23, 2026, Roche announced that a prespecified interim analysis met the primary endpoint, with sefaxersen lowering urine protein (measured by the 24-hour urine protein-to-creatinine ratio) significantly more than placebo at Week 37. Roche has not released the size of the effect and says the data will be presented at a medical congress and shared with health authorities. The trial stays blinded to measure kidney function (eGFR) at Week 105[1].
The earlier Phase 2 study was single-arm and open-label, meaning all 23 participants received sefaxersen and there was no placebo group. Urine protein fell 43% by Week 29, from a geometric mean of 2.5 to 1.4 grams per day, and average eGFR went from 70.4 to 73.2[3]. Plasma Factor B fell by a mean of 69%, its activated fragment Bb by 79% and urine Factor Ba by 78%[4]. The drop in urine protein held in all 7 participants who joined an optional extension, including 4 treated for more than 12 months[3].
Main registered trial: NCT05797610 on ClinicalTrials.gov. Check it for the current status, sites and contacts before asking about enrollment.
Development history
Roche licensed sefaxersen from Ionis Pharmaceuticals for complement-mediated diseases[1]. It began at Ionis as IONIS-FB-LRx[4]. Roche is developing it under the code RO7434656 and calls it the first mRNA-targeted therapy for IgA nephropathy[1]. It takes a complement-based approach to IgAN, distinct from the APRIL and BAFF pathway drugs also in development.
Explore IgA Nephropathy trials
Other IgA Nephropathy treatments
Common questions about Sefaxersen
▸What is Sefaxersen?
An investigational antisense therapy for IgA nephropathy that lowers complement Factor B, a liver-made protein that drives the immune reaction linked to kidney damage. It is given as a monthly injection under the skin.
▸How does Sefaxersen work?
Your liver makes a protein called complement Factor B. It is a key part of the alternative complement pathway, a branch of the immune system that is overactive in IgA nephropathy and leads to inflammation and damage in the kidneys' filters[1]. Factor B levels are raised in people with IgAN and are linked to more protein in the urine and worse kidney function[4].
Sefaxersen is an antisense oligonucleotide, a short strand of genetic material built to stick to the messenger RNA (the working copy of a gene) that liver cells use to make Factor B. With that message blocked, the liver makes much less Factor B. A sugar tag called GalNAc steers the drug into liver cells, the main source of Factor B[4]. In Phase 2, alternative pathway activity fell by 39% after 9 weeks, while the classical pathway, a separate branch of the immune defense against infection, stayed unchanged[4].
▸What are the side effects of Sefaxersen?
Safety data so far come from Phase 1 and Phase 2 studies and the Phase 3 interim analysis. In the Phase 2 study of 23 adults with IgAN, 1 serious adverse event was reported and it was judged unrelated to sefaxersen. A temporary rise in the liver enzyme ALT, to 3 to 5 times the upper limit of normal, occurred in 3 people with no change in bilirubin; the rises reversed, and all 3 stayed in the study and completed treatment[3]. Roche reported that safety in the Phase 3 interim analysis was consistent with earlier data, with no new safety signals, and has not yet published the detailed numbers[1]. Side-effect rates from the 459-person Phase 3 trial will show how common any of these are.
▸How is Sefaxersen taken?
Sefaxersen is a subcutaneous injection (a shot under the skin) given once a month, designed so patients can give it to themselves[1]. In the Phase 3 IMAgINATION trial, participants receive doses on Days 1, 15 and 29 and then once every 4 weeks through Week 105[2]. The Phase 2 study used 70 mg once a month for 24 weeks[3]. The drug stays in the body for weeks, with a half-life of about 5 to 8 weeks in Phase 2 studies, which supports dosing every 4 weeks[4]. Sefaxersen is investigational, meaning no regulator has approved it yet[1].
▸Is Sefaxersen FDA approved?
Sefaxersen is currently in phase 3 clinical trials for IgA Nephropathy. It has not yet received FDA approval.
▸How does sefaxersen work differently from iptacopan?
Both lower the activity of complement Factor B, in different ways. Sefaxersen blocks the messenger RNA the liver uses to make Factor B, so less of the protein is produced[4]. Iptacopan (Fabhalta) is a capsule that binds the Factor B protein directly and is taken twice a day. Sefaxersen is an injection given once a month[1]. Iptacopan is FDA-approved for IgAN, while sefaxersen is still in Phase 3.
▸How often is sefaxersen administered?
▸What Phase 2 results have been reported?
▸What is the IMAgINATION trial?
IMAgINATION is the Phase 3 trial of sefaxersen in 459 adults with IgA nephropathy at high risk of progression, comparing it with placebo. In September 2026, Roche announced that a planned interim analysis met its primary endpoint, lowering urine protein more than placebo at Week 37. The trial continues to Week 105 to find out whether sefaxersen protects kidney function over the long term[1].
Sources and references
Every factual claim on this page is drawn from the public sources listed below. Click any reference to open the original document.
- Roche · 2026-09-23. Positive interim data shows Roche's sefaxersen significantly reduces proteinuria in people with IgA nephropathy (IgAN). https://www.roche.com/media/releases/med-cor-2026-09-23b
- ClinicalTrials.gov. IMAgINATION: sefaxersen in IgA nephropathy (Phase 3). https://clinicaltrials.gov/study/NCT05797610
- Kidney International 2026;109:592-601 · 2026-03. A single-arm phase 2 trial of an investigational RNA therapeutic to complement factor B sefaxersen for treatment of IgA nephropathy. https://pubmed.ncbi.nlm.nih.gov/41443406/
- Nephrology Dialysis Transplantation 40 (Suppl 3) · 2025-10-21. Suppression of complement alternative pathway by monthly dosing of sefaxersen, a novel antisense oligonucleotide therapy in development for IgAN. https://academic.oup.com/ndt/article/40/Supplement_3/gfaf116.0244/8294637