Sefaxersen for immunoglobulin A nephropathy
Fact-checked by 
What is sefaxersen for IgA nephropathy?
Sefaxersen is an experimental injection therapy for immunoglobulin A nephropathy (IgAN), being developed to potentially reduce kidney damage in people with the chronic condition.
In IgAN, excessive protein in urine (proteinuria) and other signs and symptoms of kidney damage are caused by antibody complexes that accumulate in the kidneys, triggering a chain of damaging inflammatory events.
Researchers believe that the immune system’s complement cascade, which normally helps destroy bacteria and other foreign invaders, contributes to this damaging response. A component of the complement system called the alternative pathway appears to play a particularly important role.
Sefaxersen aims to reduce the activity of the alternative complement pathway by targeting a protein, complement factor B, that’s needed to activate it. The medication contains an antisense oligonucleotide — a short strand of genetic material — that binds to the genetic template used to produce complement factor B and triggers its destruction.
This is expected to decrease alternative pathway-related kidney damage in IgAN, while leaving alone other complement pathways important for immune function activity.
Genentech, a subsidiary of Roche, and Ionis are partnering to develop sefaxersen for IgAN. The medication is being tested as a subcutaneous, or under-the-skin, injection.
Therapy snapshot
| Treatment name | Sefaxersen |
| Administration | Subcutaneous injection |
| Clinical testing | Now being tested in a Phase 3 trial |
How will sefaxersen be administered for IgAN?
Clinical trials to date have tested sefaxersen as a subcutaneous injection. In an ongoing Phase 3 trial, the medication is administered every two weeks for the first three doses and every four weeks thereafter. The dose being tested is 70 mg.
Sefaxersen in IgAN clinical trials
Sefaxersen is being tested in the Phase 3 IMAGINATION study (NCT05797610), which launched in 2023. The trial enrolled 459 adults with IgAN who are at risk of disease progression. Participants are receiving sefaxersen or a placebo for as long as two years.
The study’s main goal is to measure the change in urinary protein-to-creatinine ratio (UPCR), an indicator of proteinuria, after 37 weeks, or about 8.5 months. Another key outcome of interest is the change in estimated glomerular filtration rate (eGFR), a measurement of how effectively the kidneys filter blood, over the two-year treatment period.
Interim data announced by the developers in September showed the study met its main goal, with statistically significant and clinically meaningful reductions in proteinuria compared with a placebo.
The launch of IMAGINATION was supported by data from a Phase 2 clinical trial (NCT04014335), which tested sefaxersen in 23 adults with IgAN. Participants were treated for about six months, and some participants entered an extended treatment period. Those results demonstrated that:
- levels of factor B and other components of the alternative pathway decreased during treatment, while markers of non-alternative pathway components remained stable
- about a month after the final dose in the main treatment period, markers of proteinuria had decreased, which was maintained for at least a year in participants who continued treatment
- eGFR stayed relatively stable through week 29
Sefaxersen side effects
In the Phase 2 clinical trial, most safety concerns that emerged during treatment were mild. The most common drug-related reactions were:
- injection site rash
- abnormalities in tests of liver function
More information about the side effects of sefaxersen in people with IgAN will likely be available after the Phase 3 study is completed. The interim data showed that the safety and tolerability profile of sefaxersen was consistent with previously reported information, with no new safety signals identified.
IgA Nephropathy News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
