Elebsiran is a small interfering RNA (siRNA) that targets hepatitis B virus messenger RNA to reduce hepatitis B surface antigen (HBsAg) production.
It works by silencing HBV gene expression at the post-transcriptional level, thereby decreasing the amount of HBsAg produced by infected hepatocytes.
The siRNA is administered subcutaneously, typically at doses of 100 mg or 200 mg every 4 weeks.
When combined with tobevibart, elebsiran provides a complementary mechanism of action—while tobevibart neutralizes circulating HBsAg and activates immune responses, elebsiran reduces new HBsAg production at the source.
In clinical trials for chronic hepatitis B, elebsiran combined with pegylated interferon alfa achieved HBsAg loss rates of 21-33% at 24 weeks post-treatment, compared to only 5.6% with interferon monotherapy.
The combination therapy was generally safe and well tolerated, with most adverse events being mild to moderate in severity.
One important safety consideration is that elebsiran monotherapy has been associated with ALT flares in some patients with hepatitis D, which led to deferral of further exploration of elebsiran monotherapy in this population.
However, when tobevibart and elebsiran were started simultaneously, no ALT flares were observed, suggesting that tobevibart may ameliorate this risk.