Elebsiran Plus Tobevibart Suppresses HDV RNA in Phase 3 ECLIPSE 1 Trial

Monthly subcutaneous elebsiran plus tobevibart met the primary endpoint of the phase 3 ECLIPSE 1 trial in adults with chronic hepatitis delta (CHD), with 44% of patients achieving undetectable hepatitis D virus (HDV) RNA plus alanine aminotransferase (ALT) normalization at week 48 compared with 0% of patients in a delayed treatment group at week 12 (P < .0001).¹,²

Nancy Reau, MD, of Rush University Medical Center, presented the topline results in a late-breaking oral session at The Liver Meeting 2026 in Denver, Colorado.¹,²

“For people living with CHD, the goal is not simply to reduce the amount of virus, but to drive it to levels where it is no longer detectable since ongoing HDV replication drives liver disease progression,” Reau said in a statement.²

HDV infects only people with hepatitis B virus (HBV) and affects nearly 5% of people with chronic hepatitis B, an estimated 12 million people worldwide, according to the World Health Organization. It is considered the most severe form of chronic viral hepatitis, and HDV superinfection accelerates progression to more severe liver disease in 70% to 90% of cases.³ In June 2025, the International Agency for Research on Cancer classified HDV as carcinogenic to humans (Group 1), citing sufficient evidence that it causes hepatocellular carcinoma.⁴

Treatment options remain limited. In May 2026, the US Food and Drug Administration (FDA) granted accelerated approval to bulevirtide (Hepcludex), a once-daily subcutaneous entry inhibitor, as the first US treatment for chronic HDV infection, following a 2022 complete response letter. In the pivotal MYR301 trial, 20% of patients receiving bulevirtide achieved undetectable HDV RNA at week 48.⁵

How Do Elebsiran and Tobevibart Work?

The investigational regimen is given as 2 sequential subcutaneous injections every 4 weeks. Elebsiran, an HBV-targeting small interfering RNA (siRNA), is designed to limit production of hepatitis B surface antigen (HBsAg), which HDV requires to replicate. Tobevibart, a broadly neutralizing monoclonal antibody targeting HBsAg, is designed to block viral entry into hepatocytes and clear circulating viral particles.²

In the phase 2 SOLSTICE trial, 66% of patients receiving the combination achieved undetectable HDV RNA at week 48 and 91% achieved HBsAg below 10 IU/mL.⁶ Undetectable HDV RNA reached 88% by week 96, including in patients with compensated cirrhosis.¹ The regimen has received FDA breakthrough therapy and fast track designations.²

What Did ECLIPSE 1 Show?

ECLIPSE 1 (NCT06903338) enrolled adults without cirrhosis or with compensated cirrhosis (Child-Pugh-Turcotte score <7) who had HDV RNA of at least 500 IU/mL and elevated ALT (<5 × the upper limit of normal) while receiving nucleos(t)ide analog therapy. Patients who received HDV antivirals within 24 weeks were excluded.¹

A total of 124 patients at 39 sites in 10 countries were randomly assigned 2:1 to immediate treatment with elebsiran 200 mg plus tobevibart 300 mg every 4 weeks (n = 83) or delayed treatment beginning at week 12 (n = 41). Approximately 55% of patients had compensated cirrhosis. Mean baseline HDV RNA was 5.5 log₁₀ IU/mL, and mean ALT was 100.1 U/L.¹,² All patients in the immediate treatment arm completed 48 weeks of therapy.²

Results at week 48 for the treatment arm vs week 12 for the delayed treatment arm were:²

• Undetectable HDV RNA (target not detected) plus ALT normalization (primary endpoint): 44% vs 0% (P < .0001)
• Undetectable HDV RNA (key secondary endpoint): 79% vs 0% (P < .0001)
• Virologic response (undetectable HDV RNA or a reduction of at least 2 log₁₀): 100% vs 0%
• ALT normalization: 53% vs 5%
• HBsAg below 10 IU/mL (exploratory): 95% vs 0%

Undetectable HDV RNA was achieved in 85% of patients with cirrhosis (n = 46) and 73% of those without cirrhosis (n = 37).²

What Safety Findings Were Reported?

Most treatment-related adverse events (TRAEs) were mild to moderate and transient. The most common was influenza-like symptoms, which occurred mainly with the first dose and mostly resolved within 48 hours. One grade 3 TRAE, a decreased neutrophil count, resolved within 15 days, and there were no treatment interruptions or discontinuations.²

What Comes Next for Elebsiran and Tobevibart?

The results are sponsor-reported topline data. ECLIPSE 1 was open label, and its primary comparison pits 48 weeks of treatment against 12 weeks without treatment rather than an active comparator. Cross-trial comparisons with bulevirtide should be made cautiously.

ECLIPSE 2 (NCT07128550) is evaluating a switch to elebsiran and tobevibart in patients who have not achieved viral suppression with bulevirtide, and ECLIPSE 3 (NCT07142811) is comparing the regimen head-to-head with bulevirtide in bulevirtide-naive patients. Data from both are expected in the first quarter of 2027, with an FDA filing planned for mid-2027.²

References:

1. Reau N, Chow S, Jucov A, et al. Primary endpoint results of ECLIPSE 1: a randomized open-label phase 3 study evaluating efficacy and safety of elebsiran and tobevibart for chronic hepatitis delta. Late-breaking abstract presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Vir Biotechnology. Vir Biotechnology announces primary endpoint met in pivotal phase 3 ECLIPSE 1 trial for elebsiran and tobevibart in chronic hepatitis delta. News release. Published November 8, 2026. Accessed November 8, 2026. https://investors.vir.bio/news/news-details/2026/Vir-Biotechnology-Announces-Primary-Endpoint-Met-in-Pivotal-Phase-3-ECLIPSE-1-Trial-for-Elebsiran-and-Tobevibart-in-Chronic-Hepatitis-Delta/default.aspx
3. World Health Organization. Hepatitis D. Fact sheet. Updated July 25, 2025. Accessed November 8, 2026. https://www.who.int/news-room/fact-sheets/detail/hepatitis-d
4. Karagas MR, Kaldor J, Michaelis M, et al. Carcinogenicity of hepatitis D virus, human cytomegalovirus, and Merkel cell polyomavirus. Lancet Oncol. Published online June 27, 2025. doi:10.1016/S1470-2045(25)00403-6
5. Myshko D. FDA approves first treatment for chronic hepatitis delta virus. Managed Healthcare Executive. Published May 22, 2026. Accessed November 8, 2026. https://www.managedhealthcareexecutive.com/view/fda-approves-first-treatment-for-chronic-hepatitis-delta-virus
6. Asselah T, Chattergoon MA, Jucov A, et al. A phase 2 trial of tobevibart plus elebsiran in hepatitis D. N Engl J Med. 2026;394(4):343-353. doi:10.1056/NEJMoa2508827