What ECLIPSE 1 Means for Hepatitis Delta Treatment, With Nancy Reau, MD

Monthly subcutaneous elebsiran plus tobevibart achieved undetectable hepatitis D virus (HDV) RNA with alanine aminotransferase (ALT) normalization in 44% of adults with chronic hepatitis delta at Week 48, compared with 0% in a delayed-treatment arm, according to results from the phase 3 ECLIPSE 1 trial presented at AASLD The Liver Meeting 2026.¹,² ECLIPSE 1 is the first pivotal trial from the ECLIPSE registrational program to report.¹

Nancy Reau, MD, of Rush University Medical Center, presented the findings and discussed them in an interview with HCPLive. She emphasized HDV remains underdiagnosed, as identifying it depends first on diagnosing hepatitis B virus infection, which often goes unrecognized in the US.

“In order to find Delta, you first have to find B,” Reau said.

How Did Elebsiran and Tobevibart Perform in ECLIPSE 1?

The combination pairs elebsiran, a small interfering RNA targeting hepatitis B surface antigen (HBsAg) production, with tobevibart, a monoclonal antibody designed to bind viral particles and block entry. ECLIPSE 1 randomized 124 adults on nucleos(t)ide analog therapy, approximately 55% with compensated cirrhosis, 2:1 to elebsiran 200 mg plus tobevibart 300 mg every 4 weeks (n = 83) or treatment delayed until Week 12 (n = 41).¹,² Mean baseline HDV RNA was 5.5 log10 IU/mL.¹

The primary endpoint of HDV RNA target not detected plus ALT normalization was met by 44% of participants at Week 48 vs 0% in the delayed arm (P < .0001).² HDV RNA target not detected occurred in 79% vs 0% (P < .0001), and ALT normalization occurred in 53% vs 5%. HBsAg fell below 10 IU/mL in 95% of treated participants.²

Reau noted all participants achieved virologic response by Week 24, and HDV RNA target not detected rates were still climbing at Week 48. Among patients with compensated cirrhosis, 85% achieved target not detected, compared with 73% without cirrhosis.²

What Does ECLIPSE 1 Mean for HDV Care?

“You cannot blow a horn about efficacy without talking about safety,” Reau said.

All participants completed 48 weeks of treatment, with no treatment interruptions or discontinuations.² One grade 3 treatment-related adverse event, a decrease in neutrophil count, resolved within 15 days, and the most common treatment-related adverse event was flu-like symptoms, mainly after the first dose.² Reau noted 1 episode of neutropenia also occurred during the delayed-treatment period.

Reau said the once-monthly regimen of 2 subcutaneous injections offers convenience, whether administered at home or in clinic. She also highlighted new AASLD guidance announced at the meeting, a companion to the hepatitis B guidance, advocating screening for HDV in every person with hepatitis B, ideally through reflex testing.

Bulevirtide (Hepcludex) received accelerated approval from the US Food and Drug Administration in May 2026 as the first therapy for chronic HDV.³ ECLIPSE 2 is evaluating a switch to elebsiran plus tobevibart in patients without viral suppression on bulevirtide, and ECLIPSE 3 is a head-to-head comparison with bulevirtide, with data expected in the first quarter of 2027. Vir Biotechnology plans a US regulatory submission in mid-2027; the regimen holds FDA Breakthrough Therapy and Fast Track designations.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. 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. Published November 8, 2026. Accessed November 13, 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. Bulevirtide receives historic first FDA approval for chronic hepatitis delta. HCPLive. Published May 22, 2026. Accessed November 13, 2026. https://www.hcplive.com/view/bulevirtide-historic-first-fda-approval-chronic-hepatitis-delta