HDV Combo Shows No Relapses at 2 Years: Tarik Asselah, MD, PhD

Virologic suppression with a once-monthly combination regimen deepened over 2 years of treatment without relapse or treatment failure in patients with chronic hepatitis D virus (HDV) infection, according to 96-week data from the phase 2 SOLSTICE trial¹ (NCT05461170) presented at the 2026 European Association for the Study of the Liver (EASL) Congress, said Tarik Asselah, MD, PhD, professor of hepatology at the Hôpital Beaujon and the University of Paris-Cité, and head of the Viral Hepatitis unit UMR1149 at INSERM, in an interview with The American Journal of Managed Care^® (AJMC^®).

SOLSTICE evaluated tobevibart, a broadly neutralizing anti–hepatitis B virus surface antigen (HBsAg) monoclonal antibody, alone and combined with elebsiran, a small interfering RNA (siRNA) that reduces HBsAg production, in patients with chronic HDV infection.² HDV is the most severe form of chronic viral hepatitis, affecting an estimated 12 million people globally, and requires HBsAg for viral entry and replication.³ It is associated with elevated risks of cirrhosis, hepatocellular carcinoma, and death, with historically limited treatment options.

Asselah discussed why the HBsAg suppression gap between the combination and monotherapy arms widened over time, what the durable target not detected (TND) data mean for off-treatment durability questions that remained open at week 48, and what the 96-week readout confirms that earlier data cuts could only suggest. The findings are being taken forward in the phase 3 ECLIPSE program.

This interview was edited for clarity.

AJMC: The week 48 data showed a clear split between the combination and monotherapy arms on HBsAg suppression with 91% vs 21% of patients achieving suppression levels. What does the week 96 data tell us about whether that separation holds, deepens, or narrows over time?

Asselah: Because of the mechanism of action of these drugs, they are complementary. You have 2 drugs: one is the monoclonal antibody [tobevibart] and one is the siRNA [elebsiran]. At 48 weeks, you are completely right, there's a decrease in HBsAg quantification in the combination and not in the monotherapy, and it persists at 96 weeks. The combination continues to differentiate from the monotherapy, with a much higher proportion of patients achieving HBsAg suppression.

AJMC: One of the outstanding questions from the 48-week data was whether virologic responses would be sustained after treatment ends. Does the 96-week dataset start to answer that, or does it raise new questions about what off-treatment follow-up needs to look like?

Asselah: It's a very important question. The goal of treatment, when you have a viral disease, is to see if there's no more virus—it's TND or no virus detectable by polymerase chain reaction [PCR]. At 48 weeks, that's a high number, and it's increasing at 96 weeks. What is important is that when a patient becomes TND in the blood, it is maintained over time. We have no relapse, no breakthrough, no failure. This is very important, that TND is maintained over time.

AJMC: What would you say the SOLSTICE 96-week data definitively establishes that earlier readouts could not?

Asselah: The early readout is a phase 2 [study] with a small sample size. The first message was very high antiviral efficacy: we can have a high number of patients with undetectable RNA and also a good safety profile. All of this has to be confirmed in phase 3, and there is the ongoing phase 3 ECLIPSE program running currently.

AJMC: You led SOLSTICE and now the ongoing phase 3 ECLIPSE trial. What is the one thing the phase 2 data couldn't tell you that you are looking for the phase 3 data to answer?

When we had the phase 2 trial, we showed the very good efficacy, and we showed the safety, but this has to be confirmed in a large group of participants. That’s why the ECLIPSE phase 3 is very large. It’s several trials to confirm efficacy and also safety, but in some of this trial also we will compare the efficacy vs bulevirtide, and also there's one trial for patients who failed bulevirtide—can they be rescued with these new regimens? Also, the size of the population will be increased, and a higher percentage of patients with compensated cirrhosis and with more severe disease will be included. We will have more robust data to confirm efficacy and also safety when we move from phase 2 to several phase 3 trials. It's a very huge and important program for the field.

References

1. Asselah T, Chatergoon MA, Streinu-Cercel A, et al. Efficacy and safety of tobevibart (VIR-3434) alone or in combination with elebsiran (VIR-2218) in participants with chronic hepatitis delta virus infection: week 96 endpoint results from the phase 2 SOLSTICE trial. Presented at: EASL Congress 2026; May 27-30, 2026; Barcelona, Spain. Abstract 429.

2. 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

3. Mathur P, Khanam A, Kottilil S. Chronic hepatitis D virus infection and its treatment: a narrative review. Microorganisms. 2024;12(11):2177. doi:10.3390/microorganisms12112177