Vir Biotechnology Presents Positive Chronic Hepatitis Delta Clinical Trial Data and Announces Initiation of Phase 3 Registrational Program
– Monthly tobevibart and elebsiran combination achieves rapid 100% virologic suppression at Week 24, sustained through Week 60 –
– Undetectable HDV RNA in 41% of participants at Week 24, increasing to 64% by Week 36 and up to 80% by Week 60 across cohorts –
– Combination well-tolerated: no treatment-related severe AEs, treatment-related discontinuations or ALT flares –
– Following a recent FDA meeting, Phase 3 ECLIPSE registrational program to begin in the first half of 2025 –
– New data presented at AASLD The Liver Meeting. Investor conference call
These data were presented in an oral session at the American Association for the Study of Liver Diseases (AASLD)
CHD is a chronic inflammatory liver disease caused by HDV1. It is the most severe form of chronic viral hepatitis2 and on average, people living with CHD will progress to cirrhosis and liver failure within 5 years3. There is no approved treatment in
“Achieving HDV RNA suppression with a safe, well-tolerated, and conveniently dosed treatment could be transformative for people living with hepatitis delta. The impressive rates of virologic suppression seen in the SOLSTICE Phase 2 data suggest that tobevibart and elebsiran have the potential to significantly improve patient outcomes,” said
Primary Endpoint Analysis from the Phase 2 SOLSTICE Trial
Clinical trial participants were randomized to receive tobevibart 300 mg monotherapy every two weeks (n=33) or a combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (combination de novo arm, n=32). In addition, the participants from previous tobevibart or elebsiran monotherapy cohorts could rollover to receive the combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (combination rollover, n=13). Rates of virologic suppression were evaluated at Week 24, and further assessed at Weeks 36, 48 and 60 in those participants that had reached each timepoint. Further monitoring will continue up to 192 weeks.
Rapid and Sustained Virologic Suppression – 100% of participants across combination arms achieved an HDV RNA ≥2 log10 decrease or below limit of detection (LOD) at Week 24, and this rate was sustained over time in all participants at Weeks 36 (22/22) and those in the rollover cohort that reached Week 60 (5/5).
HDV RNA TND was achieved in 41% (13/32) of participants across combination arms at Week 24 and this rose to 64% (14/22) at Week 36. By week 60, this had risen further with 80% (4/5) of participants in the rollover cohort having achieved no detectable viral RNA.
Approximately 90% of participants receiving the combination achieved reductions in hepatitis B surface antigen (HBsAg) values below <10 IU/mL at Week 24, with sustained responses at later time points. This indicates suppression of the key biologic mechanisms that HDV requires for viral replication.
ALT Normalization – Alanine aminotransferase (ALT) decreased in most participants between Day 1 and Week 24 and normalized in 47% (15/32) of participants in the combination de novo cohort and 56% (5/9) in the rollover cohort by Week 24. These rates were sustained at Week 36.
Combined Endpoints – The protocol defined combined endpoint of HDV RNA decrease ≥ 2 log10 compared to baseline or HDV RNA below LOD and ALT normalization at Week 24 was observed in 47% (15/32) of participants in the combination de novo arm.
The more stringent composite endpoint of HDV RNA TND and ALT normalization was achieved in 19% (6/32) of participants in the combination de novo arm at Week 24, which increased to 27% (6/22) by Week 36. This trend was reflected in the combination rollover cohort in which 33% (3/9) of participants achieved this endpoint at Week 24 and 40% (2/5) at Week 60. Rates of HDV RNA suppression and ALT normalization were similar between non-cirrhotic and cirrhotic participants across combination arms.
Safety Profile – The safety profile of tobevibart and elebsiran is consistent with previous studies. Treatment-emergent adverse events (TEAEs) were generally mild or moderate and transient across all treatment groups, with influenza-like illness being the most common event. No ALT flares were observed. There were no study-related discontinuations in the combination arms, and no treatment-related severe adverse events (SAEs) were reported.
“People living with hepatitis delta in the US have no approved treatment options, and therapies are limited globally. At
Phase 3 Registrational ECLIPSE Program
Following a meeting with the FDA,
-
ECLIPSE 1 will assess the efficacy and safety of tobevibart and elebsiran compared to deferred treatment in regions such as the
U.S. where bulevirtide is not available or its use is limited.
- ECLIPSE 2 will evaluate the efficacy and safety of switching to tobevibart and elebsiran in people with CHD who have not achieved viral suppression with bulevirtide therapy.
- ECLIPSE 3 is a Phase 2b head-to-head trial to evaluate tobevibart and elebsiran compared with bulevirtide in bulevirtide-naïve patients.
In
Investor Conference Call
About the Phase 2 SOLSTICE Trial
SOLSTICE is a Phase 2 study to evaluate the safety, tolerability, and efficacy of tobevibart, alone or in combination with elebsiran, in people with chronic hepatitis delta. This Phase 2 study is a multi-center, open-label, randomized study. Primary endpoints include proportion of participants with undetectable hepatitis delta virus (HDV) RNA (defined as HDV RNA equal or greater than 2 log10 decrease from baseline or below limit of detection) up to week 24, alanine aminotransferase (ALT) normalization (defined as ALT below upper limit of normal) up to week 24, and treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) up to 118 weeks. Secondary endpoints include proportion of participants with undetectable HDV RNA and different timepoints and up to 192 weeks. More information about this trial can be found at clinicaltrials.gov (NCT05461170).
About Tobevibart and Elebsiran
Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen. It is designed to inhibit the entry of hepatitis B and hepatitis delta viruses into hepatocytes, and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart, which incorporates Xencor’s Xtend™ and other Fc technologies, has been engineered to have an extended half-life and was identified using Vir Biotechnology’s proprietary monoclonal antibody discovery platform. Tobevibart is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta.
Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. Current data indicates that it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. Elebsiran is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis B and patients with chronic hepatitis delta. It is the first asset in Vir Biotechnology’s collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical studies.
Tobevibart and elebsiran are also being evaluated as a potential functional cure for chronic hepatitis B.
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References:
1
2 WHO Hepatitis Delta Factsheet – Hepatitis D (who.int), accessed
3
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “will,” “plan,” “potential,” “aim,” “expect,” “anticipate,” “promising” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Vir Biotechnology’s expectations and assumptions as of the date of this press release. Forward-looking statements contained in this press release include, but are not limited to, statements regarding Vir Biotechnology’s strategy and plans, the potential clinical effects of tobevibart and elebsiran, the potential benefits, safety and efficacy of tobevibart and elebsiran, the timing, nature and significance of data from Vir Biotechnology’s multiple ongoing trials evaluating tobevibart and elebsiran, Vir Biotechnology’s plans and expectations for its CHD and CHB programs, and risks and uncertainties associated with drug development and commercialization. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data or results observed during clinical trials or in data readouts; the occurrence of adverse safety events; risks of unexpected costs, delays or other unexpected hurdles; difficulties in collaborating with other companies; successful development and/or commercialization of alternative product candidates by Vir Biotechnology’s competitors; changes in expected or existing competition; delays in or disruptions to Vir Biotechnology’s business or clinical trials due to geopolitical changes or other external factors; and unexpected litigation or other disputes. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented. Other factors that may cause actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Vir Biotechnology’s filings with the
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