Tobevibart Monotherapy and Combination Therapy with Elebsiran Achieved High Virologic Response and ALT Normalization in People Living with the Hepatitis Delta Virus After 12 and 24 Weeks of Treatment

Rhea-AI Summary

Vir Biotechnology announced promising preliminary phase 2 data from its SOLSTICE trial for hepatitis delta treatment. The study evaluates tobevibart, a monoclonal antibody, and elebsiran, a small interfering RNA, as monotherapy and combination therapy.

Key findings include high virologic response rates and ALT normalization at 12 and 24 weeks. Combination therapy showed 100% virologic response at both 12 and 24 weeks, while tobevibart monotherapy had 73% and 55% at these intervals. Most adverse events were mild and transient without serious occurrences.

Further data will be presented at the EASL Congress 2024, with a conference call scheduled for June 5, 2024.

Positive

• High virologic response rates: 100% for combination therapy at both 12 and 24 weeks.
• Significant ALT normalization rates: 64% for combination therapy at 24 weeks.
• Tobevibart and elebsiran combination therapy shows promising results for hepatitis delta treatment.
• Most adverse events were mild and transient with no serious adverse occurrences.
• Potential transformative treatment for a disease with high unmet medical needs.

Negative

• Tobevibart monotherapy showed lower virologic response rates: 73% at 12 weeks and 55% at 24 weeks.
• Discontinuation of 4 participants from the trial due to adverse events and withdrawal.
• No ALT normalization observed in half of the combination therapy group at 12 weeks.

Insights

Medical Research Analyst

The recent preliminary data from Vir Biotechnology’s Phase 2 SOLSTICE clinical trial shows strong potential for tobevibart and elebsiran as treatments for chronic hepatitis delta virus (HDV). Both monotherapy and combination treatments demonstrated high virologic response rates and ALT normalization, which are important indicators of liver health.

Tobevibart and elebsiran showcased effective reduction in HDV RNA levels, with 100% virologic response in combination therapy by week 24. Single-agent tobevibart also performed well, achieving a 55% response rate in the same timeframe. The normalization of ALT levels—seen in up to 64% of combination therapy participants—suggests notable improvement in liver function.

The findings are particularly significant due to the high unmet medical need in chronic HDV, a disease often leading to severe complications like cirrhosis and liver cancer. The absence of serious adverse events and treatment-related complications further adds to the promise of these therapies.

For retail investors, the major takeaway is the potential for these treatments to fill a substantial gap in the current market, potentially paving the way for faster regulatory approvals and increased market share for Vir Biotechnology.

Rating: 1

Market Research Analyst

The preliminary results from the SOLSTICE trial indicate significant progress for Vir Biotechnology in the hepatitis delta treatment market. The high virologic response rates observed in the study, especially the 100% response for combination therapy at various checkpoints, suggest a competitive edge over current treatment options.

Given the limited treatment options available for chronic HDV, successful development of tobevibart and elebsiran could position Vir Biotechnology as a leader in this niche market. This progress may attract attention from investors, particularly those interested in biotech companies addressing niche, unaddressed medical needs.

Another factor to consider is the strategic timing of this announcement ahead of major conferences, which could drive positive sentiment and visibility for the company among investors and potential partners in the pharmaceutical industry.

In the short term, this data could trigger a positive stock movement as the market responds to the promising efficacy and safety results. Long-term implications include potential FDA approval and market capture, enhancing the company's revenue streams.

Rating: 1

– Preliminary Phase 2 SOLSTICE trial data reinforce the potential of both regimens to be transformative treatments in an area of high unmet medical need –

– Conference call scheduled for June 5, 2024, at 6:00 a.m. ET / 12:00 p.m. CEST –

SAN FRANCISCO--(BUSINESS WIRE)-- Vir Biotechnology, Inc. (Nasdaq: VIR) today announced new preliminary data from its Phase 2 SOLSTICE hepatitis delta clinical trial evaluating tobevibart, an investigational monoclonal antibody, and elebsiran, an investigational small interfering ribonucleic acid, for the treatment of people living with chronic hepatitis delta. Preliminary data from the Phase 2 trial show treatment with tobevibart alone or in combination with elebsiran was generally well tolerated and participants achieved high rates of virologic response at weeks 12 and 24, durable virologic response through 48 weeks, and high rates of ALT normalization.

The Company will host an investor conference call on June 5 at 6:00 a.m. ET / 12:00 p.m. CEST to discuss these data. Originally accepted as a late-breaker poster, these data will be presented in more detail in an oral presentation on June 8 at the European Association for the Study of the Liver, EASL™ Congress 2024.

Preliminary data from the six participants reported on at the 2023 American Association for the Study of Liver Diseases (AASLD) The Liver Meeting^® demonstrated sustained virologic response:

• These participants received 12 weeks of either tobevibart or elebsiran monotherapy and then rolled over into combination therapy. All 6 participants remain on treatment. At the time of the analysis, 5 out of the 6 participants had reached 48 weeks of combination therapy and 1 had reached 40 weeks of combination therapy.
  • All 6 participants showed sustained virologic response at time of last visit
  • 100% (6 of 6) achieved HDV RNA < limit of detection (LOD) or ≥ 2 log₁₀ IU/mL decrease from baseline
  • 50% (3 of 6) achieved ALT normalization
  • 50% (3 of 6) achieved the combined endpoint*
  • Furthermore, 100% (6 of 6) achieved HDV RNA < the lower limit of quantification (LLOQ), 100% (6 of 6) achieved HDV RNA < LOD, and 83% (5 of 6) achieved HDV RNA target not detected (TND)
• The majority of adverse events were Grade 1-2 and transient in nature with no reported serious adverse events, no ALT flares and no Grade 2 or higher elevations in liver function tests (LFTs) were observed.

Preliminary de novo combination of tobevibart + elebsiran (monthly dosing) data demonstrated rapid and high rates of virologic suppression and ALT normalization:

• Week 12: Among 27 participants
  • 100% (27 of 27) achieved HDV RNA < LOD or ≥ 2 log₁₀ IU/mL decrease from baseline
  • 44% (12 of 27) achieved ALT normalization
  • 44% (12 of 27) achieved the combined endpoint*
  • Furthermore, 52% (14 of 27) achieved HDV RNA < LLOQ, 37% (10 of 27) achieved HDV RNA < LOD, and 15% (4 of 27) achieved HDV RNA TND
• Week 24: Among 11 participants
  • 100% (11 of 11) achieved HDV RNA < LOD or ≥ 2 log₁₀ IU/mL decrease from baseline
  • 64% (7 of 11) achieved ALT normalization
  • 64% (7 of 11) achieved the combined endpoint*
  • Furthermore, 100% (11/11) achieved HDV RNA < LLOQ, 91% (10 of 11) achieved HDV RNA < LOD, and 55% (6 of 11) achieved HDV RNA TND
• Similar rates of virologic suppression and ALT normalization were observed in participants who are non-cirrhotic (n=6) and those with compensated cirrhosis (CPT-A, n=5).
• The majority of adverse events were Grade 1-2 and transient in nature with no treatment-related serious adverse events, no ALT flares and no Grade 2 or higher elevations in LFTs were observed.

Preliminary tobevibart monotherapy (twice monthly dosing) data demonstrated high rates of virologic suppression and ALT normalization:

• Week 12: Among 26 participants
  • 73% (19 of 26) achieved HDV RNA < LOD or ≥ 2 log₁₀ IU/mL decrease from baseline
  • 54% (14 of 26) achieved ALT normalization
  • 38% (10 of 26) achieved the combined endpoint*
  • Furthermore, 27% (7 of 26) achieved HDV RNA < LLOQ, 19% (5 of 26) achieved HDV RNA < LOD, and 8% (2 of 26) achieved HDV RNA TND
• Week 24: Among 11 participants
  • 55% (6 of 11) achieved HDV RNA < LOD or ≥ 2 log₁₀ IU/mL decrease from baseline
  • 64% (7 of 11) achieved ALT normalization
  • 55% (6 of 11) achieved the combined endpoint*
  • Furthermore, 55% (6 of 11) achieved HDV RNA < LLOQ, 46% (5 of 11) achieved HDV RNA <LOD, and 18% (2 of 11) achieved HDV RNA TND
• The majority of adverse events were Grade 1-2 and transient in nature with no serious adverse events, no ALT flares and no Grade 2 or higher elevations in LFTs were observed.

“As the most severe form of viral hepatitis, chronic hepatitis delta poses a significant threat to millions worldwide and often leads to life-threatening complications such as cirrhosis and liver cancer. Despite the urgent need for effective and convenient therapies, the options for patients remain limited,” said Tarik Asselah, M.D., Ph.D., Professor of Hepatology at the Hôpital Beaujon, APHP, Clichy, France, and at the University of Paris, and Head of Viral Hepatitis at INSERM UMR1149, France. “The impressive reduction in HDV RNA observed in the preliminary SOLSTICE trial data surpasses any previous therapy reported to date and highlights the promise of tobevibart and elebsiran in addressing this critical unmet need.”

Phase 2 SOLSTICE Trial Preliminary Data Summary Table:

	Combo Q4W rollover (monthly)1 N = 6			De novo combination of tobevibart + elebsiran (monthly) N = 32		tobevibart monotherapy (Q2W) N = 33
	Week 12 n=6	Week 24 n=6	Week 48 n=52	Week 12 n=27	Week 24 n=11	Week 12 n=263	Week 24 n=113
1) n (%) Virologic Response (HDV RNA < LOD or ≥ 2 log10 IU/mL decrease from baseline)	6/6 (100%)	6/6 (100%)	5/5 (100%)	27/27 (100%)	11/11 (100%)	19/26 (73%)	6/11 (55%)
2) n (%) HDV RNA < LLOQ	6/6 (100%)	6/6 (100%)	5/5 (100%)	14/27 (52%)	11/11 (100%)	7/26 (27%)	6/11 (55%)
3) n (%) HDV RNA < LOD	5/6 (83%)	5/6 (83%)	5/5 (100%)	10/27 (37%)	10/11 (91%)	5/26 (19%)	5/11 (46%)
4) n (%) HDV RNA TND	4/6 (67%)	3/6 (50%)	4/5 (80%)	4/27 (15%)	6/11 (55%)	2/26 (8%)	2/11 (18%)
5) n (%) ALT normalization	2/6 (33%)	2/6 (33%)	2/5 (40%)	12/27 (44%)	7/11 (64%)	14/26 (54%)	7/11 (64%)
6) n (%) Combined Endpoint (CE) (Rows 1 + 5)	2/6 (33%)	2/6 (33%)	2/5 (40%)	12/27 (44%)	7/11 (64%)	10/26 (38%)	6/11 (55%)
1 For Combo Q4W rollover baseline: Day 1 of combination therapy, 12 weeks additionally on monotherapy
2 Rollover cohort: All 6 participants remain on therapy. At the time of analysis, 5 participants were at week 48 and 1 was at week 40 of the combination therapy. The participant at week 40 has achieved HDV RNA TND, ALT normalization, and the CE
3 Responses on ITT basis and includes 4 participants who discontinued treatment, 2 due to adverse events and 2 who withdrew from the trial
HDV: Hepatitis Delta Virus
RNA: RiboNucleic Acid
LLOQ: lower limit of quantification = 63 IU/mL
LOD: limit of detection = 14 IU/mL
TND: target not detected (undetectable viral load)

The Company is on track to report additional 24-week treatment data for all approximately 60 SOLSTICE participants in the fourth quarter of 2024.

“The preliminary data from our Phase 2 hepatitis delta trial provide compelling evidence that either tobevibart and elebsiran in combination or tobevibart as monotherapy could represent a transformative treatment option for individuals living with this devastating disease,” said Marianne De Backer, M.Sc., Ph.D., MBA, Vir’s Chief Executive Officer. “Recognizing the critical need for improved treatment options, we are committed to working closely with regulatory authorities to determine the next steps to bring these promising candidates to patients in need as expeditiously as possible.”

EASL oral presentation details:

• Title: Efficacy and safety of tobevibart (VIR-3434) alone or in combination with elebsiran (VIR-2218) in participants with chronic hepatitis delta virus infection: preliminary results from the phase 2 SOLSTICE trial in non-cirrhotic and compensated cirrhotic participants (OS-127)
  Session: Viral hepatitis B/D: Therapy
  Date: Saturday, June 8
  Time: 11:45 a.m. CEST (5:45 a.m. EDT)
  Presenter: Tarik Asselah, M.D., Ph.D., Professor of Hepatology at the Hôpital Beaujon, APHP, Clichy, France, and at the University of Paris, and Head of Viral Hepatitis at INSERM UMR1149, France

A live webcast of the June 5 investor call will be made available on https://investors.vir.bio and a recording will be archived there for 30 days.

The EASL oral scientific presentation will be made available under Events & Presentations in the Investors section of the Vir website following the presentation on June 8^th.

About the Phase 2 SOLSTICE Trial

The SOLSTICE trial (NCT05461170) is evaluating the safety, tolerability and efficacy of tobevibart and elebsiran for the treatment of people living with chronic hepatitis delta. One cohort is evaluating the combination of tobevibart and elebsiran dosed every 4 weeks with a second cohort evaluating tobevibart monotherapy every 2 weeks. Approximately 50% of participants have compensated cirrhosis.

About Tobevibart (VIR-3434)

Tobevibart is an investigational subcutaneously administered antibody designed to inhibit entry of hepatitis B and hepatitis delta viruses into hepatocytes, neutralize both hepatitis B virus and hepatitis delta virus virions and to reduce the level of virions 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’s proprietary monoclonal antibody discovery platform.

About Elebsiran (VIR-2218)

Elebsiran is an investigational subcutaneously administered 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. Vir believes it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. It is the first siRNA in the clinic to include Enhanced Stabilization Chemistry Plus (ESC+) technology to enhance stability and minimize off-target activity, which potentially could result in an increased therapeutic index. Elebsiran is the first asset in the Company’s collaboration with Alnylam Pharmaceuticals, Inc. to enter clinical trials.

About Vir Biotechnology, Inc.

Vir Biotechnology, Inc. is an immunology company focused on powering the immune system to transform lives by treating and preventing infectious diseases and other serious conditions, including viral-associated diseases. Vir has assembled two technology platforms that are designed to modulate the immune system by exploiting critical observations of natural immune processes. Its current clinical development pipeline consists of product candidates targeting hepatitis delta and hepatitis B viruses, and human immunodeficiency virus. Vir has several preclinical candidates in its pipeline, including those targeting influenza A and B, COVID-19, RSV/MPV and HPV. Vir routinely posts information that may be important to investors on its website.

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’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’s strategy and plans, the potential clinical effects of tobevibart and elebsiran, the potential benefits, safety and efficacy of tobevibart and elebsiran, data from Vir’s multiple ongoing trials evaluating tobevibart and elebsiran, Vir’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’s competitors; changes in expected or existing competition; delays in or disruptions to Vir’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’s filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as required by law, Vir assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

^* The combined endpoint (CE) is a combined response of an undetectable HDV RNA level, or a level that decreased by at least 2 log₁₀ IU per milliliter from baseline, and normalization of the alanine aminotransferase (ALT) level.

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Media

Carly Scaduto

Senior Director, External Communications

cscaduto@vir.bio

+1 314-368-5189

Investors

Richard Lepke

Senior Director, Investor Relations

rlepke@vir.bio

+1 978-973-9986

Source: Vir Biotechnology, Inc.

FAQ

What is the virologic response of Vir Biotechnology's hepatitis delta treatment at 12 and 24 weeks?

The combination therapy achieved 100% virologic response at both 12 and 24 weeks. Tobevibart monotherapy showed 73% at 12 weeks and 55% at 24 weeks.

What are the ALT normalization rates for the SOLSTICE trial at 24 weeks?

The ALT normalization rate for combination therapy was 64% at 24 weeks. Tobevibart monotherapy had a 64% ALT normalization rate at the same interval.

Were there any serious adverse events reported in the SOLSTICE trial?

No serious adverse events were reported. The majority of adverse events were mild and transient.

When will Vir Biotechnology present detailed results from the SOLSTICE trial?

Detailed results will be presented at the EASL Congress on June 8, 2024.

What is the next step for Vir Biotechnology's hepatitis delta treatment after the preliminary phase 2 data?

Vir Biotechnology plans to work closely with regulatory authorities to determine the next steps for bringing the treatment to patients.