Investigational Monoclonal Antibody Shows Virologic Suppression in Chronic Hepatitis Delta – Contagion Live

Report on a Novel Combination Therapy for Chronic Hepatitis Delta and its Contribution to Sustainable Development Goal 3

A new investigational therapy for chronic hepatitis delta (CHD) shows significant promise in advancing the United Nations Sustainable Development Goal 3 (SDG 3), particularly Target 3.3, which aims to combat hepatitis by 2030. Recent 48-week data from Vir Biotechnology’s Phase 2 SOLSTICE trial, presented at the AASLD Liver Meeting and published in the New England Journal of Medicine, demonstrate that a combination of tobevibart and elebsiran achieves robust and sustained virologic suppression in patients, including those with severe disease.

Phase 2 SOLSTICE Trial Findings: A Step Towards Global Health Targets

The trial results underscore the regimen’s potential to address CHD, one of the most severe forms of viral hepatitis and a significant barrier to achieving global health and well-being targets.

Key Virologic and Clinical Outcomes

The 48-week analysis provides strong evidence of the therapy’s efficacy, a critical step in developing tools to meet the objectives of SDG 3.

• Virologic Suppression: 66% (21/32) of participants achieved a sustained undetectable hepatitis delta virus (HDV) RNA level, a primary endpoint associated with improved long-term health outcomes.
• HBsAg Reduction: Nearly 90% of participants achieved hepatitis B surface antigen (HBsAg) levels below 10 IU/mL, indicating suppression of the viral replication mechanism.
• Liver Health Improvement: 56% of participants experienced normalization of alanine aminotransferase (ALT) levels, a key indicator of reduced liver inflammation.

Safety and Tolerability Profile

The combination therapy was well-tolerated, with no Grade 3 or higher treatment-related adverse events reported and no discontinuations due to side effects. This favorable safety profile is essential for widespread adoption and ensuring patient adherence, which is fundamental to the success of public health initiatives under SDG 3.

Addressing the Global Burden of Chronic Hepatitis Delta

CHD is classified as a carcinogenic disease and is associated with rapid progression to cirrhosis and liver failure. The lack of approved therapies in many regions, including the United States, represents a significant unmet medical need and an obstacle to fulfilling SDG 3.3. The combination therapy has received multiple regulatory designations, reflecting its potential to fill this critical gap:

• U.S. Food and Drug Administration (FDA): Breakthrough Therapy and Fast Track designations.
• European Medicines Agency (EMA): PRIME and orphan designations.

The ECLIPSE Registrational Program: A Pathway to Global Access

Vir Biotechnology’s ECLIPSE program is a global registrational effort designed to confirm the safety and efficacy of the tobevibart and elebsiran combination, paving the way for regulatory submissions and eventual access for patients worldwide. This program directly supports the SDG 3 goal of ensuring access to essential medicines for all.

1. ECLIPSE 1 (NCT06903338): A Phase 3 trial comparing the combination regimen against deferred treatment.
2. ECLIPSE 2 (NCT07128550): A Phase 3 trial evaluating the efficacy of switching to the combination therapy in patients who have not achieved suppression on existing treatments.
3. ECLIPSE 3 (NCT07142811): A Phase 2b head-to-head study comparing the combination therapy with bulevirtide to support market access and reimbursement.

Therapeutic Components and Mechanism of Action

The development of this innovative therapy aligns with SDG 9, which encourages scientific research and upgrading the technological capabilities of all countries.

Tobevibart

An investigational monoclonal antibody designed to block the entry of hepatitis B and delta viruses into liver cells. It is engineered to reduce viral particles and enhance immune response, with an extended half-life for less frequent dosing.

Elebsiran

An investigational small interfering RNA (siRNA) therapy designed to degrade hepatitis B virus RNA transcripts, thereby reducing the production of HBsAg, which is essential for the HDV life cycle.

Conclusion and Future Outlook

The tobevibart-elebsiran combination therapy is advancing through the ECLIPSE registrational program, with topline results from all three studies anticipated in the first quarter of 2027. The promising Phase 2 data suggest this regimen could become a vital tool in the global fight against viral hepatitis, contributing significantly to the achievement of Sustainable Development Goal 3 and ensuring healthier lives for people affected by this severe disease.

Analysis of Sustainable Development Goals in the Article

1. Which SDGs are addressed or connected to the issues highlighted in the article?

The article on the new treatment for chronic hepatitis delta (CHD) directly and indirectly connects to several Sustainable Development Goals (SDGs) by focusing on health innovation, scientific research, and global collaboration.

• SDG 3: Good Health and Well-being: This is the most prominent SDG addressed. The entire article focuses on a medical advancement aimed at treating chronic hepatitis delta, described as “the most severe form of chronic viral hepatitis.” The development of a new, effective therapy directly contributes to improving health outcomes and combating a major communicable disease.
• SDG 9: Industry, Innovation, and Infrastructure: The article highlights significant innovation within the biotechnology and pharmaceutical industry. It details the development of advanced therapies like “an investigational broadly neutralizing monoclonal antibody (tobevibart)” and “an investigational small interfering RNA (siRNA) therapy (elebsiran).” This represents cutting-edge scientific research and technological capability in the industrial sector.
• SDG 17: Partnerships for the Goals: The development and trial of the new therapy involve collaboration. The article mentions two different companies, Vir Biotechnology and Alnylam Pharmaceuticals, who developed the two components of the combination therapy. Furthermore, the “ECLIPSE program is a global registrational effort,” indicating international cooperation to conduct clinical trials and bring the therapy to market, which aligns with the spirit of global partnerships.

2. What specific targets under those SDGs can be identified based on the article’s content?

Based on the article’s focus, several specific SDG targets can be identified:

1. Target 3.3: “By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases.”
   • Explanation: The article is explicitly about a new therapy for “chronic hepatitis delta (CHD),” a severe viral infection. The research and clinical trials are a direct effort to “combat hepatitis,” aiming to suppress and potentially cure the disease, which aligns perfectly with this target.
2. Target 3.b: “Support the research and development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect developing countries…”
   • Explanation: The article is a detailed account of the research and development process for a new medicine. It describes the results from a “phase 2 Solstice” trial and the launch of a “global registrational effort” with three Phase 3 trials (ECLIPSE 1, 2, and 3). This entire narrative is about supporting and advancing R&D for a communicable disease.
3. Target 9.5: “Enhance scientific research, upgrade the technological capabilities of industrial sectors in all countries… encouraging innovation…”
   • Explanation: The article showcases innovation in the biopharmaceutical industry. The description of tobevibart as a “broadly neutralizing monoclonal antibody” and elebsiran as a “small interfering RNA (siRNA) therapy” demonstrates the application of advanced scientific research and technology to solve a health problem.
4. Target 17.16: “Enhance the Global Partnership for Sustainable Development, complemented by multi-stakeholder partnerships that mobilize and share knowledge, expertise, technology and financial resources…”
   • Explanation: The effort described involves multiple stakeholders. Vir Biotechnology and Alnylam Pharmaceuticals are key partners. The ECLIPSE program is described as a “global registrational effort,” implying collaboration across countries with regulatory bodies like the FDA and EMA, which are mentioned as having granted special designations. This mobilization of expertise and technology across borders supports this target.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

The article provides several specific data points and descriptions that can serve as indicators of progress towards the identified targets.

• For Target 3.3 (Combat hepatitis): The article provides direct clinical outcome measures that function as progress indicators.
  • Indicator: Virologic response rate in patients. The article states, “66% (21/32) of participants achieved sustained hepatitis delta virus (HDV) RNA target not detected (TND) at Week 48.”
  • Indicator: Normalization of liver biomarkers. It is mentioned that “alanine aminotransferase (ALT) levels normalized in 56% of participants.”
  • Indicator: Suppression of related viral markers. The text notes, “Nearly 90% reached hepatitis B surface antigen (HBsAg) levels below 10 IU/mL.”
• For Target 3.b (Support R&D): The article implies progress in R&D through several milestones.
  • Indicator: Advancement of new drugs through clinical trial phases. The article states the combination therapy has completed a Phase 2 trial and is “now advancing through Vir’s ECLIPSE registrational program, which includes three randomized, controlled Phase 3 trials.”
  • Indicator: Regulatory recognition of new therapies. The article notes the therapy has received “Breakthrough Therapy and Fast Track designations from the FDA and PRIME and orphan designations from the EMA,” indicating its significance and potential.
• For Target 9.5 (Enhance scientific research and innovation):
  • Indicator: Development of novel therapeutic platforms. The article describes the specific innovative technologies being used: a “monoclonal antibody platform” and “small interfering RNA (siRNA) therapy.”
• For Target 17.16 (Global Partnership):
  • Indicator: Establishment of international, multi-stakeholder research programs. The “ECLIPSE program” is described as a “global registrational effort” involving trials in the “U.S. and other regions,” demonstrating a partnership to achieve a common goal.

4. Table of SDGs, Targets, and Indicators

Source: contagionlive.com