Introduction to ABI-H0731
ABI-H0731, developed by Assembly Biosciences, is a novel core inhibitor targeted at treating chronic hepatitis B virus (HBV) infection. This drug belongs to a new class of direct-acting HBV antivirals known as Core Protein Allosteric Modifiers (CpAMs), designed to target the HBV core protein involved in multiple steps of the HBV life cycle[2][4].
Clinical Trial Progress
Phase 2 Clinical Trials
ABI-H0731 has been undergoing Phase 2 clinical trials, where it has shown promising results. In these trials, ABI-H0731, when administered with nucleos(t)ide analogue reverse transcriptase inhibitor (NrtI) therapy, has demonstrated statistically superior antiviral activity in HBV DNA suppression compared to NrtI therapy alone. The drug has also shown significant declines in HBV pregenomic RNA (pgRNA), which may indicate decreased covalently closed circular DNA (cccDNA) levels[1][4].
Combination Therapies
Assembly Biosciences is exploring the efficacy of ABI-H0731 in combination with other therapeutic agents. A randomized, multi-center, open-label Phase 2 clinical trial is planned to evaluate the safety, pharmacokinetics, and antiviral activity of the triple combination of ABI-H0731, RNA interference (RNAi) therapeutic AB-729 from Arbutus Biopharma, and an NrtI. This trial aims to enroll approximately 60 virologically-suppressed patients with HBeAg negative or positive chronic HBV infection and will include a 48-week dosing period followed by a 24-week follow-up[1].
Transition to Finite and Curative Therapies
Assembly Biosciences has shifted its focus from chronic suppressive therapies to finite and curative HBV therapies. As part of this strategy, the company is prioritizing its next-generation core inhibitors, including ABI-H0731, and exploring combinations with complementary mechanisms of action to achieve a functional cure for HBV[4].
Safety and Efficacy
Safety Profile
In ongoing clinical trials, ABI-H0731 has been well-tolerated when administered with NrtI therapy. The drug has shown a favorable safety profile, which is crucial for long-term treatment of chronic HBV infection[1][3].
Efficacy Data
ABI-H0731 has demonstrated significant reductions in HBV DNA and pgRNA levels. The reduction in pgRNA is particularly noteworthy as it may indicate a decrease in cccDNA levels, a key factor in achieving a functional cure for HBV. Approximately 88% of participants in the Phase 2 study are projected to meet criteria for stopping therapy, suggesting a high potential for sustained virologic response (SVR)[3][4].
Market Projection
Global Need for HBV Treatments
Hepatitis B remains a significant global public health threat, with over 250 million people worldwide living with chronic HBV infections. The current treatment options, while effective in suppressing the virus, require lifelong administration and do not offer a cure. This unmet medical need creates a substantial market opportunity for innovative treatments like ABI-H0731[5].
Competitive Landscape
The HBV treatment market is becoming increasingly competitive with several new drugs in various stages of clinical development. However, ABI-H0731's unique mechanism of action and promising clinical data position it favorably. Other notable competitors include Gilead’s GS-9688, Johnson & Johnson’s JNJ-6379, and Ionis’ IONIS-HBVLRx, but ABI-H0731's combination therapy approach and focus on finite and curative treatments could differentiate it in the market[5].
Regulatory Status
ABI-H0731 has received Fast Track designation from the US Food and Drug Administration (FDA), which could expedite its development and approval process. This designation is a significant milestone, indicating the FDA's recognition of the drug's potential to address an unmet medical need[3][4].
Future Directions
Additional Cohorts and Combinations
Assembly Biosciences plans to add additional cohorts to the ongoing clinical trials to evaluate other patient populations and combinations. This includes evaluating the combination of ABI-H0731 with interferon (peg-IFNα) and other complementary mechanisms of action to enhance antiviral activity and move towards a functional cure for HBV[1][4].
Collaboration and Licensing
The company has partnered with BeiGene for the exclusive development and commercialization of its HBV core inhibitors, including ABI-H0731, in China. This collaboration includes significant upfront and milestone payments, as well as royalties on sales, highlighting the market potential of ABI-H0731 in regions with high HBV prevalence[3].
Key Takeaways
- Clinical Progress: ABI-H0731 is in Phase 2 clinical trials, showing superior antiviral activity and a favorable safety profile.
- Combination Therapies: The drug is being evaluated in combination with RNAi therapeutic AB-729 and NrtI to enhance efficacy.
- Market Need: The global demand for effective HBV treatments is high, with over 250 million people affected.
- Competitive Advantage: ABI-H0731's unique mechanism and focus on finite and curative therapies differentiate it in the market.
- Regulatory Status: The drug has received Fast Track designation from the FDA, potentially expediting its approval.
FAQs
Q: What is ABI-H0731, and how does it work?
A: ABI-H0731 is a core inhibitor that targets the HBV core protein, involved in multiple steps of the HBV life cycle. It belongs to a new class of direct-acting HBV antivirals known as Core Protein Allosteric Modifiers (CpAMs).
Q: What are the current clinical trial stages for ABI-H0731?
A: ABI-H0731 is currently in Phase 2 clinical trials, evaluating its safety, pharmacokinetics, and antiviral activity, both as a standalone treatment and in combination with other therapies.
Q: How does ABI-H0731 compare to current HBV treatments?
A: ABI-H0731 has shown statistically superior antiviral activity compared to current NrtI therapies alone and has the potential to offer a more finite treatment duration, moving towards a functional cure for HBV.
Q: What are the safety and efficacy findings for ABI-H0731?
A: The drug has been well-tolerated and has demonstrated significant reductions in HBV DNA and pgRNA levels, indicating a potential decrease in cccDNA levels.
Q: What is the market potential for ABI-H0731?
A: Given the global need for effective HBV treatments and its promising clinical data, ABI-H0731 has significant market potential, especially with its focus on finite and curative therapies.
Sources
- Assembly Biosciences and Arbutus Biopharma Announce Clinical Trial Plans for HBV Core Inhibitor and RNAi Therapeutic Combination. Investor.arbutusbio.com.
- Global Hepatitis B Market Size. DelveInsight Business Research.
- Assembly Biosciences, Inc - ASMB STOCK NEWS. Stocktitan.net.
- Assembly Biosciences Updates Pipeline Strategy, Focusing on Finite and Curative Therapies for Chronic Hepatitis B Virus Infection. Biospace.com.
- Hepatitis B cure: a consideration of HBV ABI-H0731 drug. Pharmaceutical-technology.com.
