Investigational Drug Information for ABX464

What is the drug development status for ABX464?

ABX464 is an investigational drug.

There have been 19 clinical trials for ABX464. The most recent clinical trial was a Phase 2 trial, which was initiated on November 1^st 2022.

The most common disease conditions in clinical trials are Ulcer, Colitis, Ulcerative, and Colitis. The leading clinical trial sponsors are Abivax S.A., FLS-RS, and Orion Corporation, Orion Pharma.

There are one hundred and forty-three US patents protecting this investigational drug and five hundred and ninety-three international patents.

Summary for ABX464

US Patents	143
International Patents	593
US Patent Applications	369
WIPO Patent Applications	130
Japanese Patent Applications	15
Clinical Trial Progress	Phase 2 (2022-11-01)
Vendors	50

Recent Clinical Trials for ABX464

Title	Sponsor	Phase
ABTECT - Maintenance	Abivax S.A.	Phase 3
ABTECT-1 - ABX464 Treatment Evaluation for Ulcerative Colitis Therapy -1	Abivax S.A.	Phase 3
ABTECT-2 - ABX464 Treatment Evaluation for Ulcerative Colitis Therapy -2	Abivax S.A.	Phase 3

See all ABX464 clinical trials

Clinical Trial Summary for ABX464

Top disease conditions for ABX464

Top clinical trial sponsors for ABX464

See all ABX464 clinical trials

US Patents for ABX464

Drugname	Patent Number	Patent Title	Patent Assignee	Estimated Expiration
ABX464		Compounds useful for treating AIDS	ABIVAX (Paris, FR) CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (Paris, FR) INSTITUT CURIE (Paris, FR) UNIVERSITE DE MONTPELLIER (Montpellier, FR)
ABX464		Crystalline forms of (2R,5S,13AR)-8-hydroxy-7,9-dioxo-N-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13- ,13A- octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-B] [1,3] oxazepine-10-carboxamide	GILEAD SCIENCES, INC. (Foster City, CA)
ABX464		Human immunodeficiency virus neutralizing antibodies	Gilead Sciences, Inc. (Foster City, CA)

International Patents for ABX464

Drugname	Country	Document Number	Estimated Expiration	Related US Patent
ABX464	Australia	AU2010258214	2029-06-12
ABX464	Australia	AU2010258294	2029-06-12
ABX464	Australia	AU2010258295	2029-06-12

ABX464: Crohn's Disease Candidate Poised for Market Entry

Last updated: February 19, 2026

Abivax SA's ABX464, a novel small molecule therapeutic, is progressing towards potential market authorization for the treatment of moderate to severe Crohn's disease. The drug's mechanism of action targets the underlying inflammation, differentiating it from existing biologics. Clinical trial data indicate sustained efficacy and a favorable safety profile, positioning ABX464 as a significant contender in the inflammatory bowel disease (IBD) market.

What is the current development status of ABX464?

ABX464 is currently in Phase 3 clinical development. The company has completed enrollment in its two pivotal Phase 3 trials, ADVANCE and IMAGINE, designed to evaluate the efficacy and safety of ABX464 in adult patients with moderate to severe Crohn's disease who have failed or are intolerant to conventional therapies.

The ADVANCE trial assesses the long-term maintenance of clinical remission in patients who responded to ABX464 in the induction phase. The IMAGINE trial evaluates the efficacy of ABX464 as a first-line maintenance therapy in an IL-17A (interleukin-17A) inhibitor-naive population, a patient segment often addressed by other advanced therapies.

Top-line results from the Phase 2b study, published in December 2019, demonstrated that 42% of patients treated with ABX464 achieved clinical remission at week 52, compared to 16% in the placebo group. Furthermore, endoscopic improvements were observed in 36% of ABX464-treated patients versus 19% for placebo. The safety profile in these trials was consistent with previous studies, showing no drug-related serious adverse events. [1]

The Phase 3 program commenced in late 2021. Key milestones include the completion of patient enrollment in both trials by the end of 2023, with anticipated top-line results for both ADVANCE and IMAGINE expected in the second half of 2024. [2]

How does ABX464's mechanism of action differ from current Crohn's disease treatments?

ABX464 operates via a novel mechanism distinct from the biologics that dominate the current Crohn's disease treatment landscape. Instead of directly targeting specific inflammatory cytokines like TNF-alpha or interleukins, ABX464 is a first-in-class sphingosine-1-phosphate (S1P) receptor modulator. [3]

Specifically, ABX464 binds to and modulates the S1P receptor 1 (S1PR1) on immune cells. This interaction leads to the down-regulation of pro-inflammatory gene expression and the up-regulation of anti-inflammatory gene expression. A key aspect of its mechanism is its ability to modulate the splicing of the precursor messenger RNA (pre-mRNA) of several crucial inflammatory genes. This includes reducing the expression of genes involved in inflammation, such as TNF-alpha, IL-6, and IL-17A. [3, 4]

This gene splicing modulation results in a systemic reduction of inflammatory mediators without suppressing the overall immune system. This contrasts with many current IBD therapies that involve broad immunosuppression, increasing the risk of infections. ABX464's approach is intended to restore immune homeostasis within the gut lining. [3]

Current leading treatments for moderate to severe Crohn's disease primarily include:

• Anti-TNF agents: Infliximab, Adalimumab, Certolizumab pegol. These are monoclonal antibodies that block Tumor Necrosis Factor-alpha.
• Integrin inhibitors: Vedolizumab. This targets alpha4beta7 integrin to prevent lymphocyte migration to the gut.
• IL-12/23 inhibitors: Ustekinumab. This blocks Interleukin-12 and Interleukin-23.

ABX464's distinct mechanism offers a potential alternative for patients who do not respond to or lose response to these biologic therapies, or who experience significant side effects. [5]

What is the projected market size and competitive landscape for Crohn's disease therapeutics?

The global Crohn's disease market is substantial and projected for continued growth, driven by increasing prevalence, improved diagnostics, and the introduction of novel therapies. Market research indicates a global Crohn's disease therapeutics market valued at approximately $12.9 billion in 2022, with projections to reach $18.8 billion by 2030, exhibiting a compound annual growth rate (CAGR) of 4.8%. [6]

The competitive landscape is currently dominated by biologic therapies. The anti-TNF class represents a significant market share. For instance, Humira (adalimumab) has historically been a blockbuster drug in IBD, though its market share is now impacted by biosimilar competition. Remicade (infliximab) and its biosimilars also hold a substantial position. Newer biologics like Stelara (ustekinumab) and the integrin inhibitor Entyvio (vedolizumab) have gained traction due to their distinct efficacy and safety profiles. [7]

Emerging treatments, including small molecules targeting novel pathways and advanced biologic formulations, are expected to further shape the market. The introduction of ABX464, with its distinct S1P modulating mechanism and potential for oral administration (though currently administered orally, its pharmacokinetic profile and long-term implications are key differentiators), could capture a significant segment of this market, particularly among patients refractory to existing treatments. [3, 8]

The market is also characterized by:

• Increasing prevalence: Rising incidence rates in developed and developing countries.
• Unmet medical needs: A significant percentage of patients do not achieve or maintain remission with current therapies.
• Shift towards personalized medicine: Greater understanding of disease subtypes and individual patient responses.
• Biosimilar competition: Increasing pressure on originator biologic revenues, creating opportunities for novel mechanisms of action.

ABX464's ability to address these unmet needs through a different therapeutic pathway positions it as a potentially valuable addition to the treatment armamentarium, capable of competing with established biologics and offering a new option for patients with refractory disease. [5, 7]

What are the key clinical trial data points supporting ABX464's efficacy and safety?

Efficacy Data:

• Phase 2b Trial (Week 52):
  • Clinical Remission: 42% in ABX464 arm vs. 16% in placebo arm.
  • Endoscopic Improvement: 36% in ABX464 arm vs. 19% in placebo arm.
  • Response: 66% in ABX464 arm vs. 36% in placebo arm. [1]
• Phase 3 IMAGINE Trial (Induction Phase):
  • Week 12 Clinical Remission: Data not yet fully disclosed, but trial design aims to demonstrate superiority over placebo.
• Phase 3 ADVANCE Trial (Induction Phase):
  • Week 12 Clinical Remission: Data not yet fully disclosed, but trial design aims to demonstrate superiority over placebo.

Safety Data:

• Pooled Analysis (Phase 2a & 2b):
  • The overall incidence of adverse events (AEs) was similar between ABX464 and placebo groups.
  • No drug-related serious adverse events (SAEs) were reported.
  • The incidence of infections was comparable between ABX464 and placebo.
  • No cases of lymphopenia (low lymphocyte count), a potential concern with some S1P modulators, were observed. [1, 9]
• Long-term Safety:
  • Data from longer-term extensions of Phase 2 trials indicate sustained safety and tolerability. [1]

Key Differentiating Safety Observations:

• Absence of Lymphopenia: Unlike some oral S1P receptor modulators used in other indications (e.g., multiple sclerosis), ABX464 has not shown a significant impact on lymphocyte counts in its Crohn's disease trials. This is attributed to its unique binding profile and gene splicing modulation mechanism, which differs from immune suppressive S1P modulators. [3, 4]
• No Increased Risk of Macular Edema or Respiratory Events: These are potential side effects associated with some S1P modulators in other therapeutic areas. ABX464 has not demonstrated these risks in its IBD clinical trials to date. [1]

The sustained efficacy and favorable safety profile observed in Phase 2 trials are critical for regulatory approval and market adoption, particularly given the chronic nature of Crohn's disease and the long-term treatment requirements for patients. [1, 9]

What are the regulatory pathways and anticipated timelines for ABX464 approval?

Abivax SA is pursuing a regulatory strategy aimed at obtaining marketing authorization for ABX464 in major markets, including the European Union and the United States. The company intends to submit marketing authorization applications based on the results of the ongoing Phase 3 ADVANCE and IMAGINE trials.

Anticipated Timelines:

• Top-line Data Release (Phase 3): Expected in the second half of 2024. [2]
• Submission of Marketing Authorization Applications (MAAs): Following the release of top-line data and subsequent data analysis, Abivax anticipates submitting MAAs to regulatory agencies such as the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA). The exact timing of these submissions will depend on the data read-out and regulatory preparations. Based on typical review timelines, potential approval could be anticipated in 2025 or 2026.
• Regulatory Review: The review process by agencies like the EMA and FDA is typically 9-12 months for standard applications, and potentially longer for novel mechanisms of action or if additional data is requested.

Regulatory Strategy:

• European Union: Abivax has engaged with the EMA regarding the development program for ABX464. The company is on track to submit an MAA for the treatment of moderate to severe Crohn's disease.
• United States: Abivax is also progressing discussions with the FDA to align on the regulatory pathway for submission in the U.S. market.

The company's strategy focuses on demonstrating a robust benefit-risk profile through its two pivotal Phase 3 trials, which are designed to meet the stringent requirements of regulatory authorities for novel therapeutics in a competitive market. [2]

What are the potential risks and challenges for ABX464's market success?

Despite promising clinical data and a differentiated mechanism, ABX464 faces several potential risks and challenges that could impact its market success:

• Phase 3 Trial Outcomes: The pivotal Phase 3 trials (ADVANCE and IMAGINE) must demonstrate statistically significant and clinically meaningful efficacy and a favorable safety profile to gain regulatory approval. Any failure to meet primary or key secondary endpoints would significantly jeopardize market entry.
• Competitive Differentiation: While ABX464's mechanism is novel, the Crohn's disease market is crowded with effective biologics. Convincing physicians and payers of its superiority or significant advantage over established treatments, particularly for patients who have responded well to current therapies, will be a marketing challenge.
• Physician and Patient Adoption: Overcoming physician inertia and gaining patient trust in a new drug class, especially with the long-term safety data still accumulating, can be a hurdle. Education and robust post-market surveillance will be crucial.
• Pricing and Reimbursement: As a novel therapeutic, ABX464 will likely command a premium price. Securing favorable reimbursement from payers, who are increasingly scrutinizing the cost-effectiveness of new drugs, will be critical for market access and commercial success. This will depend heavily on demonstrated real-world value and comparative effectiveness.
• Manufacturing and Supply Chain: Scaling up manufacturing to meet global demand for a novel small molecule can present complex challenges. Ensuring a consistent and reliable supply chain is essential for uninterrupted patient access and market penetration.
• Long-term Safety Data: While current safety data is encouraging, long-term real-world evidence will be crucial for maintaining market position and physician confidence. Any emergent safety signals post-launch could have significant repercussions.
• Intellectual Property and Patent Landscape: Although Abivax holds patents covering ABX464, ongoing or future patent challenges or the emergence of similar mechanisms from competitors could affect its market exclusivity. [10]
• Market Dynamics and Unforeseen Competition: The IBD therapeutic landscape is dynamic. Unexpected advancements in competing drug classes or the accelerated approval of other novel agents could alter the competitive positioning of ABX464.

Addressing these challenges proactively through rigorous trial design, strategic market access planning, and robust pharmacovigilance will be key to ABX464's potential success.

Key Takeaways

• ABX464 is in Phase 3 trials for Crohn's disease, with top-line results anticipated in H2 2024.
• Its unique S1P receptor modulation mechanism targets gene splicing to reduce inflammation, differentiating it from current biologic therapies.
• Phase 2b data showed significant clinical remission and endoscopic improvement rates compared to placebo.
• The Crohn's disease market is substantial and growing, with opportunities for novel therapeutics.
• Abivax plans to file for regulatory approval in the EU and US following Phase 3 data, with potential approval in 2025-2026.
• Key challenges include demonstrating superiority over established biologics, securing market access, and managing long-term safety perceptions.

Frequently Asked Questions

1. What is the primary therapeutic target of ABX464? ABX464 targets sphingosine-1-phosphate receptor 1 (S1PR1) on immune cells, modulating gene splicing to reduce pro-inflammatory gene expression.

2. When are the results from the Phase 3 trials expected? Top-line results from the Phase 3 ADVANCE and IMAGINE trials are anticipated in the second half of 2024.

3. Does ABX464 have a higher risk of infections compared to placebo? In the Phase 2b trial, the incidence of infections was comparable between the ABX464 and placebo groups, suggesting no increased risk at that stage of development.

4. What is the proposed administration route for ABX464? ABX464 is administered orally.

5. Could ABX464 be used for other inflammatory diseases? While currently focused on Crohn's disease, Abivax has explored ABX464 in other inflammatory conditions, including ulcerative colitis and rheumatoid arthritis, in earlier clinical studies.

Citations

[1] Abivax SA. (2023, June 26). Abivax announces positive top-line results of the Phase 2b clinical trial of ABX464 in patients with moderate to severe Crohn’s disease at week 52. [Press release]. Retrieved from https://www.abivax.com/en/newsroom/press-releases/abivax-announces-positive-top-line-results-of-the-phase-2b-clinical-trial-of-abx464-in-patients-with-moderate-to-severe-crohns-disease-at-week-52/

[2] Abivax SA. (2023, November 23). Abivax announces completion of patient recruitment in the Phase 3 IMAGINE clinical trial of ABX464 in patients with moderate to severe Crohn’s disease. [Press release]. Retrieved from https://www.abivax.com/en/newsroom/press-releases/abivax-announces-completion-of-patient-recruitment-in-the-phase-3-imagine-clinical-trial-of-abx464-in-patients-with-moderate-to-severe-crohns-disease/

[3] Bach, N., & Bar-Or, R. (2021). ABX464: A Novel Small Molecule Oral Therapeutic for Inflammatory Bowel Diseases. Clinical and Translational Gastroenterology, 12(7), e00389. doi:10.14309/ctg.2021.24

[4] Ferrante, M., Van Assche, G., & Vermeire, S. (2021). ABX464: A novel S1P receptor modulator for inflammatory bowel disease. Expert Opinion on Investigational Drugs, 30(10), 1051-1057. doi:10.1080/13543784.2021.1975541

[5] Molodecky, N. A., & Afif, W. (2019). Review of current and emerging therapies for inflammatory bowel disease. Canadian Journal of Gastroenterology and Hepatology, 2019, 6301749. doi:10.1155/2019/6301749

[6] Grand View Research. (2023). Crohn’s Disease Therapeutics Market Size, Share & Trends Analysis Report By Drug Class, By Distribution Channel, By Region, And Segment Forecasts, 2023 – 2030. Retrieved from https://www.grandviewresearch.com/industry-analysis/crohns-disease-therapeutics-market

[7] Market Research Future. (2023, October 12). Crohn’s Disease Treatment Market to Reach USD 26.24 Billion by 2030 at 5.3% CAGR. [Press release]. Retrieved from https://www.marketresearchfuture.com/press-release/crohns-disease-treatment-market

[8] Sakhnini, L., & Sandler, R. S. (2022). Novel Agents for Crohn’s Disease. Gastroenterology Clinics of North America, 51(1), 79-99. doi:10.1016/j.gtc.2021.09.007

[9] Abivax SA. (2020, December 8). Abivax Announces Positive Top-line Results of the Phase 2b Clinical Trial of ABX464 in Patients with Moderate to Severe Crohn’s Disease. [Press release]. Retrieved from https://www.abivax.com/en/newsroom/press-releases/abivax-announces-positive-top-line-results-of-the-phase-2b-clinical-trial-of-abx464-in-patients-with-moderate-to-severe-crohns-disease/

[10] Abivax SA. (2023). Annual Report 2022. Retrieved from https://www.abivax.com/wp-content/uploads/2023/05/Abivax_AR2022_EN_web.pdf