Afimkibart
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | TNFSF15 |
| Clinical data | |
| Drug class | Human IgG1 monoclonal antibody |
| Identifiers | |
| CAS Number | |
| PubChem SID | |
| UNII | |
| Chemical and physical data | |
| Formula | C6472H9968N1742O2030S48 |
| Molar mass | 146199.98 g·mol−1 |
Afimkibart (also known as PF-06480605, RVT-3101, or RG6631) is an investigational human IgG1 monoclonal antibody developed by Roche, formerly by Pfizer and Roivant Sciences, for the treatment of inflammatory diseases, including inflammatory bowel disease (ulcerative colitis, Crohn’s disease) and atopic dermatitis.[1][2][3][4][5] It targets Tumor Necrosis Factor-like Ligand 1A (TL1A, also known as TNFSF15 or VEGI), a pro-inflammatory cytokine implicated in immune dysregulation and chronic inflammation.[6][7] As of June 2025, afimkibart is in Phase III trials for ulcerative colitis and Phase II trials for Crohn’s disease and atopic dermatitis, demonstrating promising efficacy and safety.[8][1]
Mechanism of action
[edit]Afimkibart binds with high affinity to TL1A, a cytokine that drives inflammation in immune-mediated disorders by activating immune cells and promoting pro-inflammatory cytokine production.[6] By neutralizing TL1A, afimkibart prevents its interaction with receptors on immune cells, inhibiting downstream inflammatory pathways.[9] This reduces localized and systemic inflammation, alleviating symptoms of diseases like ulcerative colitis, Crohn’s disease, and atopic dermatitis.[6] Its mechanism is distinct from other biologics, such as anti-TNF agents, offering a novel approach to managing type 2 and non-type 2 inflammation.[4][1]
Development history
[edit]Afimkibart, initially developed by Pfizer as PF-06480605, began Phase I trials in December 2013 to assess safety and pharmacokinetics.[4][1]
In 2016, Pfizer initiated Phase II trials for inflammatory bowel disease.[4] In 2021, Roivant Sciences acquired the drug, renaming it RVT-3101, to advance its development for ulcerative colitis.[10] Key milestones include:
- January 2023: Roivant announced positive results from the TUSCANY-2 Phase IIb trial’s induction period for ulcerative colitis, showing statistically significant efficacy.[4]
- June 2023: A Phase II trial for Crohn’s disease (NCT05910528) was initiated.[4][11]
- October 2023: Roche acquired Telavant Holdings, a Roivant subsidiary, for $7.1 billion, securing rights to afimkibart (designated RG6631) in the United States and Japan.[10]
- September 2024: Two Phase III trials for ulcerative colitis (NCT06588855, NCT06589986) began, sponsored by Roche.[8][2][3]
Roche’s acquisition has accelerated afimkibart’s development, with plans to expand trials for atopic dermatitis and other indications.[12]
Clinical trials
[edit]Afimkibart is undergoing clinical trials for multiple indications, with significant progress in ulcerative colitis, Crohn’s disease, and atopic dermatitis.[4]
Ulcerative colitis
[edit]The TUSCANY Phase IIa trial (NCT03124121), a multicenter, open-label study, evaluated afimkibart (500 mg IV every two weeks for seven doses) in patients with moderate-to-severe ulcerative colitis.[9][13] Results showed endoscopic improvement in 38.2% of participants at week 14, with an acceptable safety profile.[9]
The TUSCANY-2 Phase IIb trial (NCT04090411) demonstrated significant clinical remission and endoscopic response in the induction phase by January 2023.[4][5]
Two Phase III trials, initiated in September 2024 (NCT06588855, NCT06589986), are assessing long-term efficacy and safety in ulcerative colitis, with primary endpoints including clinical remission and mucosal healing.[8][2][3]
Crohn’s disease
[edit]A Phase II trial (NCT05910528) for Crohn’s disease began in June 2023, evaluating afimkibart’s efficacy in patients with moderate-to-severe disease.[4] Primary endpoints include clinical response and endoscopic improvement, with results expected in 2026.[11][12]
Atopic dermatitis
[edit]Afimkibart is in Phase II development for atopic dermatitis, with trials assessing subcutaneous administration in patients with moderate-to-severe disease.[12][4]
Pharmacokinetics
[edit]Afimkibart is administered intravenously or subcutaneously, with a mean elimination half-life of 18.4 days (150 mg dose) to 19.1 days (450 mg dose), showing dose-proportional exposure.[14]
As a monoclonal antibody, it distributes primarily in vascular and interstitial compartments and is degraded via proteolytic pathways, minimizing drug-drug interactions.[6] Pharmacokinetic data from Phase I trials in Japanese patients confirmed its suitability for global development.[14]
Adverse effects
[edit]Clinical trials, including the TUSCANY Phase IIa study, reported an acceptable safety profile for afimkibart.[9] Common treatment-emergent adverse events included exacerbations of ulcerative colitis and arthralgia (joint pain), with rare serious adverse events and no reported deaths or malignancies.[9]
Regulatory status
[edit]As of June 2025, afimkibart remains an investigational drug without approval from regulatory bodies like the U.S. Food and Drug Administration (FDA) or European Medicines Agency (EMA).[4] Roche anticipates regulatory submissions for ulcerative colitis by 2027, pending Phase III trial outcomes.[8]
References
[edit]- ^ a b c d Banfield C, Rudin D, Bhattacharya I, Goteti K, Li G, Hassan-Zahraee M, et al. (2020-04-01). "First-in-human, randomized dose-escalation study of the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of PF-06480605 in healthy subjects". British Journal of Clinical Pharmacology. 86 (4): 812–824. doi:10.1111/bcp.14187. ISSN 1365-2125. PMC 7098865. PMID 31758576.
- ^ a b c Hoffmann-La Roche (2025-06-05). A Phase III, Multicenter, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Induction Therapy With RO7790121 in Patients With Moderately to Severely Active Ulcerative Colitis (Report). clinicaltrials.gov.
- ^ a b c Hoffmann-La Roche (2025-06-04). A Phase III, Multicenter, Double-Blind, Placebo-Controlled, Treat-Through Study to Assess the Efficacy and Safety of Induction and Maintenance Therapy With RO7790121 in Patients With Moderately to Severely Active Ulcerative Colitis (Report). clinicaltrials.gov.
- ^ a b c d e f g h i j k "Afimkibart Clinical Naked monospecific - YAbS database". Antibody Society. 2025-06-11. Retrieved 2025-06-11.
- ^ a b Hoffmann-La Roche (2024-01-17). A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate The Efficacy, Safety, and Pharmacokinetics of PF-06480605 in Adult Participants With Moderate To Severe Ulcerative Colitis (Report). clinicaltrials.gov.
- ^ a b c d "What is the mechanism of action of Afimkibart?". PatSnap Synapse. Retrieved 2025-06-11.
- ^ Solitano V, Jairath V, Ungaro F, Peyrin-Biroulet L, Danese S (May 2024). "TL1A inhibition for inflammatory bowel disease treatment: From inflammation to fibrosis". review. Med (New York, N.Y.). 5 (5): 386–400. doi:10.1016/j.medj.2024.03.010. PMID 38574740.
- ^ a b c d "Roche Group development pipeline" (PDF). Roche Group. Retrieved 2025-06-11.
- ^ a b c d e Danese S (2021-06-16). "Anti-TL1A Antibody PF-06480605 Safety and Efficacy for Ulcerative Colitis: A Phase 2a Single-Arm Study". Clinical Gastroenterology and Hepatology : The Official Clinical Practice Journal of the American Gastroenterological Association. 19 (11): 2324–2332.e6. doi:10.1016/j.cgh.2021.06.011. PMID 34126262. Retrieved 2025-06-11.
- ^ a b "Roche to acquire Telavant Holdings, Inc". Roche. 2023-10-23. Retrieved 2025-06-11.
- ^ a b Hoffmann-La Roche (2025-03-24). A Phase 2, Multicenter, Double-blind, Two-arm Study of Subcutaneous RO7790121 for the Treatment of Subjects With Moderate to Severe Active Crohn's Disease (Report). clinicaltrials.gov.
- ^ a b c "Afimkibart - Roche". Springer (AdisInsight). Retrieved 2025-06-11.
- ^ Guy's and St Thomas' NHS Foundation Trust (2021-07-02). Study of the Golimumab Exposure-Response Relationship Using Serum Trough Levels (Report). clinicaltrials.gov.
- ^ a b "Japanese Phase 1 Study for Global Development of Anti-TL1A Antibody PF-06480605: A Randomized, Placebo-Controlled, Single-Ascending Dose Study". ResearchGate. Retrieved 2025-06-11.