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Afimkibart
Monoclonal antibody for inflammatory diseases From Wikipedia, the free encyclopedia
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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.[8][1]
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Mechanism of action
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]
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Development history
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]
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Clinical trials
Summarize
Perspective
Afimkibart is undergoing clinical trials for multiple indications, with significant progress in ulcerative colitis, Crohn’s disease, and atopic dermatitis.[4]
Ulcerative colitis
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
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
Afimkibart is in Phase II development for atopic dermatitis, with trials assessing subcutaneous administration in patients with moderate-to-severe disease.[12][4]
Pharmacokinetics
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]
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Adverse effects
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
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]
References
External links
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