Treatment of ulcerative colitis, a chronic inflammatory bowel disease, with the new monoclonal antibody afimkibart led to remission of symptoms and signs of the disease in some patients affected by its moderate-to-severe form.

This is reported by a phase 2b multicenter clinical study, led by Professor Silvio Danese, Head of the Gastroenterology and Digestive Endoscopy Unit at IRCCS San Raffaele Hospital and Full Professor of Gastroenterology at Vita-Salute San Raffaele University, recently published in The Lancet Gastroenterology & Hepatology.

The Monoclonal Antibody afimkibart: What is it and how does it work?

Afimkibart is a drug that works by sequestering TL1A, a molecule that promotes inflammation and fibrosis, both key features of ulcerative colitis.

Once sequestered, TL1A can no longer bind to its receptor found on immune cells and fibroblasts and therefore cannot trigger the cascade of cellular events that lead to inflammation and fibrosis.

As a result, afimkibart attenuates the inflammatory and fibrotic response that characterizes ulcerative colitis.

The TUSCANY-2 Multicenter Study Results

The TUSCANY-2 clinical trial, involving 114 centers across 23 countries and led by San Raffaele Hospital, tested the safety and efficacy of afimkibart in treating moderate to severe ulcerative colitis.

Three different doses (50 mg, 150 mg, and 450 mg) of the drug were evaluated, administered subcutaneously every four weeks over a total period of 52 weeks. Alongside each group of patients receiving a specific dose, a control group received a placebo.

All patients underwent colonoscopy at 14 and 56 weeks from the start of treatment to assess disease progression and intestinal wall characteristics.
In all patients who received afimkibart, the drug showed an acceptable safety profile and did not cause significant side effects.

Regardless of the administered dose, afimkibart also led to a clinically relevant remission of disease symptoms and signs in a subset of the treated patients, compared to those who received the placebo.

The drug demonstrated effectiveness as early as 14 weeks after the first dose, and this efficacy was maintained for up to 56 weeks, regardless of the dosage.

Overall, the results of the TUSCANY-2 trial identify afimkibart as a promising alternative for treating moderate-to-severe ulcerative colitis.

Future Perspectives

Ulcerative colitis is a chronic inflammatory diseases affecting the mucosal layer (inner lining) of the intestinal wall. While several therapeutic options exist—including immunosuppressive drugs, JAK inhibitors, and biologics such as monoclonal antibodies—many patients do not respond or only partially respond to currently available treatments.

“It is therefore crucial to continue researching new therapeutic targets and strategies that can mitigate the inflammation and fibrosis associated with moderate and severe forms of ulcerative colitis,” says Professor Silvio Danese, lead author of the TUSCANY-2 study. “This is the largest phase 2b multicenter trial conducted on a new class of drugs targeting TL1A as afimkibart does. Phase 3 clinical trials are currently underway to confirm the efficacy of these drugs in treating both ulcerative colitis and Crohn’s disease, another chronic inflammatory bowel condition,” concludes the Professor.