Gilead Sciences has notched a phase 2 win in ulcerative colitis (UC), with its once-daily pill emvistegrast outperforming placebo on the study's primary endpoint and setting the stage for a late-stage trial in 2027.
At week 12, 66% of patients receiving the 200-mg dose of emvistegrast achieved a clinical response, compared with 37% of placebo recipients, according to an Oct. 19 release. Clinical remission was achieved by 31% of patients in the treatment group, versus 8% in the placebo group.
The results came from the ongoing phase 2 Swift trial, which enrolled 238 adults with moderately to severely active UC. The randomized, placebo-controlled study evaluated three doses of emvistegrast: 25 mg, 75 mg and 200 mg. The findings were presented at United European Gastroenterology Week 2026 in Barcelona, Spain.
Emvistegrast is an oral inhibitor of α4β7 integrin, a protein found on certain immune cells that helps direct them to the gut. By blocking this pathway, the drug is designed to prevent immune cells from migrating into intestinal tissue, where they can contribute to the chronic inflammation associated with UC.
The 200-mg dose also delivered improvements across several secondary endpoints. At week 12, 25% of patients achieved histological endoscopic mucosal improvement, a measure that combines improvements in the intestinal lining observed during endoscopy with reductions in inflammation seen in tissue samples. That compared with 10% of placebo recipients.
Gilead also reported endoscopic improvement in 39% of patients receiving the 200-mg dose, compared with 12% of those on placebo.
The drug was generally well tolerated, with mostly grade 2 or lower adverse events reported in 36% of patients across the three emvistegrast dose groups, compared with 37% of placebo recipients. Serious adverse events occurred in 2% of emvistegrast recipients, although none were considered related to the treatment. Just 1% of all trial participants discontinued because of adverse events.
There are still questions to answer about the drug's durability and performance in harder-to-treat patients. Gilead reported that 78% of participants were either new to advanced therapies or had not previously experienced treatment failure with one, while 22% had failed one or two advanced therapies. The Swift trial remains ongoing, with additional maintenance data expected to shed light on whether the benefits observed at week 12 can be sustained.
"We plan to initiate a Phase 3 monotherapy study in 2027 and see emvistegrast as a potential backbone for future combination approaches,” Swati Tole, M.D., senior vice president of clinical development for inflammation at Gilead, said in the release.
Emvistegrast could eventually challenge Takeda's blockbuster Entyvio, an antibody that targets the same α4β7 integrin pathway. While Entyvio is administered intravenously or through subcutaneous injection, Gilead's candidate offers the potential convenience of a once-daily pill.
That distinction could give emvistegrast an advantage in a competitive treatment landscape, although its efficacy and safety will need to be established in larger trials before comparisons with approved therapies can be drawn.
Analysts at Evercore ISI believe the results represent “the strongest datasets ever for a monotherapy in UC,” suggesting that Gilead is “sitting on a foundational asset in UC.”
The UC market is already crowded with drugs targeting several inflammatory pathways. AbbVie's Skyrizi and Johnson & Johnson's Tremfya target IL-23, while AbbVie's Rinvoq is an oral JAK inhibitor.
Competition is also building among investigational therapies. Spyre Therapeutics recently reported a phase 2 win for SPY003, its half-life-extended antibody targeting IL-23. The biotech is also developing SPY001, an extended half-life antibody targeting the same α4β7 integrin pathway as emvistegrast, as part of a broader strategy to evaluate combination treatments.
Meanwhile, Merck & Co. reported positive phase 3 results in June for its anti-TL1A antibody tulisokibart, which the pharma acquired through its $11 billion purchase of Prometheus Biosciences in 2023.
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