Gilead’s investigational oral α4β7 inhibitor emvistegrast met the Phase 2 primary endpoint in ulcerative colitis, with improvements in remission and endoscopic outcomes.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Gilead Sciences announced positive Phase 2 SWIFT results on 19 October 2026, evaluating emvistegrast (GS-1427), an investigational once-daily oral α4β7 integrin inhibitor, in adults with moderately to severely active ulcerative colitis (UC). The 12-week placebo-controlled induction results were presented at United European Gastroenterology Week (UEGW) 2026 in Barcelona, Spain.
At Week 12, clinical response, the primary endpoint based on the modified Mayo clinical score, was achieved by 66% of participants receiving emvistegrast 200 mg, compared with 37% receiving placebo (nominal p<0.001). Clinical remission occurred in 31% versus 8%, respectively (nominal p<0.05).
The difference between response and remission rates is clinically relevant. Although more participants experienced an improvement in disease activity, fewer achieved remission. These findings suggest a meaningful short-term efficacy signal, but the results do not establish sustained disease control or superiority over existing treatments.
Endoscopic and Histological Outcomes Extend the Efficacy Signal
Secondary endpoints also favoured emvistegrast 200 mg at Week 12. Histological endoscopic mucosal improvement (HEMI) was achieved by 25% of participants receiving emvistegrast, compared with 10% receiving placebo (nominal p<0.05). Mucosal healing occurred in 24% versus 10%, respectively (nominal p<0.05), while endoscopic improvement was reported in 39% versus 12% (nominal p<0.001).
These findings extend the efficacy signal beyond clinical response to measures of intestinal inflammation and mucosal disease activity. However, the reported p-values are nominal and should be interpreted cautiously because multiple endpoints were assessed. The available announcement also does not provide the complete efficacy results for the 25 mg and 75 mg groups, limiting assessment of the dose-response relationship.
Safety Profile and Study Population
Adverse events occurred in 64 of 178 participants (36%) receiving emvistegrast across all three dose groups and 22 of 60 participants (37%) receiving placebo. Events were largely Grade 2 or lower. Serious adverse events occurred in four participants (2%) across the emvistegrast groups, compared with none receiving placebo. All four serious events were considered unrelated to study treatment. Three of 238 participants (1%) discontinued because of adverse events.
These findings provide an initial assessment of short-term tolerability. However, the 12-week induction period is insufficient to characterize long-term safety.
Approximately 78% of participants were naïve to advanced therapies or had not failed an advanced therapy for UC, while 22% had previously failed one or two advanced therapies. The study excluded participants previously exposed to vedolizumab or other integrin antagonists. Consequently, the results do not establish efficacy in patients previously treated with an α4β7 integrin inhibitor or in more heavily pretreated populations.
SWIFT (NCT06290934) is a randomized, double-blind, placebo-controlled, multicentre, dose-ranging Phase 2 study enrolling adults aged 18–75 years with moderately to severely active UC. Eligibility required a modified Mayo Clinic Score of 5–9 and a centrally read endoscopic subscore of at least 2. Participants were randomized to once-daily oral emvistegrast 200 mg, 75 mg or 25 mg, or placebo. The study includes a 12-week induction phase, blinded maintenance through Week 52 and a treatment extension through Week 116.
Gilead plans to initiate a Phase 3 monotherapy study in 2027 and is considering emvistegrast as a potential backbone for future combination approaches.
Clinical Interpretation
SWIFT provides an encouraging early efficacy signal for oral α4β7 inhibition in UC, with the 200 mg dose outperforming placebo across clinical response, remission and several endoscopic or histological measures. Similar overall adverse-event rates offer preliminary reassurance regarding short-term tolerability.
Nevertheless, the findings remain limited to the induction phase, and nominal p-values across multiple endpoints warrant cautious interpretation. The predominance of participants without prior advanced-therapy failure also limits conclusions about efficacy in treatment-refractory disease. Maintenance results, longer-term safety follow-up and Phase 3 confirmation will be needed to determine whether the benefits are durable and clinically meaningful. Although once-daily oral administration offers a different treatment route, convenience alone does not establish an advantage over existing therapies.
Emvistegrast remains investigational and has not been approved globally; its safety and efficacy have not been established.
Reference
Phase 2 SWIFT Study of Emvistegrast, a Potential Differentiated Once-daily Oral Treatment, Meets Primary Endpoint in Ulcerative Colitis, Gilead Science, October 19 2026
Study of GS-1427 in Participants with Moderately to Severely Active Ulcerative Colitis (SWIFT), ClinicalTrials.gov ID NCT06290934
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.