Takeda Presents Positive Results from Phase 3 Study of Vedolizumab for Prevention of Intestinal Acute Graft-Versus-Host Disease (aGvHD) in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

Takeda has announced late-breaking data from the Phase 3 GRAPHITE study presented at the 2023 Tandem Meetings, demonstrating vedolizumab achieved a statistically significant and clinically meaningful improvement in lower gastrointestinal (GI) aGvHD-free survival by Day 180 after allo-HSCT with no relevant differences in safety profile versus placebo. Intestinal aGvHD is a serious complication characterized by inflammation of the GI tract which can affect patients undergoing allo-HSCT, a common treatment for blood cancers.

“Lower GI aGvHD represents a critical unmet need in patients undergoing allo-HSCT,” said Yi-Bin Chen, MD, Director, Hematopoietic Cell Transplant & Cell Therapy Program, Mass General Cancer Center. “I’m excited that this study can contribute to the understanding of this common and life-threatening complication in stem cell transplantation.”

Vedolizumab is not currently indicated for use in aGvHD.

The Phase 3, randomized, double-blind, placebo-controlled, multicenter GRAPHITE study evaluated the efficacy and safety of vedolizumab as prophylaxis for intestinal aGvHD in patients undergoing allo-HSCT from unrelated donors for the treatment of hematological malignancies. The study met its primary endpoint, with vedolizumab achieving a statistically significant improvement in intestinal aGvHD-free survival versus placebo by Day 180 after allo-HSCT (85.5% of patients in the vedolizumab arm versus 70.9% in the placebo arm [HR=0.45; 95% CI: 0.27, 0.73; p<0.001]).1 Statistically significant superiority of vedolizumab over placebo was also demonstrated for intestinal aGvHD-free and relapse-free survival by Day +180 (HR= 0.56, 95% CI: 0.37, 0.86; p = 0.0043), and for Grade C-D aGvHD-free (with any organ involvement) survival at Day +180 (HR: 0.59, 95% CI: 0.39, 0.91; p = 0.0204).1 In addition, no relevant differences in safety profile between the vedolizumab and placebo arms were observed, and no new safety signals were identified. Treatment-related adverse events were reported in 24.8% versus 28.4%, and treatment related serious adverse events in 8.5% versus 6.5% of patients treated with placebo versus vedolizumab, respectively. The most common adverse events of special interest were hypersensitivity reactions (placebo 82.4%, vedolizumab 79.3%), serious infections (placebo 67.3%, vedolizumab 74.0%), and liver injury (placebo 41.8%, vedolizumab 40.2%).1

“These results have advanced our understanding of vedolizumab, currently indicated for IBD, in another critical GI inflammatory condition,” said Chinwe Ukomadu, M.D., Ph.D., Head, Gastroenterology Therapeutic Area Unit at Takeda. “Our Phase 3 study in the prevention of lower GI aGvHD is the latest example of Takeda’s commitment to advancing the science of vedolizumab, furthering the understanding of its mechanism of action, and exploring new ways to help patients.”

Intestinal aGvHD can occur after stem cell transplantation when the immune cells of the donor (the graft) consider the recipient’s body (the host) as foreign and attack the organs and tissue.2 Intestinal aGvHD results in the majority of morbidity and mortality associated with GvHD. Effective prevention of aGvHD, especially with lower intestinal involvement, has been an important treatment goal for physicians when patients are undergoing allo-HSCT.