Positive Phase II STARGAZE Trial Outcomes for Apraglutide in SR GI aGVHD Patients

A recent study has shed light on the potential of apraglutide, a glucagon-like peptide-2 (GLP-2) analog, in treating patients with steroid-refractory gastrointestinal acute Graft-versus-Host Disease (SR GI aGVHD). The Phase II exploratory STARGAZE trial, conducted by Ironwood Pharmaceuticals, Inc., has reported positive primary results up to Day 91, indicating that apraglutide is well-tolerated and has an acceptable safety profile when combined with standard care, which includes systemic corticosteroids and ruxolitinib.

The trial represents a pioneering effort in combining a GLP-2 analog with immunosuppressive therapy for SR GI aGVHD patients. The safety and tolerability of once-weekly apraglutide align with the known safety profile of GLP-2 analogs and the standard of care, as monitored by an independent safety review committee. This committee supported the continuation of the study without any modifications.

Secondary efficacy data from the trial revealed that patients treated with apraglutide and standard care exhibited lower gastrointestinal tract responses, which were sustained through Day 91. The majority of these patients showed a response to the treatment by Day 28 and Day 56, with all lower GI responders at Day 28 maintaining their response up to Days 56 and 91, based on available organ staging assessments.

Dr. Robert Zeiser, Principal Investigator for the STARGAZE study, highlighted the significance of these findings, especially considering the limited duration of response with currently approved agents for SR GI aGVHD. He suggested that apraglutide, with its potential to promote gastrointestinal tissue regeneration and function, could play a role in the advanced management of acute GI GVHD through a non-immunosuppressive approach.

Acute Graft-Versus-Host Disease (aGVHD) is a life-threatening condition that arises when donor immune cells attack the recipient's healthy cells post allogeneic hematopoietic stem cell transplant (HSCT). GI aGVHD, which affects the gastrointestinal tract, is a major cause of morbidity and mortality following HSCT, with approximately 70% of aGVHD cases involving the GI tract. Despite existing treatment options, many patients do not respond to first-line therapies such as corticosteroids, and even with second-line therapy, sustained response over time is not guaranteed, leading to significant non-relapse mortality after six months.

Michael Shetzline, Senior Vice President, Chief Medical Officer, and Head of Research and Development at Ironwood Pharmaceuticals, emphasized the importance of the STARGAZE trial's results in contributing to the understanding of apraglutide's safety and tolerability profile. He also noted the potential of GLP-2 in promoting intestinal healing and regeneration, which could be crucial for patients suffering from high morbidity and mortality rates due to SR GI aGVHD.

The STARGAZE trial is ongoing, with a two-year endpoint planned to further evaluate the safety and efficacy of apraglutide. Additional data from the trial is expected to be presented at a forthcoming medical congress. Ironwood Pharmaceuticals, a leading global GI healthcare company, is committed to advancing the treatment of GI diseases and redefining the standard of care for GI patients, with apraglutide being one of their key investigational compounds for rare gastrointestinal diseases.