Ironwood spies new frontier for $1B GLP-2 analog in exploratory phase 2 rare disease trial

Ironwood Pharmaceuticals’ stargazing has identified a new frontier for apraglutide by generating early clinical evidence that the GLP-2 analog plays nicely with Incyte’s Jakafi in a rare disease. The company acquired the molecule last year through its $1 billion takeover of VectaBio. 

The exploratory phase 2 STARGAZE trial is testing three doses of the long-acting GLP-2 analog apraglutide in 31 people with steroid-refractory gastrointestinal acute graft-versus-host disease (SR GI aGVHD). The GI tract is one of the main tissue systems damaged by aGVHD, and Ironwood sees an ongoing need for non-immunosuppressive treatment options.

Subjects received the investigational molecule on top of standard-of-care therapies including ruxolitinib, which Incyte sells as Jakafi, and systemic corticosteroids. Ironwood said “the majority of patients responded to treatment by Day 28 and Day 56.” All the lower gastrointestinal responses seen at Day 28 persisted through to Day 91. Safety and tolerability were in line with expectations for the use of standard of care and a GLP-2 analog in GVHD patients.

Robert Zeiser, M.D., professor of hematology and oncology at the University of Freiburg in Germany and principal investigator for the STARGAZE study, called the data “an important step forward for patients with SR GI aGVHD given limited duration of response with currently approved agents.”   

“Given its potential GI effect on tissue regeneration and function, apraglutide may have a role in the advanced management of acute GI GVHD through a non-immunosuppressive approach,” Zeiser added.

Ironwood will keep tracking participants and reevaluate the safety and efficacy of apraglutide after two years. As well as continuing to track safety and GI responses, researchers are looking at the effect of the molecule on outcomes including graft failure and overall survival out to two years after the start of treatment. 

Investors were unmoved by the update, remaining in the funk that began when Ironwood shared phase 3 data on apraglutide one month ago. That study linked apraglutide to improvements in short bowel syndrome (SBS), but investors wanted more and promptly wiped 30% off Ironwood’s share price. The company plans to file for approval in SBS using the data.