apraglutide (FE 203799) / Asahi Kasei, Ironwood Pharma - LARVOL DELTA

Emerging novel therapies for steroid-refractory acute graft-versus-host disease: recent advances and future directions. (PubMed, Curr Opin Immunol) - "However, resistance and intolerance to ruxolitinib necessitate exploring novel and combination therapies such as apraglutide, neihulizumab, and other targeted agents, which have shown promising results in clinical trials. The future direction is to develop personalized treatment strategies that incorporate biomarkers and diverse therapeutic modalities. The aim is to enhance disease management, aiming for sustainable control and improved quality of life in patients facing the challenges of SR-aGVHD."

Journal • Review • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Transplantation

Long-Term Treatment With Once-Weekly Apraglutide Reduces Parenteral Support Volume and Increases Clinical Responder Rates in Patients With Short Bowel Syndrome and Intestinal Failure: The STARS Extend Trial (ACG 2025) - P2, P3 | "As of January 2025, 166 patients were analyzed (APRA/APRA, n=119; PBRO/APRA, n=47). BL demographics and disease characteristics were generally balanced across groups (Table 1). Reductions in weekly PS volume from BL were similar in both groups (-36.1% vs -39.1% at week 52 for APRA/APRA vs PBO/APRA), with small variations in urine volume, fluid intake and body weight (Table 2)."

Clinical • Gastrointestinal Disorder • Short Bowel Syndrome

APOB-48: A PROMISING BIOMARKER FOR RESPONSE TO APRAGLUTIDE IN SHORT BOWEL SYNDROME WITH INTESTINAL FAILURE AND COLON-IN-CONTINUITY (UEGW 2025) - No abstract available

Biomarker • Gastrointestinal Disorder • Short Bowel Syndrome • APOB

THE GLP-2 ANALOG APRAGLUTIDE IMPROVES COLONIC BARRIER FUNCTION IN PATIENTS WITH SHORT BOWEL SYNDROME AND CHRONIC INTESTINAL FAILURE (UEGW 2025) - No abstract available

Clinical • Gastrointestinal Disorder • Short Bowel Syndrome

Glucagon-Like Peptide Peptide-2 (GLP-2) Agonists for Patients With Short Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (ACG 2025) - "Our meta-analysis of six RCTs comprising 470 patients demonstrated that GLP-2 agonists significantly reduced PS volume from baseline compared to placebo (MD -251; 95% CI: -363- -139; I2 = 0%). Subgroup analyses confirmed consistent reductions in PS volume with Teduglutide and Glepaglutide, but not with Apraglutide (MD -93; 95% CI: -344 - 156). Furthermore, GLP-2 agonists nearly doubled the number of responders (defined as a ≥20% reduction in PS volume) compared to placebo (RR 1.97; 95% CI: 1.47, 2.64; I2 = 0%)."

Retrospective data • Review • Gastrointestinal Disorder • Short Bowel Syndrome

Apraglutide for Short Bowel Syndrome: A Systematic Review (ACG 2025) - "We identified four key clinical studies (total N=180), summarized below:In a phase II trial (n=8) in SBS by Eliasson et al, once weekly apraglutide significantly increased urine volume (marker of fluid absorption) vs placebo.Another study by Eliasson et al was an open-label metabolic balance study (n=8) that showed that four weeks of apraglutide significantly increased wet weight fluid absorption by 741 g/day, and energy absorption by 1095 kJ/day. Electrolyte (Na⁺, K⁺) absorption also rose. A 52-week open-label Phase II "metabolic balance" study by Verbiest et al in 9 adults with SBS showed that apraglutide yielded a mean 52% reduction in weekly PS volume at 52 weeks (−4702 mL/week)."

Review • Gastrointestinal Disorder • Short Bowel Syndrome

CHANGES IN THE MUCOSA-ASSOCIATED AND LUMINAL MICROBIOTA WITH THE NOVEL LONG-ACTING GLP-2 ANALOG APRAGLUTIDE IN SHORT BOWEL SYNDROME WITH INTESTINAL FAILURE AND COLON-IN-CONTINUITY (UEGW 2025) - No abstract available

Gastrointestinal Disorder • Short Bowel Syndrome

Long-Term Treatment With Once-Weekly Apraglutide Reduces Parenteral Support Dependency and Allows to Reach Enteral Autonomy in Some Patients With Short Bowel Syndrome and Intestinal Failure: The STARS Extend Trial (ACG 2025) - P3 | "As of January 2025, 166 pts were analyzed (APRA/APRA: 119; PBRO/APRA: 47). BL demographics and disease characteristics were generally balanced across groups. At week 52, ≥1 day/week off PS was achieved by 49.1% and 55.3% of APRA/APRA and PBO/APRA pts (Table 1), with small variations in urine volume, fluid intake and body weight (Table 2)."

Clinical • Gastrointestinal Disorder • Short Bowel Syndrome

Ironwood Pharmaceuticals Reports Second Quarter 2025 Results; Maintains Full Year 2025 Financial Guidance (Businesswire) - "Following discussions with the U.S. Food and Drug Administration ('FDA') in April 2025, the Company is finalizing a confirmatory apraglutide Phase 3 trial design for patients with SBS who are dependent on PS and plans to align with the FDA in the fourth quarter of 2025. Pending alignment with the FDA, Ironwood expects to initiate a confirmatory Phase 3 trial in the first half of 2026."

New P3 trial • Short Bowel Syndrome

Ironwood Pharmaceuticals Provides Clinical and Regulatory Update on Apraglutide (Businesswire) - "Ironwood Pharmaceuticals, Inc...announced that, based on a recent discussion with the U.S. Food and Drug Administration (FDA), a confirmatory Phase 3 trial is needed to seek approval of apraglutide for patients with short bowel syndrome (SBS) with intestinal failure (IF) who are dependent on parenteral support....In preparation for the new drug application (NDA) submission, pharmacokinetic analysis indicated that the exposure and dose delivered in the STARS Phase 3 trial were lower than planned due to dose preparation and administration. Based on the strength of the STARS Phase 3 results, Ironwood believed that there was a regulatory path forward. However, following recent dialogue with the FDA it became clear that a confirmatory Phase 3 trial is needed to seek approval. Ironwood plans to work with the FDA on the design of a confirmatory Phase 3 trial and the regulatory path forward."

FDA event • Short Bowel Syndrome

COMPARISONS OF GLUCAGON-LIKE PEPTIDE-2 ANALOG APRAGLUTIDE IN COMBINATION WITH RUXOLITINIB FOR STEROID-REFRACTORY GASTROINTESTINAL ACUTE GRAFT-VERSUS-HOST DISEASE WITH MAGIC CONTROL COHORT: THE PHASE 2 STARGAZE TRIAL (EBMT 2025) - P2 | "STARGAZE short- and long-term interim results compared favourably to a MAGIC control cohort. More patients with SR lower-GI aGvHD treated with ruxolitinib had response at day 28, more patients maintained their response over time, and fewer patients experienced day 180 NRM compared with ruxolitinib alone. These findings are encouraging but should be interpreted with caution, given that the control arm was constructed from observational data and the small sample size."

Combination therapy • P2 data • Acute Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Immunology

SAFETY AND EFFICACY OF THE GLUCAGON-LIKE PEPTIDE 2 ANALOG APRAGLUTIDE IN COMBINATION WITH RUXOLITINIB IN STEROID-REFRACTORY GASTROINTESTINAL ACUTE GRAFT-VERSUS-HOST DISEASE: THE PHASE 2 STARGAZE TRIAL (EBMT 2025) - P2 | "In STARGAZE, apraglutide was well tolerated and efficacious when added to ruxolitinib in the 2L setting. Most patients receiving apraglutide plus ruxolitinib had an overall response (all-organ and lower-GI) at days 28 and 56. Notably, durable ORs were observed from day 28 to 56 and from day 56 to 91."

Clinical • Combination therapy • P2 data • Acute Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Immunology

Apraglutide/Ruxolitinib Provides Efficacy Benefit vs Ruxolitinib Alone in Refractory GI aGVHD (OncLive) - P2 | N=31 | STARGAZE (NCT05415410) | Sponsor: VectivBio AG | "The selective GLP-2 analog apraglutide plus ruxolitinib (Jakafi) generated improved short- and long-term efficacy outcomes vs ruxolitinib alone in patients with steroid-refractory gastrointestinal (GI) acute graft-vs-host disease (aGVHD), according to findings from a study comparing efficacy outcomes from the phase 2 STARGAZE trial (NCT05415410) vs a control cohort from the observational MAGIC trial....The data, which were presented at the 51st Annual EBMT Meeting, showed that the all-organ overall response rates (ORRs) were higher in the STARGAZE cohort (n = 31; apraglutide vs ruxolitinib) vs the MAGIC cohort (n = 31; ruxolitinib monotherapy) at days 28 (STARGAZE, 58.1%; MAGIC, 38.8%), 56 (45.1%; 32.2%), and 91 (45.1%; 25.8%). The complete response (CR) rates at these respective time points were also higher in STARGAZE (25.8%; 29.0%; 29.0%) vs MAGIC (19.4%; 16.1%; 16.1%)."

P2 data • Acute Graft versus Host Disease

Ironwood Pharmaceuticals…Updates Corporate Structure to Position for the Future (Businesswire) - "Strategic Reorganization:...Ironwood also has decided to wind down the Phase 2 exploratory study, STARGAZE, of apraglutide in Graft-versus-Host Disease to further focus its resources and investments. Ironwood expects to incur restructuring charges of approximately $20 to $25 million, which are anticipated to be incurred primarily in the first half of 2025. Ironwood expects to realize, as a result of the strategic reorganization, approximately $55 to $60 million of annual operating expense savings, resulting in $40 to $45 million benefit to annual profits, net of impact to collaborative arrangements revenue."

Commercial • Trial termination • Acute Graft versus Host Disease

Ironwood Pharmaceuticals…Highlights Compelling New Data… (Businesswire) - P3 | N=158 | STARS extend (NCT05018286) | Sponsor: VectivBio AG | "Apraglutide Open Label Extension Study, STARS Extend: The extension study data demonstrate that more patients weaned off parenteral support with longer exposure to apraglutide. An analysis of long-term extension data also showed that 27 apraglutide-dosed patients achieved enteral autonomy, which is the ultimate goal of SBS patients who are dependent on parenteral support."

P3 data • Short Bowel Syndrome

Ironwood Pharmaceuticals Initiates Apraglutide NDA Submission… (Businesswire) - "...'We have made important progress by initiating our rolling new drug application ('NDA') submission and announcing new data from our open label extension study, STARS Extend, demonstrating an increased number of patients on apraglutide achieving enteral autonomy over time. We plan to include the long-term extension data in our NDA submission, in addition to the robust efficacy and tolerability data from STARS, the largest Phase 3 clinical trial ever conducted in SBS-IF patients'....Submission completion expected in Q3 2025."

FDA filing • Short Bowel Syndrome

The Phase 2 Stargaze Trial of the Glucagon-like Peptide 2 (GLP-2) Analog Apraglutide in Combination with Ruxolitinib for Steroid-Refractory Gastrointestinal (GI) Acute Graft-Versus-Host Disease (aGvHD): Comparisons with a MAGIC Control Cohort (TCT-ASTCT-CIBMTR 2025) - P2 | "More pts with SR lower-GI aGvHD treated with RUX + APRA had response at day 28, more pts maintained their response over time, and fewer pts experienced day 180 NRM compared with RUX alone. These findings are encouraging but should be interpreted with caution, given that the control arm was constructed from observational data and the small sample size."

Combination therapy • P2 data • Acute Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Immunology

STARGAZE: Proof-of-concept Trial of Apraglutide in GVHD (clinicaltrials.gov) - P2 | N=31 | Terminated | Sponsor: VectivBio AG | Trial completion date: Aug 2025 ➔ Dec 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2025 ➔ Dec 2024; Company decision

Trial completion date • Trial primary completion date • Trial termination • Acute Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Immunology

Safety and Efficacy of the Glucagon-like Peptide 2 (GLP-2) Analog Apraglutide in Patients with Steroid-Refractory Gastrointestinal Acute Graft-Versus-Host Disease (aGvHD) in Combination with Best Available Therapy: Results from a Multicenter, Randomized, Single-Blind, Proof-of-Concept, Phase 2 Stargaze Trial (ASH 2024) - P2 | "GI aGvHD is often steroid-refractory, and despite recent improvements with the availability of ruxolitinib (RUX) as second-line therapy, an unmet need remains for non-immunosuppressive treatments. Notably, durable overall responses were observed from Day 28 to Day 56 and from Day 56 to Day 91. The outcomes, based on the novel regenerative mechanism of action of APRA, are encouraging in this severely ill population."

Clinical • Combination therapy • P2 data • Acute Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Immunology

Use of glucagon-like polypeptide 2 analogs for intestinal failure. (PubMed, Expert Opin Pharmacother) - "More recently, ultralong acting GLP-2 analogs with half-lives of 70-80 hours can improve gastrointestinal function in surgically foreshortened bowel with only one injection every three to seven days. Future research is likely to focus upon the potential complementary role of GLP-1 and GLP-2 in treating short bowel syndrome."

Journal • Gastrointestinal Disorder • Pediatrics • Short Bowel Syndrome

The Long-Acting Glucagon-Like Peptide-2 Analog Apraglutide Enhances Intestinal Protection and Survival After Chemotherapy and Allogeneic Transplantation in Mice. (PubMed, Ann Transplant) - "CONCLUSIONS Apraglutide protects intestinal function and improves survival in mice following allogeneic transplantation or chemotherapy with cytarabine or melphalan. The potential effect of apraglutide on chemotherapy efficacy and on engraftment following allogeneic transplantation has been investigated in a parallel manuscript."

Journal • Preclinical • Fatigue • Gastrointestinal Disorder • Infectious Disease • Septic Shock • Transplantation

Safety, Tolerability, PK/PD of FE 203799 in Adults With Lymphomas (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: GlyPharma Therapeutics | Phase classification: P1b/2a ➔ P1/2

Phase classification • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD34

Safety and Tolerability of Once-Weekly Glucagon-Like Peptide-2 Analog Apraglutide in Patients With Short Bowel Syndrome and Intestinal Failure: Results From a Global, Phase 3, Randomized, Double-Blind Trial (ACG 2024) - P3 | "Incidence of AEs, serious AEs, and AEs of Grade ≥3 was similar between treatment arms ( Table 1 ). Dose interruptions due to AEs were also similar between APRA and PBO (10.9% vs 11.3%). The incidence of AEs associated with gastrointestinal (GI) tolerability was low and similar between treatment arms."

Clinical • P3 data • Cardiovascular • Gastrointestinal Disorder • Oncology • Short Bowel Syndrome

Phase 3, Double-Blind, Randomized STARS Trial of Apraglutide Once-Weekly in Patients with Short Bowel Syndrome and Intestinal Failure (SBS-IF): Subgroup Analyses by Baseline Demographics and SBS Disease Characteristics (ACG 2024) - P3 | "The primary endpoint was met at Wk 24 (n=163; overall population), with a significantly larger reduction in weekly PS volume from BL with APRA vs PBO (-25.5% vs -12.5%, p=0.001). These results have been presented previously. Subgroup analyses showed consistent treatment effect for APRA vs PBO across all subgroups in the overall population ( Figure 1 )."

Clinical • P3 data • Gastrointestinal Disorder • Short Bowel Syndrome

Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon-in-continuity: A multicenter, open-label, metabolic balance study. (PubMed, Clin Nutr) - P2 | "Apraglutide had an acceptable safety profile and was associated with significant reductions in PS needs and days off PS, improvements in intestinal absorption, and structural and functional intestinal changes in patients with SBS-IF-CiC."

Journal • Gastrointestinal Disorder • Short Bowel Syndrome