ReAlta Reports Promising Phase 2 Results for Pegtarazimod in Steroid-Refractory Acute Graft-Versus-Host Disease
Key Insights
ReAlta Life Sciences (search) presented interim Phase 2 data showing pegtarazimod achieved clinical improvement in all 6 patients with steroid-refractory acute graft-versus-host disease at ASH 2025.
The treatment demonstrated a statistically significant 68% reduction in plasma myeloperoxidase (search) levels (p = 0.02), indicating modulation of neutrophil-driven inflammatory mechanisms.
Four of five patients showed lower gastrointestinal MAGIC stage improvement of 1-3 stages over 7 days of treatment with no dose-limiting toxicities.
ReAlta Life Sciences (search) reported encouraging interim Phase 2 clinical data for pegtarazimod (RLS-0071) in patients with steroid-refractory acute graft-versus-host disease (aGvHD) at the 67th American Society of Hematology Annual Meeting. The open-label, prospective, dose-escalation study demonstrated clinical improvement across all six patients in the treatment optimization cohort, with particularly notable responses in lower gastrointestinal manifestations.
Clinical Efficacy and Biomarker Results
The study evaluated pegtarazimod at 10mg/kg administered with ruxolitinib for 7 days in hospitalized patients with steroid-refractory aGvHD. Clinical MAGIC Stage improvement was observed for all 6 patients, with 4 of 5 participants demonstrating lower gastrointestinal MAGIC Stage improvement of 1, 2, or 3 stages over the treatment period.
A key pharmacodynamic finding showed median plasma myeloperoxidase (search) (MPO) levels decreased by 68% (p = 0.02), suggesting modulation of neutrophil-driven inflammatory mechanisms. This statistically significant reduction in MPO levels indicates the drug's ability to engage its intended target and potentially reduce tissue damage associated with the condition.
Safety Profile and Treatment Approach
The safety profile was characterized by no dose-limiting toxicities or serious adverse events attributed to the study drug. Preliminary efficacy was evaluated by clinical response in the lower gastrointestinal tract, skin and liver, characterized as Grade II, III or IV per Mount Sinai Acute GVHD International Consortium (MAGIC) guidelines.
"Pegtarazimod treatment shows compelling clinical improvements for patients with steroid-refractory aGvHD, particularly in lower gastrointestinal involvement," said Robert Zeiser, M.D., from the Medical Center, University of Freiburg and lead author of the study. "The statistically significant decrease in plasma myeloperoxidase (search) levels suggests a direct pathway to reducing tissue damage and potentially improving outcomes for patients with this life-threatening condition."
Mechanism of Action and Development Strategy
Pegtarazimod represents what ReAlta describes as a "pipeline-in-a-product" approach, inhibiting C1 and MBL activation within the classical and lectin pathways to block inflammatory cascade initiation while simultaneously blocking myeloperoxidase (search) to prevent activation of toxic reactive oxidative species and formation of neutrophil extracellular traps that accelerate tissue damage.
Kenji Cunnion, M.D., Chief Medical Officer of ReAlta, explained: "This data demonstrates pegtarazimod's unique ability to target multiple inflammatory pathways simultaneously, particularly in lower gastrointestinal aGvHD, a condition with historically poor patient outcomes. By selectively inhibiting complement (search) activation and neutrophil-driven mechanisms, we are exploring a novel therapeutic approach that could transform the clinical management of this complex and life-threatening disease."
Regulatory Status and Broader Development Program
ReAlta has secured multiple FDA Orphan Drug and Fast Track Designations for pegtarazimod in hypoxic ischemic encephalopathy and aGvHD, along with European Medicines Agency Orphan Drug Designations for both indications. The company is currently advancing pegtarazimod through multiple Phase 2 clinical trials, including ongoing studies in newborns with moderate to severe hypoxic ischemic encephalopathy and a recently completed Phase 2 proof-of-concept study in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease.