EMA Grants Orphan Drug Designation to Pegtarazimod for GVHD

The European Medicines Agency (EMA) has granted orphan drug designation (ODD) to pegtarazimod (RLS-0071) for the treatment of patients with graft-vs-host disease (GVHD).¹

The EMA designation was based on data from an ongoing phase 2 AURORA trial (NCT06343792), which is evaluating pegtarazimod in 6 experimental and 2 expansion cohorts of hospitalized patients with steroid-refractory acute GVHD.^1,2

“Receiving EMA orphan drug designation represents a significant new regulatory milestone in our efforts to address the urgent unmet need in acute GVHD, and we are particularly encouraged by the EMA’s positive feedback to our initial cohort of phase 2 data,” David Marek, chief executive officer of ReAlta, stated in a news release.¹ “This designation, alongside our existing FDA orphan drug and fast track designations for acute GVHD, validates the potential of our novel dual-targeting approach to modulate both neutrophil and complement-mediated inflammation as we advance our phase 2 trial to bring this potential therapy to acute GVHD patients in Europe.”

In August 2024, the FDA granted ODD and fast track designation to pegtarazimod in the same indication.³

Pegtarazimod is a 15-amino-acid peptide that targets humoral and cellular inflammation through selective inhibition of complement activation at C1, myeloperoxidase activity, and neutrophil extracellular trap formation.¹ Findings from a study (NCT05351671) published in 2024 illustrated the agent’s mechanism, showcasing reduced neutrophils in sputum 6 hours after healthy participants inhaled low-dose lipopolysaccharide by approximately half compared with placebo (P = .04). Neutrophil effectors myeloperoxidase, neutrophil elastase and IL-1β in sputum were also significantly reduced at the same point vs placebo.⁴

Through direct inhibition of these mechanisms, pegtarazimod prevents the inflammatory cascade and tissue damage that results from donor immune cells attacking recipient tissues after hematopoietic stem cell transplantation (HSCT).¹

AURORA is an ongoing phase 2 open-label, prospective, dose-escalation trial that is enrolling patients globally in the United States, Germany, and Spain.

Eligible patients include adults or adolescents over the age of 12 years who are hospitalized for the treatment of steroid-refractory acute, grade II to IV GVHD after allogeneic HSCT.²

Patients must have an expected hospital length-of-stay of at least 1 week from the time of RLS-0071 initiation and weigh between 40 kg and 140 kg at screening.Additionally, patients can not plan to undergo additional GVHD treatment or to add, dose-adjust, or discontinue prophylactic GVHD medications during the 7-day treatment course of RLS-0071 pegtarazimod.

Additional enrollment parameters include neutrophil recovery following transplant, defined as a blood neutrophil count above 500/mL without growth factor supplementation for at least 3 consecutive measurements.

Eligible patients will receive pegtarazimod for 7 or 14 days according to the assigned dose group. Cohorts 1 through 5 will receive the agent at a dose of either 10 mg/kg every 8 hours (Q8H) for 7 days, 40 mg/kg Q8H for 7 days, 10 mg/kg Q8H for 14 days with concurrent ruxolitinib, 40 mg/kg Q8H for 14 days with concurrent ruxolitinib, 10 mg/kg Q8H for 7 days followed by 10 mg/kg daily for 7 days with concurrent ruxolitinib, or 40 mg/kg Q8H for 7 days followed by 40 mg/kg daily for 7 days with concurrent ruxolitinib.

In dose expansion patients will receive 10 mg/kg or 40 mg/kg of RLS-0071 Q8H for 7 or 14 days.

The primary end points are the number of patients with treatment-related adverse effects and treatment-emergent serious adverse effects in addition to overall response rate. Secondary end points include the incidence of refractoriness to RLS-0071 with or without ruxolitinib (Jakafi), overall corticosteroid use, overall survival, non-relapse mortality, and duration of hospital stay. Investigators will also evaluate the change or shift in overall grade of acute GVHD, the change or shift in stage for acute lower gastrointestinal (GI), liver, skin, or upper GI GVHD from baseline according to MAGIC criteria, the initiation of additional or alternative treatments for acute GVHD, and achievement of stage 0 or 1 acute lower GI, liver, skin, or upper GI GVHD.

“Our targeted intervention addresses the specific pathways driving tissue damage, including the inhibition of extracellular myeloperoxidase, NETosis and neutrophil elastase, while preserving beneficial immune function, unlike broadly immunosuppressive approaches to treat acute GVHD,” Kenji Cunnion, MD, MPH, chief medical officer of ReAlta, stated in a news release.¹ “The compelling preclinical and clinical data that we have generated shows pegtarazimod’s potential to address the neutrophil-driven disease process in patients with lower gastrointestinal acute GVHD that is the most difficult to treat and has the highest rate of mortality.”

Data from additional cohorts of the phase 2 trial are expected in 2026.

References

1. ReAlta Life Sciences receives EMA orphan drug designation for RLS-0071 (pegtarazimod) for the treatment of graft-versus-host disease. News release. ReAlta Life Sciences. August 21, 2025. Accessed August 22, 2025. https://realtalifesciences.com/news/realta-receives-ema-orphan-drug-designation-for-rls-0071-pegtarazimod-for-the-treatment-of-graft-versus-host-disease/
2. Safety, PK, PD, dosing, and efficacy of RLS-0071 for the treatment of hospitalized patients with steroid-refractory acute graft-versus-host disease (AURORA). ClinicalTrials.gov. Updated January 31, 2025. Accessed August 22, 2025. https://www.clinicaltrials.gov/study/NCT06343792
3. ReAlta granted FDA orphan drug designation and fast track designation for RLS-0071 for the treatment of steroid-refractory acute graft-versus-host disease. News release. ReAlta Life Sciences. August 19, 2024. Accessed August 22, 2025. https://realtalifesciences.com/news/realta-granted-fda-orphan-drug-designation-and-fast-track-designation-for-rls-0071-for-the-treatment-of-steroid-refractory-acute-graft-versus-host-disease/
4. Cunnion K, Goss J, Hair P, et al. RLS-0071, a novel anti-inflammatory agent, significantly reduced inflammatory biomarkers in a randomised human evaluation of mechanisms and safety study. ERJ Open Res. 2024;10(4):01006-2023. doi:10.1183/23120541.01006-2023