GVHD Treatments Pegtarazimod and Belumosudil Make International Inroads

Two promising treatments for patients with graft-versus-host-disease (GVHD), pegtarazimod (RLS-0071) and belumosudil (Rezurock), made significant progress on global regulatory pathways.

Pegtarazimod received an orphan drug designation for GVHD from the European Medicines Agency (EMA).¹ The designation is intended to expedite the development and review of treatments for rare diseases and conditions. Belumosudil was approved in Thailand for the treatment of patients with GVHD.²

Pegtarazimod

Pegtarazimod is a 15-amino-acid peptide that targets humoral and cellular inflammation.¹ The EMA granted the orphan drug designation to the novel therapy based on early data from the ongoing, open-label, prospective, dose-escalation phase 2 AURORA trial (NCT06343792). The study is exploring pegtarazimod in patients who are hospitalized with steroid-refractory acute GVHD. Researchers are aiming to enroll between 60 and 70 patients at clinical locations in the United States, Germany, and Spain.

The trial is enrolling male and female patients who are at least 12 years old who have been hospitalized with steroid-refractory grade II to IV acute GVHD following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients cannot enroll if they have received more than 1 allo-HSCT, have received or intend to receive systemic therapy beyond ruxolitinib or corticosteroids for acute GVHD, or have previously had treatment failure on ruxolitinib.³

All patients enrolled in the trial will be treated with pegtarazimod for 7 or 14 days according to their assigned dose group.

The primary end points of the study are overall response rate over day 1 to 28 following treatment and treatment-related adverse events/treatment-emergent serious adverse events over the first 180 days after treatment. Data from the trial are next expected to report in 2026, according to ReAlta, the company developing pegtarazimod.¹

Pegtarazimod was granted orphan drug designation from the FDA in 2024.⁴

“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. 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,” Kenji Cunnion, MD, MPH, chief medical officer, ReAlta, stated in a press release.¹

Belumosudil

The Ministry of Public Health in Thailand approved the ROCK2 inhibitor belumosudil for the treatment of adult and pediatric patients 12 years and older with chronic GVHD after failure of at least 2 prior lines of systemic therapy.²

Belumosudil was approved by the FDA the same indication in July 2021.⁵ The efficacy of the drug was established in the multicenter, randomized, dose-ranging, open-label KD025-213 trial (NCT03640481). The study population comprised 65 patients with chronic GVHD who received oral belumosudil at 200 mg once daily.

The overall response rate in the trial was 75%, including a complete response rate of 6% and a partial response rate of 69%. The median time to response and duration of response were 1.8 months and 1.9 months, respectively. Among responders, 62% of patients were alive and did not start a new systemic therapy for at least 12 months following their response.

Adverse events occurring in at least 20% of patients in the trial included laboratory abnormalities, were infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma glutamyl transferase increased, lymphocytes decreased, and hypertension.

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 28, 2025. https://tinyurl.com/3bkvynm9

2. REZUROCK®, a Selective ROCK2 Inhibitor, Approved in Thailand for Chronic GVHD Treatment. Posted August 22, 2025. Access August 28, 2025. https://www.meiji.com/global/news/2025/pdf/250822_01.pdf

3. 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 28, 2025. https://www.clinicaltrials.gov/study/NCT06343792

4. 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 28, 2025. https://tinyurl.com/y2b4xc8h

5. FDA approves belumosudil for chronic graft-versus-host disease. Posted July 16, 2021. Accessed August 28, 2025. https://tinyurl.com/ycxp6r9v