GVHD treatments Pegtarazimod and Besudil make international progress

Two promising treatments for patients with graft-versus-host disease (GVHD), pegtarazimod (RLS-0071) andBelumosudil-Rezurock, have made significant advances in global regulatory pathways. Pegtarazimod received GVHD orphan drug designation from the European Medicines Agency (EMA). This designation is intended to expedite the development and review of treatments for rare diseases and conditions. Besudil is approved in Thailand to treat patients with graft-versus-host disease.

1. Pegtarazimod

Pegtarazimod is a 15-amino acid peptide that targets humoral and cellular inflammation. 1 Based on early data from the ongoing open-label, prospective, dose-escalating Phase 2 trial of AURORA (NCT06343792), the EMA granted orphan drug designation to this novel therapy. The study is exploring the use of pegtarazimod in hospitalized patients with steroid-refractory acute graft-versus-host disease. Researchers aim to enroll 60 to 70 patients at clinical sites in the United States, Germany and Spain.

The trial enrolled male and female patients at least12 years of age who were hospitalized with steroid-refractory grade II to IV acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients cannot be registered if they have received more than 1 allogeneic hematopoietic stem cell transplant, have received or plan to receive systemic therapy other than ruxolitinib or corticosteroids for acute graft-versus-host disease, or have previously failed ruxolitinib therapy.

All patients participating in the trial will receive Pegtarazimod for 7 or 14 days, depending on their assigned dose group. The study's primary endpoints were overall response rate from days 1 to 28 after treatment and treatment-related adverse events/treatment-emergent serious adverse events in the first 180 days after treatment.

Pegtarazimod was granted orphan drug designation by the U.S. Food and Drug Administration in April 2024. Our targeted intervention addresses specific pathways driving tissue damage, including inhibition of extracellular myeloperoxidase, NETosis, and neutrophil elastase, while preserving beneficial immune function, unlike broad immunosuppressive approaches to treat acute GVHD. The resulting preclinical and clinical data suggest that pegtarazimod has the potential to address the neutrophil-driven disease process in patients with acute GVHD of the lower gastrointestinal tract, which is the most difficult to treat and has the highest mortality rate.

2. Besudil mesylate tablets

The Ministry of Public Health of Thailand approved the ROCK2 inhibitor besudil for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease after at least 2 previous lines of systemic therapy have failed. In July 2021, the U.S. Food and Drug Administration approved besudil for the same indication. The drug's efficacy was established in the multicenter, randomized, dose-ranging, open-label KD025-213 trial (NCT03640481). The study population included 65 patients with chronic graft-versus-host disease who took 200 mg of besudil orally daily.

The overall response rate of the trial was 75%, with 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% remain alive and have not started new systemic therapy for at least 12 months after response.

Adverse events that occurred in at least20% of patients in the trial included laboratory abnormalities such as infection, fatigue, nausea, diarrhea, dyspnea, cough, edema, bleeding, abdominal pain, musculoskeletal pain, headache, decreased phosphate, increased gamma-glutamyl transferase, lymphopenia, and hypertension.

Reference: https://www.targetedonc.com/view/gvhd-treatments-pegtarazimod-and-belumosudil-make-international-inroads