Atgam (equine anti-thymocyte globulin) / Pfizer - LARVOL DELTA

Atgam Efficacy and Safety in Moderate-to-Very Severe Acquired Aplastic Anemia: Outcome of a Large Multicenter Cohort of 634 Children and Adults from the French Authorization for Temporary Use Surveillance Program (ASH 2023) - "Results In total, 634 patients with moderate-to-very severe AA were treated with ATGAM (n=537 first-line; n=68 refractory/relapse; n=29 not classified) in addition to cyclosporine (40 first-line patients also received eltrombopag) from January 2012 to August 2022. No new safety risks were identified in this large cohort of patients. Treatment with ATGAM remains of benefit in patients with moderate-to-very severe AA."

Clinical • Anemia • Aplastic Anemia • Hematological Disorders • Immunology

Long-term outcomes of αβ T-cell/CD19 B-cell-depleted peripheral blood stem cell transplantation from unrelated donors in pediatric and adolescent patients with severe aplastic anemia: a single-center study. (PubMed, Cytotherapy) - "TCR alpha/beta depletion is a robust platform for allogeneic HSCT from MUD in severe aplastic anemia. Results should be further improved by additional measures to control viral infections and prevent rejection."

Journal • Acute Graft versus Host Disease • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Complement-mediated Rare Disorders • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Pediatrics • Rare Diseases • Transplantation • CD34

A Trial Comparing Unrelated Donor BMT With IST for Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202) (clinicaltrials.gov) - P3 | N=53 | Active, not recruiting | Sponsor: Boston Children's Hospital | Recruiting ➔ Active, not recruiting | N=234 ➔ 53

Enrollment change • Enrollment closed • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Hematological Disorders • Pediatrics • Transplantation • HLA-B • HLA-C • HLA-DQB1 • HLA-DRB1

Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases (clinicaltrials.gov) - P2 | N=53 | Active, not recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial primary completion date: Jun 2025 ➔ Dec 2025

Trial primary completion date • CNS Disorders • Immunology • Movement Disorders • Multiple Sclerosis • Myasthenia Gravis • Neuromyelitis Optica Spectrum Disorder • Pain • Rare Diseases • Transplantation • Vasculitis

A new era in the treatment of aplastic anemia (PubMed, Rinsho Ketsueki) - "Cyclosporine (CsA) monotherapy is recommended for patients who have mild disease or are moderately transfusion-independent, whereas the combination of anti-thymocyte globulin (ATG) and CsA is the standard treatment for severe disease. In 2023, equine ATG (ATGAM®) was approved in Japan, expanding the options for IST. TPO-RA options for combination therapy with IST now include romiplostim in addition to eltrombopag, and studies have demonstrated the efficacy of triple combination therapy with ATG, CsA, and a TPO-RA has been demonstrated. In the context of HSCT, HLA-haploidentical transplantation using post-transplant cyclophosphamide is increasingly being considered as an option for patients without an HLA-matched donor due to its improved safety and efficacy. This review provides a comprehensive overview of the latest advances in AA treatment, including novel therapeutic strategies, and discusses future therapeutic directions to further improve patient outcomes."

Journal • Review • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Hematological Disorders • Transplantation

ATGAM versus Thymoglobulin in Kidney Transplant Tolerance Induction in Non-Human Primates (WTC 2025) - "Therefore, we aim to evaluate rabbit anti-thymocyte globulin (Thymoglobulin) as an alternative T-cell depleting agent for tolerance induction through the mixed chimerism approach.* MHC mismatched cynomolgus monkeys underwent a preconditioning regimen consisting of 1.5 Gy total body irradiation, a peri-transplant course of a Bcl-2 inhibitor (Venetoclax 10mg/kg from day -4 to day +6), 7 Gy local thymic irradiation and either ATGAM (50mg/kg on days -2, -1 and 0; n=8) or Thymoglobulin (5mg/kg on days -1 and 0; n=6)...All recipients then underwent combined kidney and bone marrow transplantation (CKBMT) and received anti-CD154 mAb (20mg/kg on days 0, 2, 5 and 12) along with a 28-day course of cyclosporine, after which no immunosuppression was administered... Compared to Thymoglobulin, using ATGAM as part of a chimerism based tolerance induction strategy promoted longer-lasting myeloid and lymphoid chimerism with a lower rate of rejection but similar overall graft survival...."

Bone Marrow Transplantation • Infectious Disease • Transplant Rejection • Transplantation • CD40LG

Emerging Trends in List Price Adjustment Strategies Following Implementation of the Inflation Reduction Act (ISPOR 2025) - "Among products analyzed, Pfizer’s Atgam experienced the largest price increase at +15%. In contrast, significant price decreases were observed for Boehringer Ingelheim’s Atrovent (-35%) and Merck’s Januvia and Janumet/Janumet XR (-42.4%)...Excluding Januvia, the year-over-year (YoY) percent change in price for the six other IRA negotiation products with 2025 data declined from +4.0% in 2024 to +2.4% in 2025; Eliquis had the largest shift YoY from +6% in 2024 to +2% in 2025... List price adjustments reflect both product-specific and broader industry dynamics. In anticipation of IRA negotiations, IRA products are experiencing lower than average price increases. As government regulations evolve and pricing pressure on pharmaceuticals increase, assessing price adjustments in the context of anticipated payer management and government penalties will be a key consideration for manufacturers."

Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia (clinicaltrials.gov) - P=N/A | N=40 | Completed | Sponsor: Michael Pulsipher | Active, not recruiting ➔ Completed

Trial completion • Anemia • Aplastic Anemia • Hematological Disorders • Pediatrics • Transplantation • HLA-B • HLA-C • HLA-DQB1 • HLA-DRB1

TRIUMPH: TReatment for ImmUne Mediated PathopHysiology (clinicaltrials.gov) - P2 | N=163 | Recruiting | Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | Trial completion date: Jan 2027 ➔ May 2027 | Trial primary completion date: Jan 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • CNS Disorders • Hepatic Encephalopathy • Hepatology • Liver Failure • Pediatrics

COMPARISON OF OUTCOMES OF IMMUNOSUPPRESSIVE THERAPY WITH RABBIT VS. HORSE ANTI-THYMOCYTE GLOBULIN AND CYCLOSPORINE A IN PATIENTS WITH REFRACTORY CYTOPENIA OF CHILDHOOD ​ (EBMT 2025) - " We report the outcomes of IST in 133 children (80 males/53 females) with RCC and treated with either h-ATG (Atgam®, n=64) or r-ATG (Thymoglobulin®, n=69) and cyclosporine A. The median age at diagnosis was 9.0 (1.7-18.1) years...Eltrombopag was added on day 344 in one patient... The results suggest that IST with both h-ATG and r-ATG is an effective therapy, achieving a response rate of approximately 50% in RCC patients. Although no significant differences were observed in response rate or FFS between the two ATG groups, OS was higher in patients receiving h-ATG, indicating a potential advantage of h-ATG. Patients with persistent severe neutropenia face a high risk of mortality and should be considered for early second-line HSCT."

Clinical • Preclinical • Acute Myelogenous Leukemia • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Renal Cell Carcinoma • Septic Shock

COMPARISON OF OUTCOMES OF IMMUNOSUPPRESSIVE THERAPY WITH RABBIT VS. HORSE ANTI-THYMOCYTE GLOBULIN AND CYCLOSPORINE A IN PATIENTS WITH REFRACTORY CYTOPENIA OF CHILDHOOD ​ (EBMT 2025) - " We report the outcomes of IST in 133 children (80 males/53 females) with RCC and treated with either h-ATG (Atgam®, n=64) or r-ATG (Thymoglobulin®, n=69) and cyclosporine A. The median age at diagnosis was 9.0 (1.7-18.1) years...Eltrombopag was added on day 344 in one patient... The results suggest that IST with both h-ATG and r-ATG is an effective therapy, achieving a response rate of approximately 50% in RCC patients. Although no significant differences were observed in response rate or FFS between the two ATG groups, OS was higher in patients receiving h-ATG, indicating a potential advantage of h-ATG. Patients with persistent severe neutropenia face a high risk of mortality and should be considered for early second-line HSCT."

Clinical • Preclinical • Acute Myelogenous Leukemia • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Renal Cell Carcinoma • Septic Shock

IN VIVO EFFECTS AND PHARMACODYNAMICS OF ATGAM IN ACQUIRED APLASTIC ANEMIA PATIENTS (EBMT 2025) - "The first-line treatment for most AA patients is immunosuppressive therapy (IST), consisting of 4 consecutive days 40 mg/kg/day horse-derived anti-thymocyte globulin (ATGAM®) and long-term ciclosporin. This study provides unique insight into the pharmacokinetics and pharmacodynamics of ATGAM in AA patients. We found that patients with a higher body weight have higher ATGAM exposures, which tend to correlate with improved hematologic recovery. Additionally, our analyses demonstrate that the therapeutic effect of ATGAM may be linked to the targeted depletion of specific lymphoid populations."

PK/PD data • Preclinical • Anemia • Aplastic Anemia • Hematological Disorders • Immunology

IN VIVO EFFECTS AND PHARMACODYNAMICS OF ATGAM IN ACQUIRED APLASTIC ANEMIA PATIENTS (EBMT 2025) - "The first-line treatment for most AA patients is immunosuppressive therapy (IST), consisting of 4 consecutive days 40 mg/kg/day horse-derived anti-thymocyte globulin (ATGAM®) and long-term ciclosporin. This study provides unique insight into the pharmacokinetics and pharmacodynamics of ATGAM in AA patients. We found that patients with a higher body weight have higher ATGAM exposures, which tend to correlate with improved hematologic recovery. Additionally, our analyses demonstrate that the therapeutic effect of ATGAM may be linked to the targeted depletion of specific lymphoid populations."

PK/PD data • Preclinical • Anemia • Aplastic Anemia • Hematological Disorders • Immunology

Stem Cell Transplantation in Crohn's Disease (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: Cedars-Sinai Medical Center | Trial completion date: Jan 2025 ➔ Sep 2026 | Trial primary completion date: Jan 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease • Transplantation

Response to Immunosuppressive Therapy in Aplastic Anemia-A Single Centre, Prospective Study of 158 Patients from a Tertiary Care Centre in India. (PubMed, Indian J Hematol Blood Transfus) - "Immunosuppressive therapy (IST) with Antithymocyte globulin (ATG) and cyclosporine is the therapy of choice in aplastic anemia (AA) patients who are more than 40 years of age and younger patients who do not have matched sibling donor for stem cell transplant (SCT)...The two preparations of ATG that are available in India are Atgam (Pfizer) and Thymogam (Bharat serum, India)...Age, Gender and severity at presentation did not influence response rates. The online version contains supplementary material available at 10.1007/s12288-024-01794-y."

Journal • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Hematological Disorders • Transplantation

Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases (clinicaltrials.gov) - P2 | N=53 | Active, not recruiting | Sponsor: Fred Hutchinson Cancer Center | Trial primary completion date: Jan 2025 ➔ Jun 2025

Trial primary completion date • Bone Marrow Transplantation • CNS Disorders • Immunology • Movement Disorders • Multiple Sclerosis • Myasthenia Gravis • Neuromyelitis Optica Spectrum Disorder • Pain • Rare Diseases • Transplantation • Vasculitis

Scleroderma Treatment With Autologous Transplant (STAT) Study (clinicaltrials.gov) - P2 | N=21 | Completed | Sponsor: Fred Hutchinson Cancer Center | Active, not recruiting ➔ Completed

Trial completion • Immunology • Scleroderma • Systemic Sclerosis • Transplantation

ATGAM General Investigation (clinicaltrials.gov) - P=N/A | N=5 | Active, not recruiting | Sponsor: Pfizer | N=100 ➔ 5 | Trial completion date: Feb 2026 ➔ Jan 2027 | Trial primary completion date: Feb 2026 ➔ Jan 2027

Enrollment change • Trial completion date • Trial primary completion date • Anemia • Aplastic Anemia • Hematological Disorders

Gemcitabine Hydrochloride, Clofarabine, and Busulfan Before Donor Stem Cell Transplant in Treating Patients With Refractory B-Cell or T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=64 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Jun 2024 | Trial primary completion date: May 2025 ➔ Jun 2024

Trial completion • Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Transplantation • HLA-DRB1

Methylprednisolone, Horse Anti-Thymocyte Globulin, Cyclosporine, Filgrastim, and/or Pegfilgrastim or Pegfilgrastim Biosimilar in Treating Patients With Aplastic Anemia or Low or Intermediate-Risk Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=140 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Anemia • Aplastic Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology

Gemcitabine Hydrochloride, Clofarabine, and Busulfan Before Donor Stem Cell Transplant in Treating Patients With Refractory B-Cell or T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=64 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: May 2024 ➔ May 2025 | Trial primary completion date: May 2024 ➔ May 2025

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Transplantation • HLA-DRB1

Comparing Delayed versus Simultaneous Bone Marrow Transplantation to Achieve Lung Allograft Tolerance in Nonhuman Primates (ATC 2024) - "Group A (n=4) received ATGAM +/- aIL-6R mAb at the time of lung transplant...aIL-6R mAb was given until day 21 and cyclosporine until day 28 post-BMT... Simultaneous lung and BMT did not result in successful induction of lung allograft tolerance. This data suggests that inflammation associated with the lung transplant may create a milieu that prevents successful induction of tolerance and delaying BMT is critical."

Bone Marrow Transplantation • Inflammation • Transplantation

Il-6 Blockade Promotes Tolerance of Heart But Not Lung Allografts in Nonhuman Primate Simultaneous Organ and Bone Marrow Transplantation Protocols (ATC 2024) - "Here, we report the differential effect of adding aIL-6R mAb therapy to a simultaneous mixed-chimerism protocol for heart and lung transplantation.* Fourteen cynomolgus NHPs underwent simultaneous BMT and either heart or lung transplant with non-myeloablative conditioning including total body and thymic irradiation, ATGAM, aCD154 mAb, and cyclosporine until day 28 post-BMT. IL-6 signaling blockade in a simultaneous mixed-chimerism NHP model facilitates long-term immunosuppression-free survival of cardiac but not lung allografts. Lung allografts appear to be particularly prone to rejection and donor chimerism plus IL-6R blockade is not sufficient to induce lung allograft tolerance in this model. Future work will investigate these organ-specific differences to optimize lung tolerance induction."

Clinical • Bone Marrow Transplantation • Solid Organ Transplantation • Transplantation • IL6R

Anti-IL-6 Therapy Prolongs Nonhuman Primate Cardiac Allograft Survival in a Mixed Chimerism Protocol (ATC 2024) - "*Purpose: We previously achieved tolerance of heart allografts in nonhuman primates (NHPs) by blocking the IL-6 receptor with tocilizumab in a mixed-chimerism protocol where donor bone marrow transplantation (BMT) occurred simultaneously with solid organ transplantation. Here, we investigated the effect of blocking the IL-6 cytokine itself with clazakizumab, to prevent the risk of IL-6 cytokine rebound after the cessation of anti-IL-6 receptor treatment.* Nine cynomolgus NHPs underwent simultaneous BMT and heart transplant with non-myeloablative conditioning including total body and thymic irradiation, ATGAM, anti-CD154 mAb, and cyclosporine until day 28 post-BMT... Adding anti-IL-6 mAb treatment to a simultaneous mixed-chimerism conditioning protocol induced prolonged immunosuppression-free cardiac allograft survival without the rise in CRP observed following anti-IL6R mAb therapy. Future in vitro work will investigate the differences between NHPs with prolonged graft..."

Clinical • Late-breaking abstract • Bone Marrow Transplantation • Cardiovascular • Solid Organ Transplantation • Transplantation • CD40LG • CRP

Promotion of Mixed Chimerism by a Synergy between Low Dose Cyclophosphamide Combined with Bcl-2 Inhibitor to Induce Kidney Allograft Tolerance (ATC 2024) - "To extend the application of this strategy to a clinical tolerance protocol based on cyclophosphamide (CP), we investigated the synergistic effects of Bcl-2i and CP in combined kidney and bone marrow transplantation (CKBMT).* Sixteen cynomolgus monkeys underwent CKBMT with a non-myeloablative conditioning regimen, which included CP, local thymic irradiation (7Gy), equine anti-thymocyte globulin (ATGAM), anti-CD154 mAb, and a 28-day course of cyclosporine...In Groups D and E, peri-transplant Bcl-2i (daily Venetoclax 10mg/kg day -4 to +Day 6) was added... As observed with TBI, Bcl-2i promoted hematopoietic chimerism in a CP-based conditioning regimen without severe myelosuppression. The optimal dose of CP to induce sufficient levels of chimerism to achieve allograft tolerance remains to be determined."

Bone Marrow Transplantation • Hematological Disorders • Leukopenia • Transplantation • CD40LG