Long-term Follow-up of Patients Participating in RACE: the Prospective Randomized Multicenter Study Comparing Horse Antithymocyte Globuline (hATG) + Cyclosporine A (CsA) With or Without Eltrombopag as Front-line Therapy for Severe Aplastic Anemia Patients

After exiting the RACE trial (NCT02099747) patients will be invited to participate in this long term follow-up study

开始日期2021-10-01

申办/合作机构-

NCT03025698

/ Completed临床2期

A Phase II, Open-label, Non-controlled, Intra-patient Dose-escalation Study to Characterize the Pharmacokinetics After Oral Administration of Eltrombopag in Pediatric Patients With Refractory, Relapsed or Treatment Naive Severe Aplastic Anemia or Recurrent Aplastic Anemia

This is a phase II, open label, multi-center, intra-patient dose escalation study to characterize the pharmacokinetics (PK) after oral administration of eltrombopag in combination with immunosuppressive therapy in pediatric patients with previously untreated or relapsed/refractory severe aplastic anemia or recurrent aplastic anemia.

开始日期2017-09-30

申办/合作机构

Novartis Pharmaceuticals Corp.

NCT00944749

/ Completed临床2期IIT

Horse ATG/CsA in Aplastic Anemia Patients Unresponsive to or With a Suboptimal Response to Rabbit ATG/CsA Treatment

Background:
* Severe plastic anemia can lead to problems with bone marrow platelet production and result in low blood platelet counts, which require frequent platelet transfusions to improve blood clotting.
* A standard treatment for SAA involves injections of rabbit-antithymocyte globulin (r-ATG). r-ATG is developed by injecting horses with a type of human white blood cells called thymocytes. The horse's immune system reacts against these cells and makes antibodies that can destroy them. These antibodies are collected and purified to make r-ATG. Horses can also be used for this procedure to make horse-antithymocyte globulin (h-ATG).
* h-ATG is approved by the Food and Drug Administration for the treatment of aplastic anemia. h-ATG is a standard first-line method to treat aplastic anemia, but researchers do not know how effective it is in patients who were first treated unsuccessfully with r-ATG.
Objectives:
- To evaluate the effectiveness and safety of horse-ATG (with cyclosporine) in increasing blood counts and reducing the need for transfusions in aplastic anemia patients who have failed to respond to prior immunosuppressive treatment with rabbit-ATG and cyclosporine.
Eligibility:
- Patients 2 years of age and older who have consistently low blood platelet counts related to aplastic anemia that has not responded to conventional treatment with rabbit-ATG.
Design:
* After initial screening, medical history, and blood tests, patients will be admitted to the inpatient unit at the National Institutes of Health Clinical Center. Researchers will perform a skin test with h-ATG to check for allergic or other adverse reaction.
* After the skin test, h-ATG will be given into a vein continuously over 4 days.
* Cyclosporine will also be given to improve the response rate of ATG treatment. Treatment with cyclosporine will start the same day as the h-ATG, either in liquid or capsule form, and continued for 6 months. The dose of cyclosporine will be monitored and adjusted based on blood levels and signs of side effects in the kidney and liver.
* To prevent or treat infections that may result from cyclosporine s effect on the immune system, patients will also take inhaled or capsule doses of pentamidine.
* After the study is completed, patients will have followup evaluations every 3 months, 6 months, and annually for 5 years. Evaluations will include blood samples and periodic bone marrow biopsies.

开始日期2009-08-31

申办/合作机构

National Heart, Lung & Blood Institute

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100 项与 Lymphocyte Immune Globulin, Anti-thymocyte Globulin (Equine) 相关的专利（医药）

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项与 Lymphocyte Immune Globulin, Anti-thymocyte Globulin (Equine) 相关的文献（医药）

2025-08-21·BLOOD

Imaging mass cytometry reveals the order of events in the pathogenesis of immune-mediated aplastic anemia

Article

作者: Heemskerk, Mirjam H. M. ; Luk, Sietse J. ; de Miranda, Noel F. C. C. ; Ijsselsteijn, Marieke E. ; Falkenburg, J. H. Frederik ; Tjon, Jennifer M.-L. ; van Unen, Vincent ; Koning, Frits ; Pool, Emma S.

Abstract:

The autoimmune response driving hematopoietic stem and progenitor cell (HSPC) destruction in immune-mediated aplastic anemia (AA) remains incompletely understood. We previously identified a disease-specific immune cell network involving T, B, and myeloid cells. However, the interactions within this network, the interaction with the microenvironment, and the chronological events in AA development, remain unclear. In this study, we aimed to characterize the changes occurring during disease development and to define the interactions between potential autoreactive cells and their target. Using imaging mass cytometry, we analyzed bone marrow (BM) biopsies from patients with AA at diagnosis and after treatment with horse-derived anti–thymocyte globulin (hATG), and 6 controls. Within the hypocellular BM architecture, we identified lymphoid-dominant “immune hot spots” with high densities of proinflammatory lymphocytes, and macrophage-enriched hot spots that additionally contained activated macrophages in proximity to progenitors. These immune hot spots potentially represent sites in which the active immune response resulting in HSPC destruction takes place. In BM regions depleted of progenitors, effector cells with a differentiated phenotype remain. Our data indicate that HSPC destruction in AA is mediated by coordinated interactions among specific immune cell subpopulations. As the immune response progresses and HSPCs are depleted, the immune composition shifts, with activated T and B cells differentiating into terminally differentiated T cells and plasma cells. In patients with normalizing BM after hATG treatment, most immune hot spots were depleted, underscoring their potential pathogenic role. Collectively, our study visualizes the complex interactions among immune cell subpopulations and reveals, to our knowledge, for the first time, the order of events in the immune-mediated pathogenesis of AA.

2025-08-01·CYTOTHERAPY

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

Article

作者: Muzalevsky, Yakov ; Maschan, Michael ; Shasheleva, Darya ; Kozlovskaya, Svetlana ; Dunaykina, Maria ; Kurnikova, Elena ; Zavidnyi, Timofei ; Brilliantova, Varvara ; Ilyushina, Maria ; Goronkova, Olga ; Shelikhova, Larisa ; Klimentova, Maria ; Baydildina, Dina ; Pershin, Dmitry ; Balashov, Dmitry ; Perminova, Margarita ; Novichkova, Galina ; Maschan, Alexey ; Kazachenok, Alexey

BACKGROUND AIMS:

Hematopoietic stem cell transplantation (HSCT) from matched unrelated donor (MUD) is a curative option for severe aplastic anemia (SAA) patients, refractory to horse anti-thymocyte globulin (ATG) and cyclosporin A (CsA) mmunosuppression. Although the results of MUD HSCT in SAA have improved significantly, graft-versus host disease (GVHD) remains a serious problem, associated with significant morbidity and mortality. We investigated the role of alpha/beta T cell depletion of the graft as a way to improve the results of MUD HSCT in SAA.

METHODS:

Forty-seven patients with SAA were treated since September 2012 till February 2022. Median age at HSCT was 12.4 (3-22.7) years, 26 males/21 females. All patients were either refractory or relapsed (35:12) after combined immune suppression therapy, 5 pts had concurrent severe hemolytic paroxysmal nocturnal hemoglobinuria (PNH). The median time from diagnosis to transplant was 1.2 years (0.5-11.8 years). Preparative regimen included cyclophosphamide 100 mg/kg, fludarabine 150 mg/kg, ATGAM at 100 mg/kg (27pts) or thymoglobulin 5 mg/kg (15 pts) and 6 Gy thoraco-abdominal irradiation. Thiotepa at 10 mg/kg and rituximab at 200 mg/m² were used in a proportion of cases. Patients with PNH (n = 5) received eculizumab 600 mg once every 7 days from -7 to +14 days. Post-transplant GVHD prophylaxis included tacrolimus till day 180. Peripheral blood stem cell (PBSC) grafts were depleted of T cell receptor (TCR) alpha/beta cells and CD19 cells with CliniMACS device, as recommended by the manufacturer. Patients received a median of 9.2 (2.7-18.30) х10⁶ CD34 per kg, 21.8 (0.85-316)x10³ αβ T cells per kg.

RESULTS:

Forty-six patients (cumulative incidence (CI) 0.96 (95% 0.9-1)) engrafted with a median of 14 (7-24) days for white blood cells (WBC) and 12 (9-18) days for platelets. In 8 patients after MUD transplantation secondary graft failure (rejection) developed, cumulative incidence was 0.15 (95% 0.08-0.3), three of them was successfully retransplanted. CI of acute graft-versus host disease (aGVHD) grade II-IV was 0.15 (95% 0.08-0.29). No cases of grade III-IV aGVHD were registered. CI of chronic graft versus host disease (cGVHD) was 0.11 (95% 0.05-0.25). All were mild and off-IST at last follow-up. A median follow-up is 9 years. Ten patients died. At a median follow-up of 9 years, the overall survival was 79% (67-90). Failure-free survival was 72% (60-85) and the GRFS was 72% (60-85).

CONCLUSIONS:

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.

2025-01-01·[Rinsho ketsueki] The Japanese journal of clinical hematology

[A new era in the treatment of aplastic anemia].

Review

作者: Hosokawa, Kohei

Aplastic anemia (AA) is a rare hematologic disorder characterized by bone marrow hypoplasia and pancytopenia, and is classified into idiopathic and secondary forms. Idiopathic AA is primarily treated with immunosuppressive therapy (IST), thrombopoietin receptor agonists (TPO-RAs), and hematopoietic stem cell transplantation (HSCT). 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.

项与 Lymphocyte Immune Globulin, Anti-thymocyte Globulin (Equine) 相关的新闻（医药）

2023-04-03

·Firstwordpharma

CMS trims first list of drugs tapped for inflation fines

The US Centers for Medicare and Medicaid Services (CMS) has quietly updated the list of Part B prescription medicines subject to penalties because their prices rose faster than the rate of inflation. In an update late last week, the agency cut seven medicines from its original list of 27 that was unveiled on March 15.A provision in the Inflation Reduction Act (IRA), which came into force last year, penalises pharmaceutical companies for charging prices that go up faster than inflation for people with disabilities or those 65 and older who are on the government's Medicare health programme (for more, see ViewPoints: Inflation Reduction Act's myriad impacts to reverberate across pharma). The move is expected to lower out-of-pocket costs for some Medicare recipients by between $1 and $372 per average dose, as of April 1, depending on their individual coverage, according to an agency press release updated on March 30.Gilead cell therapies knocked off The seven drugs that have been cut from the original list include Gilead Sciences' CAR-T therapies Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel); Stemline Therapeutics' Elzonris (tagraxofusp-erzs) used for blastic plasmacytoid dendritic cell neoplasm; Shionogi's Fetroja (cefiderocol), an antibiotic to treat complicated urinary tract infections; Arcotech Biopharma's Folotyn (pralatrexate) for relapsed or refractory peripheral T-cell lymphoma; Kamada's WinRho SDF (Rhₒ(D) immune globulin) to boost platelet counts in order to prevent excessive haemorrhage; and Bausch + Lomb's Xipere (triamcinolone acetonide), which is prescribed for macular oedema associated with uveitis.CMS did not give a reason for why the original list was scaled back. Other products that remain include all five Pfizer drugs that were on the original list, namely Atgam (antithymocyte globulin equine), Bicillin L-A (penicillin G benzathine), Bicillin C-R (penicillin G benzathine and penicillin G procaine), Fragmin (dalteparin) and Nipent (pentostatin), as well as Johnson & Johnson's Rybrevant (amivantamab). Companies whose products have been flagged will be required to pay Medicare the difference in the form of a rebate ranging from roughly 14% to 20%. Meanwhile, CMS has said that by September 1, it plans to publish the first 10 Medicare Part D drugs that will be subject to government price negotiations starting in 2026.

生物类似药上市批准加速审批申请上市专利到期

2023-03-16

·PMLiVE

US government announces first set of drugs subject to Medicare inflation rebates

The US government has announced the first set of drugs that will be subject to penalties because their prices rose faster than the rate of inflation, a move set to reduce out-of-pocket costs for certain Medicare beneficiaries by up to $390 per dose. The 27 products, which all fall under Medicare Part B, include Gilead Sciences’ blood cancer therapies Yescarta and Tecartus, AbbVie’s immunology drug Humira, Seagen’s Padcev for bladder cancer and Roche’s lung cancer therapy Rybrevant. Five of Pfizer’s drugs are also listed, including the blood thinner Fragmin, Atgam for allograft rejection in renal transplant patients, chemotherapy Nipent, and antibacterial drugs Bicillin L-A and Bicillin C-R. A penalty equivalent to 125% of the rebate amount will be given to those that fail to pay, with the first demands for payment due to go out in 2025. Eligible Medicare recipients will be able to start paying the lower coinsurance amount next month. The announcement comes as a result of President Biden’s Inflation Reduction Act, which requires drug companies to pay rebates to Medicare when their prices increase faster than the rate of inflation. US Department of Health and Human Services secretary, Xavier Becerra, said: “The Biden-Harris administration believes people with Medicare shouldn’t be on the hook when drug companies inexplicably jack up the prices of their drugs. “President Biden made lowering prescription drug costs for Americans a top priority and we’re using every lever we have to deliver results. With the inflation rebate programme, we are fighting to ensure seniors can afford the treatments they need, taxpayers aren’t subsidising drug company excess prices, and the Medicare programme is strong for millions of beneficiaries now and in the future.” Tackling the high costs of prescription drugs and increasing access to novel therapies has been a key focus of the current US government. Last month, the US health department proposed three new models to help promote accessibility and improve quality of care for those enrolled in voluntary government health insurance plans. Included in the proposals is a model encouraging the Medicare Part D plans, which cover the cost of most prescriptions, to offer a monthly $2 fixed co-payment for commonly used generic drugs for chronic conditions, such as high blood pressure.

加速审批

2023-03-15

·Endpoints

Five Pfizer drugs among first 27 now subject to Medicare inflation rebates, HHS says

The Department of Health and Human Services (HHS) on Wednesday unveiled the first set of 27 Part B prescription drugs, including five from Pfizer, that will be subject to Medicare inflation rebates because their prices rose faster than the rate of inflation. Seniors receiving the physician-administered drugs beginning in April will have lower coinsurance for these drugs (listed below) and HHS said they may see their out-of-pocket costs for these drugs decrease by as much as $390 per average dose. “In addition to making drug companies pay Medicare back for increasing their prices faster than inflation, this provision of the Inflation Reduction Act discourages other companies from doing the same, with the goal of reining in excessive drug price hikes year-over-year,” the White House said in a fact sheet released this morning. zMoving forward, CMS said, beneficiary coinsurance will be 20% of the inflation-adjusted payment amount for the following drugs: Usual suspects like AbbVie’s Humira will be subject to biosimilar competition beginning this year so the price will likely come down. But for other drugs without competitors, the price increases continue apace, such as with Gilead subsidiary Kite Pharma’s CAR-T cancer therapy Yescarta, which saw its list price rise by more than $70,000 per dose with that nearly 20% price increase. The five Pfizer drugs include older drugs like the blood thinner Fragmin (dalteparin), which first won FDA approval in 1994; Atgam, which is for allograft rejection in renal transplant patients; and the chemo Nipent (pentostatin), as well as antibacterial drugs, Bicillin L-A and Bicillin C-R. In addition to this list, the White House also put out a report Wednesday explaining how seniors will see more than $230 million in savings this year when the more than 3.4 million people with Medicare begin to pay no out-of-pocket costs for recommended vaccines. Medicare beneficiaries in the Dakotas, Montana and Wyoming will see the biggest savings from the IRA-related change related to no OOP costs for recommended vaccines.

上市批准疫苗加速审批

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适应症	国家/地区	公司	日期
再生障碍性贫血	美国	Pharmacia & Upjohn LLC	1996-12-04
肾移植排斥反应	美国	Pharmacia & Upjohn LLC	1996-12-04

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ATGAM Temporary Use Authorization program (ASH2023)	N/A	再生障碍性贫血一线	634	ATGAM 40 mg/kg	築鑰顧願艱淵鬱願遞構(壓積壓壓醖蓋艱衊廠構) = 鹽淵醖壓選鹽廠齋製壓鹽鏇選淵網鹽鏇鑰餘膚 (壓餘鑰蓋艱顧觸築獵糧 ) 更多	积极	2023-12-09
NCT00176930 (CTgov)	N/A	急性髓性白血病 \| 霍奇金淋巴瘤 \| 慢性淋巴细胞白血病 ... 更多	330	Stem Cell Transplant+Busulfan+Cyclophosphamide (PBSC: No TBI)	製鑰鹽簾醖餘積餘壓蓋 = 觸膚繭襯範窪選壓獵鬱範壓製鹽衊夢齋鬱憲襯 (鹽餘顧淵鑰繭蓋顧簾鹹, 窪鹹艱積顧顧壓製製壓 ~ 鬱簾膚遞簾鏇積膚衊獵) 更多	-	2021-01-22
NCT00176930 (CTgov)	N/A	急性髓性白血病 \| 霍奇金淋巴瘤 \| 慢性淋巴细胞白血病 ... 更多	330	Stem Cell Transplant+Busulfan+Cyclophosphamide (Marrow : No TBI)	製鑰鹽簾醖餘積餘壓蓋 = 製鑰糧鑰選壓築膚醖憲範壓製鹽衊夢齋鬱憲襯 (鹽餘顧淵鑰繭蓋顧簾鹹, 蓋積衊選夢鬱願願繭選 ~ 遞餘選壓範鏇壓憲夢簾) 更多	-	2021-01-22