Efficacy and Safety of Cryopreserved Formulation of Autologous CD34+ Hematopoietic Stem Cells Transduced Ex Vivo With Elongation Factor 1 Alpha Shortened (EFS) Lentiviral Vector Encoding for Human ADA Gene in Subjects With Severe Combined Immunodeficiency Due to ADA Deficiency

This is a prospective, non-randomized, single-cohort, longitudinal, single-center, clinical study designed to assess the efficacy and safety of a cryopreserved formulation of OTL-101 (autologous CD34+ hematopoietic stem/progenitor cells transduced ex vivo with EFS (Elongation Factor 1α Short form) Lentiviral Vector (LV) encoding for the human ADA gene) administered to ADA-SCID subjects between the ages of 30 days and 17 years of age, who are not eligible for an Human Leukocyte Antigen (HLA) matched sibling/family donor and meeting the inclusion/exclusion criteria. The OTL-101 product is infused after a minimal interval of at least 24 hours following the completion of reduced intensity conditioning. For subjects who successfully receive the OTL-101 product, pegademase bovine (PEG-ADA) Enzyme Replacement Therapy (ERT) is discontinued at Day+30 (-3/+15) after the transplant. After their discharge from hospital, the subjects will be seen at regular intervals to review their history, perform examinations and draw blood samples to assess immunity and safety.

Start Date16 Dec 2016

Sponsor / Collaborator

University of California, Los Angeles

[+2]

NCT01420627 / CompletedPhase 3

A Study of EZN-2279 (Polyethylene Glycol Recombinant Adenosine Deaminase [PEG-rADA]) Administered as a Weekly Intramuscular Injection in Patients With Adenosine Deaminase (ADA)-Deficient Combined Immunodeficiency

The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of EZN-2279 in patients with ADA-deficient combined immunodeficiency currently being treated with Adagen.

Start Date24 Jan 2014

Sponsor / Collaborator

Leadiant Biosciences, Inc.

NCT01852071 / CompletedPhase 1/2IIT

Autologous Transplantation of Bone Marrow CD34+ Stem/Progenitor Cells After Addition of a Normal Human ADA Complementary DNA (cDNA) by the EFS-ADA Lentiviral Vector for Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID)

The aim of this study is to assess the safety and efficacy of autologous transplantation of hematopoietic stem cells (CD34+ cells) from the bone marrow (BM) of ADA-deficient SCID infants and children following human ADA cDNA transfer by the EFS-ADA lentiviral vector. The level of gene transfer in blood cells and immune function will be measured as endpoints.

Start Date02 Aug 2013

Sponsor / Collaborator

University of California, Los Angeles

[+4]

100 Clinical Results associated with Pegademase

100 Translational Medicine associated with Pegademase

100 Patents (Medical) associated with Pegademase

Literatures (Medical) associated with Pegademase

01 Jul 2024·Journal of Clinical Immunology

Treatment with Elapegademase Restores Immunity in Infants with Adenosine Deaminase Deficient Severe Combined Immunodeficiency

Article

Author: Bali, Pawan ; Mousallem, Talal ; Tarrant, Teresa K ; Hicks, Elizabeth Daly ; Buckley, Rebecca H ; Hall, Geoffrey ; Sleasman, John W ; Hershfield, Michael S

AbstractPurposePatients with adenosine deaminase 1 deficient severe combined immunodeficiency (ADA-SCID) are initially treated with enzyme replacement therapy (ERT) with polyethylene glycol-modified (PEGylated) ADA while awaiting definitive treatment with hematopoietic stem cell transplant (HSCT) or gene therapy. Beginning in 1990, ERT was performed with PEGylated bovine intestinal ADA (ADAGEN®). In 2019, a PEGylated recombinant bovine ADA (Revcovi®) replaced ADAGEN following studies in older patients previously treated with ADAGEN for many years. There are limited longitudinal data on ERT-naïve newborns treated with Revcovi.MethodsWe report our clinical experience with Revcovi as initial bridge therapy in three newly diagnosed infants with ADA-SCID, along with comprehensive biochemical and immunologic data.ResultsRevcovi was initiated at twice weekly dosing (0.2 mg/kg intramuscularly), and monitored by following plasma ADA activity and the concentration of total deoxyadenosine nucleotides (dAXP) in erythrocytes. All patients rapidly achieved a biochemically effective level of plasma ADA activity, and red cell dAXP were eliminated within 2–3 months. Two patients reconstituted B-cells and NK-cells within the first month of ERT, followed by naive T-cells one month later. The third patient reconstituted all lymphocyte subsets within the first month of ERT. One patient experienced declining lymphocyte counts with improvement following Revcovi dose escalation. Two patients developed early, self-resolving thrombocytosis, but no thromboembolic events occurred.ConclusionRevcovi was safe and effective as initial therapy to restore immune function in these newly diagnosed infants with ADA-SCID, however, time course and degree of reconstitution varied. Revcovi dose may need to be optimized based on immune reconstitution, clinical status, and biochemical data.

01 Apr 2024·Annals of Pharmacotherapy

A Real-World Disproportionality Analysis of Drug-Induced Immune Hemolytic Anemia in the FDA Adverse Event Reporting System

Article

Author: Li, Hongying ; Ding, Chuanhua ; Tang, Linlin ; Yin, Guoqiang ; Zhou, Xueheng

Background: Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening pharmacogenic hematological adverse effect. Updating the risk of DIIHA among the currently available drugs based on spontaneously reported adverse event data is of great significance. Objective: This study aimed to identify the top 50 drugs associated with immune hemolytic anemia in adults as well as common drugs that could cause immune hemolytic anemia in children based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: We extracted adverse events (AE) in the FAERS database from Q1 2004 to Q3 2022 using Open vigil2.1. We use the high-level term “anaemias haemolytic immune” according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary (version 24.0). The reported correlation between drugs and DIIHA risk was identified by reported odds ratio (ROR) and proportional reporting ratio (PRR). Results: There were 10500309 AEs in FAERS from 2004Q1 to 2022Q3, of which 2326 (0.02%) were DIIHA cases. The incidence of DIIHA is comparable between males and females. The most common drugs associated with DIIHA in adults and children are summarized according to the number of AE reports. The top 3 categories in terms of quantity of drugs are antineoplastic agents, immunosuppressants, and antibiotics for systemic use. The top 5 drugs in terms of ROR and PRR are alemtuzumab, daclizumab, fludarabine, busulfan, and bendamustine in adults, with entecavir, treosulfan, vinorelbine, pegademase, and alemtuzumab for children. Conclusions: Our study identified the most common drugs that could induce DIIHA in adults and children, as well as the respective ROR and PRR value to discover new drug signals. This study provides references to clinicians for the management of rare DIIHA.

01 Jul 2023·Journal of Clinical Immunology

PEGylated Recombinant Adenosine Deaminase Maintains Detoxification and Lymphocyte Counts in Patients with ADA-SCID

Article

Author: Wiley, Joseph M ; Lehman, Heather ; Haddad, Elie ; Dorsey, Morna J ; Rubinstein, Arye ; Fausnight, Tracy

Abstract PurposeMetabolic detoxification with enzyme replacement therapy (ERT) promotes immune recovery in patients with adenosine deaminase (ADA)–deficient severe combined immunodeficiency (ADA-SCID). Elapegademase is a PEGylated recombinant bovine ADA ERT developed to replace the now-discontinued bovine-derived pegademase. This study was a 1-way crossover from pegademase to elapegademase in 7 patients with ADA-SCID to assess efficacy and safety outcomes for elapegademase.MethodsAfter once-weekly pegademase dosage was adjusted to achieve therapeutic metabolic detoxification and trough ADA activity, patients transitioned to a bioequivalent dose of elapegademase. Maintenance of metabolic detoxification and adequate ADA activity were evaluated periodically.ResultsOne patient withdrew after 2 doses of an early elapegademase formulation due to injection-site pain caused by EDTA. The 6 remaining patients completed 71−216 weeks of elapegademase therapy with a formulation that did not contain EDTA. In these patients, elapegademase improved ADA activity compared with pegademase and maintained metabolic detoxification. Total lymphocyte counts increased for all completer patients from between 1.2- and 2.1-fold at the end of study compared with baseline. Elapegademase had a comparable safety profile to pegademase; no patient developed a severe infectious complication. Three patients had transient, non-neutralizing antibodies to pegademase, elapegademase, and/or polyethylene glycol ≤ 47 weeks of treatment without effect on trough plasma ADA activity or trough erythrocyte deoxyadenosine nucleotide levels.ConclusionElapegademase was safe, well tolerated, achieved stable trough plasma ADA activity with weekly dosing, was effective in maintaining metabolic detoxification, and was associated with maintenance or improvements in lymphocyte counts compared with pegademase therapy in patients with ADA-SCID.

100 Deals associated with Pegademase

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Indication	Country/Location	Organization	Date
Adenosine deaminase deficiency	JP	Teijin Pharma Ltd.	01 May 2019

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02999984 (CTgov)	Phase 1/2	Adenosine deaminase deficiency	10	Busulfan+Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101)+PEG-ADA ERT	xexmzrxmau(fzptfahktk) = brcdiwljzr ypqopufrhe (pphhtqthwe, ddeysmchjx - cwrxmxkddb) View more	-	22 Jul 2022

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