Delving into the Latest Updates on Elapegademase-LVLR with Synapse

Overview

Basic Info

Drug Type

Enzyme

Synonyms

Elapegademase, Elapegademase (Genetical Recombination), PEG-rADA

+ [8]

Target

Adenosine

Mechanism

Adenosine deaminase replacements

Therapeutic Areas

Immune System DiseasesCongenital DisordersEndocrinology and Metabolic Disease+ [2]

Active Indication

Adenosine deaminase deficiency

Inactive Indication-

Originator Organization

Leadiant Biosciences, Inc.

Active Organization

Chiesi USA, IncTeijin Pharma Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (05 Oct 2018),

Adenosine deaminase deficiency

RegulationOrphan Drug (JP), Fast Track (US), Priority Review (US)

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Gene Sequence

Sequence Code 84574

Source: *****

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 Oct 2023·Journal of clinical immunology

Correction to: PEGylated Recombinant Adenosine Deaminase Maintains Detoxification and Lymphocyte Counts in Patients with ADA-SCID.

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

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 Elapegademase-LVLR

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