Revcovi (elapegademase-lvlr) / Teijin, Chiesi - LARVOL DELTA

Elapegademase in Patients with ADA-SCID Previously Treated with Pegademase: A Case Series (CIS 2025) - P, P3 | "Introduction: Elapegademase (Revcovi®), a PEGylated recombinant bovine adenosine deaminase (ADA), is the only FDA-approved enzyme replacement therapy (ERT) for ADA-severe combined immunodeficiency (SCID), replacing pegademase (Adagen® ) since 2018. Four patients with ADA-SCID, diagnosed in infancy (2 males) or early childhood (2 females), began ERT (pegademase) within a year of diagnosis (Table 1). Patient 1 with unsuccessful GT continued ERT. For the other 3, HSCT was not an option."

Clinical • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Immunology • Infectious Disease • Primary Immunodeficiency

Drug-induced herpes zoster: a pharmacovigilance analysis of FDA adverse event reports from 2004 to 2024. (PubMed, Front Pharmacol) - "Anifrolumab exhibited the greatest ROR and PRR ratings among the drugs evaluated. Furthermore, rozanolixizumab, tozinameran, elapegademase, and other medications not indicated for inducing herpes zoster were recognized, underscoring the necessity for increased clinical vigilance and awareness...This study underscores the need of pharmacovigilance in recognizing and comprehending drug-induced herpes zoster. Additional research is required to validate these findings and to design strategies for risk management and reduction to enhance treatment outcomes in patients."

Adverse events • Journal • Herpes Zoster • Varicella Zoster

Multi-Year Registry Study of Elapegademase Treatment in Patients With Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) Requiring Enzyme Replacement Therapy. (PubMed, J Clin Immunol) - P | "Effectiveness of elapegademase was maintained up to 4 years of use and with no new safety concerns."

Journal • Genetic Disorders • Immunology • Infectious Disease • Primary Immunodeficiency

Increased dosage of elapegademase-lvlr improved metabolic andimmunologic function in a patient with late-onset adenosine deaminase deficiency and neutralizing anti-drug antibodies (CIS 2024) - "At 260 weeks, at adose of 0.37 mg/kg/week divided thrice weekly, plasma ADA activity was52.47 umol/h/ml and RBC %dAXP was 0.5%.Anti-drug antibodies in patients treated with PEG-ADA are usually nonneutralizing; in this case neutralizing antibodies were identified as theefficacy of ERT diminished. Through significant increases in elapegademase-lvlr dose and frequency, therapeutic efficacy was restored withoutimmunosuppressive agents."

Clinical • Dermatology • Genetic Disorders • Immunology • Primary Immunodeficiency

Multi-Year Registry Study of Elapegademase-lvlr Treatment in Patientswith Adenosine Deaminase Severe Combined Immunodeficiency (ADASCID) Requiring Enzyme Replacement Therapy (ERT) (CIS 2024) - "However, due to concerns with thesafety and stability, Adagen® was replaced in 2018 by Revcovi® (elapegademase-lvlr), a PEGylated recombinant ADA. In this registry study, effectiveness of elapegademase-lvlr wasmaintained for up to 4 years of use."

Clinical • Bone Marrow Transplantation • Genetic Disorders • Immunology • Infectious Disease • Primary Immunodeficiency • Transplantation

Treatment with Elapegademase Restores Immunity in Infants with Adenosine Deaminase Deficient Severe Combined Immunodeficiency. (PubMed, J Clin Immunol) - "Revcovi 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."

Journal • Bone Marrow Transplantation • Cardiovascular • Gene Therapies • Genetic Disorders • Hematological Disorders • Immunology • Primary Immunodeficiency • Thrombocytosis • Transplantation

ADA Deficiency: Improvement in Immune System after Enzyme Replacement Therapy (ACAAI 2023) - "She was placed in positive pressure isolation and given antimicrobial prophylaxis with acyclovir, fluconazole and trimethoprim-sulfamethoxazole. Elapegademase-lvlr treatment was initiated...Our patient showed clinical and immunological improvement from ERT. ERT should be considered in ADA SICD patients while awaiting definitive curative treatment."

Gene Therapies • Genetic Disorders • Hematological Disorders • Immunology • Otorhinolaryngology • Primary Immunodeficiency • CD4 • CD8

Safety and efficacy of elapegademase in patients with adenosine deaminase deficiency: A multicenter, open-label, single-arm, phase 3, and postmarketing clinical study. (PubMed, Immun Inflamm Dis) - "This study showed that elapegademase had comparable safety and efficacy to pegademase as ERT for ADA deficiency by demonstrating stable maintenance of sufficient ADA activity and lowering dAXP to undetectable levels, while no drug-related adverse events were reported (Trial registration: JapicCTI-163204)."

Journal • P3 data • P4 data • Review • Cytomegalovirus Infection • Genetic Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Metabolic Disorders • Pneumonia • Primary Immunodeficiency • Respiratory Diseases

Late onset ADA deficiency presenting with recurrent encephalitis (EAACI 2023) - "With the diagnosis of late-onset ADA deficiency, elapegademase-lvl was started twice a week and regular IVIG therapy...Conclusion ADA deficiency should be kept in mind in the differential diagnosis of patients presenting with recurrent infections and neurologic findings. Regular monitoring of toxic metabolite levels of patients treated wth enzyme replacement is mandatory."

Late-breaking abstract • Immunology • Primary Immunodeficiency

Early immune reconstitution in an infant with adenosine deaminase deficient severe combined immunodeficiency started on enzyme replacement therapy (CIS 2023) - "Enzyme Replacement Therapy with Elapegademase-IvIr is typically used as a bridge prior to undergoing definitive treatment with HSCT or HSC-GT...Download : Download high-res image (94KB) Download : Download full-size image Figure 1 . Download : Download high-res image (61KB) Download : Download full-size image Figure 2 ."

Bone Marrow Transplantation • Genetic Disorders • Immunology • Primary Immunodeficiency

Corporate Lunch Symposium: Safety and Efficacy of PEGylated Recombinant Adenosine Deaminase in ADA-SCID: Results from the first-in-human phase 3 study (CIS 2023) - "Sponsored by Chiesi"

Clinical • P1 data • P3 data

Registry Study of Revcovi Treatment in Patients With ADA-SCID (clinicaltrials.gov) - P=N/A | N=32 | Completed | Sponsor: Chiesi Farmaceutici S.p.A. | Recruiting ➔ Completed | Trial completion date: Sep 2023 ➔ Jan 2023

Trial completion • Trial completion date • Genetic Disorders • Immunology • Primary Immunodeficiency

Long-term immune reconstitution in ADA-deficient patients treated with elapegademase: a real-world experience. (PubMed, J Allergy Clin Immunol Pract) - "REVCOVI® is effective for the management of ADA-SCID."

Journal • Real-world • Real-world evidence • Genetic Disorders • Immunology • Primary Immunodeficiency • CD19 • CD4

PEGylated Recombinant Adenosine Deaminase Maintains Detoxification and Lymphocyte Counts in Patients with ADA-SCID. (PubMed, J Clin Immunol) - "Elapegademase 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."

Journal • Genetic Disorders • Immunology • Pain • Primary Immunodeficiency

Registry Study of Revcovi Treatment in Patients With ADA-SCID (clinicaltrials.gov) - P=N/A | N=34 | Recruiting | Sponsor: Chiesi Farmaceutici S.p.A. | N=20 ➔ 34 | Trial primary completion date: Jun 2023 ➔ Jan 2023

Enrollment change • Trial primary completion date • Genetic Disorders • Immunology • Primary Immunodeficiency

A young child with ADA-SCID and Glutaric acidemia type -1 maintained on Elapegademase (AAAAI 2022) - "Here, we describe a boy from the Amish community who was diagnosed with both conditions, managed on ERT, prophylactic therapies, and a specialized diet until risk of metabolic crises subsided. He is currently doing well and awaiting transplant evaluation."

Clinical • Bone Marrow Transplantation • Cardiovascular • CNS Disorders • Dystonia • Gene Therapies • Genetic Disorders • Immunology • Infectious Disease • Movement Disorders • Primary Immunodeficiency • Transplantation

Comparison of elapegademase and pegademase in ADA-deficient patients and mice. (PubMed, Clin Exp Immunol) - "ELA-ADA has similar in vitro and possibly better in vivo activity than ADAGEN. Future studies will determine whether ELA-ADA results in improved long-term immune reconstitution."

Journal • Genetic Disorders • Immunology • Primary Immunodeficiency

Registry Study of Revcovi Treatment in Patients With ADA-SCID (clinicaltrials.gov) - P=N/A; N=20; Recruiting; Sponsor: Leadiant Biosciences, Inc.; Not yet recruiting ➔ Recruiting

Enrollment open

Dysregulated IL-6 Dependent Dermal Adenosine Signaling via Adenosine A2A Receptor May Drive Fibrosis in Systemic Sclerosis (ACR-ARHP 2019) - "Production of key profibrotic mediators (collagen α1[Col1], alpha smooth muscle actin [αSMA] and connective tissue growth factor [CTGF]) was analysed by western blot of cell lysates in response to adenosine receptor agonist 5’-N-ethylcarboxamidoadenosine (NECA), A2A adenosine agonist (CGS-21680), A2A adenosine antagonist (ZM241385) and polyethylene glycol conjugated recombinant bovine ADA[PEG-rADA] (EZN 2279- elapegademase). These data suggest adenosinergic signalling is profibrotic and altered in SSc and that an ADORA2A-IL6 dependent loop may contribute to fibrosis. This may have therapeutic relevance for SSc."

EZN-2279 in Patients With ADA-SCID (clinicaltrials.gov) - P3; N=6; Completed; Sponsor: Leadiant Biosciences, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Sep 2019 ➔ May 2019; Trial primary completion date: Sep 2019 ➔ May 2019

Clinical • Trial completion • Trial completion date • Trial primary completion date

Revcovi, Japan’s first drug for ADA deficiency, receives marketing approval (Teijin Press Release) - "Teijin Pharma Limited...announced today that it has acquired marketing approval for Revcovi 2.4 mg for intramuscular injection [Elapegademase (genetical recombination)] from the Ministry of Health, Labor and Welfare (MHLW)....In a Phase III trial conducted by Teijin Pharma in Japan and a Phase III trial conducted by Leadiant Biosciences, Inc. in the United States, Revcovi injection increased ADA activity and suggested improvement in immune function."

Japanese regulatory

Registry Study of Revcovi Treatment in Patients With ADA-SCID (clinicaltrials.gov) - P; N=20; Not yet recruiting; Sponsor: Leadiant Biosciences, Inc.

Clinical • New trial

Treatment of Adenosine Deaminase Severe Combined Immunodeficiency with Pegylated Recombinant Adenosine Deaminase. a Clinical Trial of Patients Transitioned from Pegademase to Elapegademase-lvlr (CIS 2019) - "Introduction: Accumulation of intracellular adenosine and deoxyadenosine nucleotides (dAXP) due to adenosine deaminase J Clin Immunol deficiency results in profound lymphopenia and severe combined immunodeficiency. Revcovi appears safe in ADA-SCID patients, provides adequate detoxification (dAXP<0.02mmol/L) and sustained trough plasma ADA activity at ~ 2X trough activity provided by Adagen with improved lymphocyte counts. Revcovi received FDA approval for treatment of ADA-SCID on 10/5/18."

Clinical

EZN-2279 in Patients With ADA-SCID (clinicaltrials.gov) - P3; N=6; Active, not recruiting; Sponsor: Leadiant Biosciences, Inc.; Trial completion date: Mar 2019 ➔ Sep 2019; Trial primary completion date: May 2018 ➔ Sep 2019; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Trial completion date • Trial primary completion date