Multi-Year Registry Study of Elapegademase Treatment in Patients With Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) Requiring Enzyme Replacement Therapy.
Morna J Dorsey, Manish J Butte, Jay A Lieberman, Heather Lehman, Tracy Fausnight, Michael D Keller, Caroline Fradette, Michael S Hershfield, Tamara C Pozos, Anna Rozova, Luke A Wall, Jeffrey J Bednarski, Teresa K Tarrant, Hey J Chong, Bob Geng, Noemi Toiber Temin, Susan S Laubach, Leo Lin, Talal Mousallem, Jolan E Walter
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引用次数: 0
Abstract
Purpose: The safety and tolerability of elapegademase (elapegademase-lvlr; Revcovi®) a PEGylated recombinant adenosine deaminase (ADA), were demonstrated in two Phase 3 clinical trials in the U.S. and Japan in patients with ADA-deficient severe combined immunodeficiency (ADA-SCID). Elapegademase replaced Adagen® (pegademase, a PEGylated bovine ADA) in 2018. This registry study (NCT03878069) was conducted as a post-marketing requirement to bolster the limited safety and effectiveness data on elapegademase in patients with ADA-SCID and to study patients starting on enzyme replacement therapy (ERT) de novo.
Methods: Patients were managed by routine clinical care and treating physicians' judgement from September 2019 to January 2023. Primary endpoints included trough plasma ADA activity and total trough erythrocyte deoxyadenosine nucleotides (dAXP). Secondary outcomes included lymphocyte counts, hospitalizations, infections, and safety outcomes.
Results: Thirty-two patients were grouped as ERT-naïve (n = 7; infants and children with no prior ERT [EN]); pegademase-transitioning (n = 21; from pegademase to elapegademase [PT]); and patients who had participated in the Phase 3 clinical trial (n = 4; STP-2279-002; [STP]). The EN group maintained optimal plasma ADA activity, increased lymphocyte counts, had manageable infections, and had no mortality for up to 30 months while on elapegademase. The STP group and 66.7% of the PT group continued to maintain satisfactory levels of both ADA and dAXP with stable rates of infections and hospitalizations and stable lymphocyte counts for up to 48.6 months. Variability on all measures was seen, but overall, patients did not deteriorate while on elapegademase.
Conclusion: Effectiveness of elapegademase was maintained up to 4 years of use and with no new safety concerns.
期刊介绍：
The Journal of Clinical Immunology publishes impactful papers in the realm of human immunology, delving into the diagnosis, pathogenesis, prognosis, or treatment of human diseases. The journal places particular emphasis on primary immunodeficiencies and related diseases, encompassing inborn errors of immunity in a broad sense, their underlying genotypes, and diverse phenotypes. These phenotypes include infection, malignancy, allergy, auto-inflammation, and autoimmunity. We welcome a broad spectrum of studies in this domain, spanning genetic discovery, clinical description, immunologic assessment, diagnostic approaches, prognosis evaluation, and treatment interventions. Case reports are considered if they are genuinely original and accompanied by a concise review of the relevant medical literature, illustrating how the novel case study advances the field. The instructions to authors provide detailed guidance on the four categories of papers accepted by the journal.
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