Long-Term Immune Reconstitution in ADA-Deficient Patients Treated With Elapegademase: A Real-World Experience

Abstract

ADAGEN®, a bovine-based enzyme replacement therapy (ERT) has been used to treat adenosine deaminase severe combined immune deficiency (ADA-SCID). In 2018, ADAGEN® was replaced by REVCOVI®, (elapegademase) a modified bovine recombinant protein. To determine the real-life long-term benefits of REVCOVI® in ADA- SCID. Data on ERT, infectious and non-infectious complications, and metabolic and immune evaluations were collected from 17 ADA-SCID treated for 6 months or more with REVCOVI®. Eleven patients had previously received ADAGEN® for 16 to 324 months while 6 patients were ERT-naïve. REVCOVI® was administered twice weekly at 0.4 mg/kg/week in ERT-naïve, while patients transitioning to REVCOVI® from ADAGEN® typically continued at the same frequency and equivalent dosing as ADAGEN®, resulting in significantly lower (p=0.007) total REVCOVI® dose in the transitioning group. REVCOVI® treatment in ERT-naïve group led to the resolution of many clinical and laboratory complications of ADA deficiency, while among the transitioning patients there were no new adverse effects. REVCOVI® treatment increased plasma ADA activity and decreased dAXP among most patients, effects that persisted throughout the 7-37 months treatment periods, except in 2 patients with incomplete adherence. Among some patients, after 0.5 to 6 months, injection frequency was reduced to once a week, while maintaining adequate metabolic profiles. All ERT-naïve infants treated with REVCOVI® demonstrated increased CD4+ T and CD19+ B cell numbers, although in most transitioning patients these counts remained stable but lower than normal. REVCOVI® is effective for the management of ADA-SCID.