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. Elapegademase is typically used from diagnosis until hematopoietic stem cell transplant (HSCT) or gene therapy (GT) can be performed, or as a bridge therapy if failed HSCT/GT or continued long term if neither option is feasible. In a phase 3 trial (NCT01420627), patients maintained metabolic detoxification, improved/stabilized lymphocyte counts, and tolerated elapegademase. Given the rarity of ADA-SCID, real-world data are crucial for evaluating its long-term effectiveness and safety.
This analysis included 4 patients from 4 U.S. sites who started elapegademase in the phase 3 trial (January 2014–May 2019) and continued treatment in the U.S. registry (NCT03878069; September 2019–January 2023). All 4 patients received pegademase for 13–24 years before starting elapegademase. Assessments included plasma ADA activity, erythrocyte deoxyadenosine nucleotide (dAXP) levels, and safety outcomes.
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. Mean (range) age at elapegademase initiation was 21 years (16–31 years). Mean (standard deviation) total duration of elapegademase, including in the phase 3 trial, was 69.5 (22.6) months (range, 40.1–95.1 months). At registry end, ADA activity levels were numerically higher than at elapegademase baseline and also exceeded levels at phase 3 trial end. Additionally, all 4 patients were considered metabolically detoxified as satisfactory dAXP levels were maintained (≤ 0.02 mmol/L). Two patients required dose adjustments based on clinical assessments. Three patients experienced eight infections that resolved without sequelae and required no treatment interruption. No patients had any elapegademase-related adverse events.
Patient demographics, baseline characteristics, and primary effectiveness outcomes.
| ADA activity levels (mmol/h/L)a before and during elapegademase treatment | dAXP levels (mmol/L) b before and during elapegademase treatment | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient (ID) | Sex | Age at diagnosis | Pegademase treatment, duration | Age at first elapegademase initiation | Dosing,mg/kg/week | Last data collection | Baseline | At end of phase 3 | At last visit | Baseline | At end of phase 3 | At last visit |
| Race | ||||||||||||
| Ethnicity | ||||||||||||
| 1 | M | 4 months | Pegademase, 18 years | 19 years | 0.08–0.18 | Jan 12, 2023 | 10.9 | 33.74 | 103.76 | <0.002 | 0.010 | 0.007 |
| White | ||||||||||||
| Hispanic or Latino | ||||||||||||
| 2 | F | ∼2 year | Pegademase, 13 years | 16 years | 0.3 | Jan 17, 2023 | 14.26 | 46.17 | 97.66 | <0.002 | 0.008 | 0.004 |
| White | ||||||||||||
| Other | ||||||||||||
| 3 | M | ∼2 months | Pegademase, 17 years | 18 years | 0.17 | Mar 23, 2021 | 12.35 | 36.25 | 65.39 | <0.002 | <0.002 | 0 |
| White | ||||||||||||
| Other | ||||||||||||
| 4 | F | ∼5 years | Pegademase, 24 years | 31 years | 0.26–0.3 | Jan 18, 2023 | 11.33 | 34.55 | 57.6 | <0.002 | <0.002 | 0.003 |
| White | ||||||||||||
| Hispanic or Latino | ||||||||||||
| ADA activity levels (mmol/h/L)a before and during elapegademase treatment | dAXP levels (mmol/L) b before and during elapegademase treatment | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient (ID) | Sex | Age at diagnosis | Pegademase treatment, duration | Age at first elapegademase initiation | Dosing,mg/kg/week | Last data collection | Baseline | At end of phase 3 | At last visit | Baseline | At end of phase 3 | At last visit |
| Race | ||||||||||||
| Ethnicity | ||||||||||||
| 1 | M | 4 months | Pegademase, 18 years | 19 years | 0.08–0.18 | Jan 12, 2023 | 10.9 | 33.74 | 103.76 | <0.002 | 0.010 | 0.007 |
| White | ||||||||||||
| Hispanic or Latino | ||||||||||||
| 2 | F | ∼2 year | Pegademase, 13 years | 16 years | 0.3 | Jan 17, 2023 | 14.26 | 46.17 | 97.66 | <0.002 | 0.008 | 0.004 |
| White | ||||||||||||
| Other | ||||||||||||
| 3 | M | ∼2 months | Pegademase, 17 years | 18 years | 0.17 | Mar 23, 2021 | 12.35 | 36.25 | 65.39 | <0.002 | <0.002 | 0 |
| White | ||||||||||||
| Other | ||||||||||||
| 4 | F | ∼5 years | Pegademase, 24 years | 31 years | 0.26–0.3 | Jan 18, 2023 | 11.33 | 34.55 | 57.6 | <0.002 | <0.002 | 0.003 |
| White | ||||||||||||
| Hispanic or Latino | ||||||||||||
Optimal trough plasma ADA activity was considered to be 30 mmol/h/L or higher.
Detoxified erythrocyte dAXP concentration was defined as 0.02 mmol/L or lower.
Long-term elapegademase was well tolerated with patients achieving stable plasma ADA and dAXP levels and maintaining metabolic detoxification for up to 8 years. This cohort received long duration of ERT for ADA-SCID to date, with up to 30 years of continuous treatment, remaining clinically stable without any new safety concerns.
