Study 1, conducted in the US (NCT 01420627), is an ongoing Phase 3, open-label, multicenter, single-arm, one-way crossover study of REVCOVI. The purpose of this clinical study is to evaluate the safety, efficacy, and PK of REVCOVI in 6 patients with ADA-SCID, 4 males and 2 females, who are receiving therapy with Adagen. The study treatment consists of three phases: Adagen Lead-in Phase (minimum of 3 weeks), the REVCOVI Treatment Phase (weeks 1 through 21), and followed by the REVCOVI Maintenance Phase. Six patients treated in the study were 8 to 37 years of age at the start of the study. The starting weekly dose of REVCOVI was calculated based on the last Adagen dose received in the study. Weekly REVCOVI doses ranged from 0.188 mg/kg to 0.292 mg/kg [see Dosage and Administration (2.1)].

The efficacy endpoints assessed were as follows:

  * Trough dAXP Level (metabolic detoxification was defined as a trough erythrocyte dAXP concentration equal to or below 0.02 mmol/L)
  * Trough plasma ADA activity (adequate trough plasma ADA activity is defined as trough plasma ADA activity equal to or above 15 mmol/hr/L)
  * Immune status (lymphocyte and B-, T-, and NK-lymphocyte subset counts as well as quantitative immunoglobulin [Ig] concentration [IgG, IgA, IgM])



A PK assessment was performed during Week 9 of the REVCOVI Treatment phase [see Clinical Pharmacology (12.3)]. 

Five of six patients reached the 21-week endpoint of the Treatment Phase, and three of six patients received treatment with REVCOVI (elapegademase-lvlr) for over 135 weeks. These patients (except for one value in a patient at Treatment Week 47) had erythrocyte dAXP concentration equal to or below 0.02 mmol/L. These patients had trough plasma ADA activity equal to or above 15 mmol/hr/L at 88/89 timepoints and maintained metabolic detoxification for at least 2 years under REVCOVI treatment. Patients achieved trough plasma ADA activity above 30 mmol/hr/L by week 5, except for one patient who achieved this level at week 1. The mean trough plasma ADA activity for patients receiving REVCOVI at a normalized dose of 0.2 mg/kg/week were 34.3 ± 6.6 mmol/hr/L. The same patients had a mean trough plasma ADA activity of 14.2 ± 5.1 mmol/hr/L when treated with Adagen at a normalized dose of 30 U/kg/week during the Lead-in Phase of the study.

Lymphocyte and subset counts during REVCOVI treatment increased above levels observed during the Adagen Lead-in Phase (i.e., PK day 1 or before the start of REVCOVI treatment): maximum increases of approximately 3-fold at Weeks 60-73 for one patient, maximum increases of approximately 2- to 3-fold at Weeks 73-99 for one patient and approximately 1.5- to 3-fold for the third patient at several timepoints. For these three patients who completed the primary endpoint (21 weeks of treatment) and received REVCOVI for over 135 weeks, a positive trend between high trough plasma ADA activity and increased total lymphocyte counts was observed. 

Observations for the other three patients in the study, indicate that these patients also achieved complete detoxification based on trough dAXP level and trough plasma ADA activity, and show stable or slightly increased lymphocyte counts during REVCOVI treatment relative to values recorded during the Adagen Lead-in Phase.