REVCOVI EFFICACY WAS PROVEN IN A US TRIAL
US study description: Phase III, open-label, multicenter, single arm, one-way crossover study to evaluate the safety, efficacy, and pharmacokinetics of Revcovi in 6 US patients with ADA-SCID who were receiving therapy with Adagen® (pegademase bovine), a legacy enzyme replacement therapy (ERT) that is no longer available for use.1 The study consisted of 3 phases1:
| Adagen Lead-in At least 3 weeks |
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| Revcovi Treatment Weeks 1-21 |
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| Maintenance Weeks 21+ |
| Adagen Lead-in At least 3 weeks |
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Revcovi Treatment Weeks 1-21 |
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Maintenance Weeks 21+ |
The starting weekly dose of Revcovi was calculated based on the last Adagen dose received in the study1. Weekly Revcovi doses ranged from 0.188 mg/kg to 0.292 mg/kg.1
STUDY ENDPOINTS1
See the endpoints below for interim results:
Primary endpoint: Detoxification through Week 21.a Most patients achieved metabolic detoxification with Revcovi1
- Five patients (5/6) reached the protocol-defined 21-week primary endpoint of trough dAXP levels ≤0.02 mmol/L1
- Three patients (3/6) receiving Revcovi for over 135 weeks achieved metabolic detoxification at most tested time points1
- The other 3 patients in the study also achieved complete detoxification based on dAXP level1
Secondary endpoint: Plasma ADA activity.b All patients experienced improved ADA activity with Revcovi1
- All 3 patients (3/6) receiving Revcovi for at least 135 weeks achieved trough plasma ADA activity ≥30 mmol/hr/L1
Secondary endpoint: Immune status.c Lymphocyte counts improved in some patients receiving Revcovi1
For the 3 patients (3/6) receiving Revcovi for at least 135 weeks:
- Total lymphocyte counts and B-, T-, and natural killer (NK)-lymphocyte subset counts during Revcovi treatment increased above Adagen levels observed during the lead-in phase1
- Maximum increases were approximately 3-fold at Weeks 60-73 for one patient, 2- to 3-fold at Weeks 73-99 for one patient, and 1.5- to 3-fold for the third patient at several time points.1,d The other 3 patients in the study also showed stable or slightly increased lymphocyte counts with Revcovi as compared to the Adagen lead-in phase1,d
A JAPANESE MULTICENTER TRIAL OF 4 PATIENTS SHOWED SIMILAR IMPROVEMENTS IN ADA ACTIVITY LEVELS, dAXP CONCENTRATION, AND TOTAL LYMPHOCYTE COUNTS.1
REVCOVI SAFETY PROFILE
- The most commonly reported adverse events (AEs) in the US study were cough and vomiting1
- In the Japanese study, the most common AEs were respiratory infections. One infant who had cytomegalovirus (CMV) pneumonitis at study entry died of CMV disease at 16 weeks1
- In the US study, no unexpected AEs were observed compared to patients treated with Adagen1
- As with all therapeutic proteins, there is potential for immunogenicity. The immunogenicity results from Study 1 and Study 2 suggest that patients who previously received Adagen may present an immunologic response to Revcovi. Therefore, monitoring for changes in ADA levels during Revcovi treatment is recommended1
aTrough erythrocyte dAXP levels <0.02 mmol/L.
bAt or above 15 mmol/hr/L.
cTotal lymphocyte and T-, B-, and NK-lymphocyte subset counts.
dImmune function, including the ability to produce antibodies, generally improves after 2-6 months of therapy and matures over a longer period. In general, there is a lag between the correction of the metabolic abnormalities and improved immune function. Improvement in the general clinical status of the patient may be gradual (as evidenced by improvement in various clinical parameters) but should be apparent by the end of the first year of therapy.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
- Injection site bleeding in patients with thrombocytopenia: Increased risk of local bleeding in patients with thrombocytopenia; should not be used if thrombocytopenia is severe.
- Delay in improvement of immune function: Protect immune deficient patients from infections until improvement in immune function.
ADVERSE REACTIONS
The most commonly reported adverse reactions were cough (50%) and vomiting (33%).
In addition, the following post-marketing reports for the same class of enzyme replacement therapy used in the treatment of ADA-SCID may also be seen with Revcovi treatment:
- Hematologic events: hemolytic anemia, autoimmune hemolytic anemia, thrombocythemia, thrombocytopenia and autoimmune thrombocytopenia
- Dermatological events: injection site erythema, urticaria
- Lymphomas
IMPORTANT MONITORING INFORMATION
Treatment with Revcovi should be monitored by measuring trough plasma ADA activity and trough dAXP levels for maintenance of therapeutic targets. If a persistent decline in plasma ADA activity occurs, immune function and clinical status should be monitored closely, and precautions should be taken to minimize the risk of infection.
INDICATION
Revcovi® (elapegademase-lvlr) is indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.
Please see the Full Prescribing Information.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
- Injection site bleeding in patients with thrombocytopenia: Increased risk of local bleeding in patients with thrombocytopenia; should not be used if thrombocytopenia is severe.
- Delay in improvement of immune function: Protect immune deficient patients from infections until improvement in immune function.
ADVERSE REACTIONS
The most commonly reported adverse reactions were cough (50%) and vomiting (33%).
In addition, the following post-marketing reports for the same class of enzyme replacement therapy used in the treatment of ADA-SCID may also be seen with Revcovi treatment:
- Hematologic events: hemolytic anemia, autoimmune hemolytic anemia, thrombocythemia, thrombocytopenia and autoimmune thrombocytopenia
- Dermatological events: injection site erythema, urticaria
- Lymphomas
IMPORTANT MONITORING INFORMATION
Treatment with Revcovi should be monitored by measuring trough plasma ADA activity and trough dAXP levels for maintenance of therapeutic targets. If a persistent decline in plasma ADA activity occurs, immune function and clinical status should be monitored closely, and precautions should be taken to minimize the risk of infection.
INDICATION
Revcovi® (elapegademase-lvlr) is indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.
Please see the Full Prescribing Information.
- Revcovi. Prescribing information. Chiesi USA, Inc.; 2021.
Revcovi Efficacy & Safety Data