Elapegademase

SCID associated with a deficiency of ADA enzyme is a rare, inherited, and often fatal disease. ADA enzyme is involved in purine metabolism, catalyzing the irreversible hydrolytic deamination of adenosine or deoxyadenosine to inosine or deoxyinosine, respectively, as well as several naturally occurring methylated adenosine compounds.

• REVCOVI is indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients. REVCOVI is a recombinant adenosine deaminase indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.

• None.contraindicated

Patients transitioning from Adagen to REVCOVI : The starting dose of REVCOVI is 0.2 mg/kg weekly, intramuscularly. See Full Prescribing Information (FPI) for conversion formula from Adagen to REVCOVI. ( 2.1 ) Adagen-naïve patients : The starting dose of REVCOVI is 0.4 mg/kg weekly based on ideal body weight or actual weight whichever is greater, divided into two doses (0.2 mg/kg twice a week), intramuscularly. ( 2.1 ) For complete information, maintenance dosing and therapeutic monitoring, see FPI. ( 2.1 , 2.3 ) REVCOVI is for intramuscular injection only. See FPI for administration instructions. ( 2.2 ) 2.1 Recommended Dosage Patients transitioning from Adagen to REVCOVI If a patient's weekly Adagen dose is unknown, or a patient's weekly Adagen dose is at or lower than 30 U/kg, the recommended minimum starting dose of REVCOVI is 0.2 mg/kg, intramuscularly, once a week. If a patient's weekly Adagen dose is above 30 U/kg, an equivalent weekly REVCOVI dose (mg/kg) should be calculated using the following conversion formula: REVCOVI dose in mg/kg = Adagen dose in U/kg 150 Subsequent doses may be increased by increments of 0.033 mg/kg weekly if trough ADA activity is under 30 mmol/hr/L, trough deoxyadenosine nucleotides (dAXP) are above 0.02 mmol/L, and/or the immune reconstitution is inadequate based on the clinical assessment of the patient. The total weekly dose may be divided into multiple intramuscular (IM) administrations during a week.

Injection Site Bleeding in Patients with Thrombocytopenia: Increased risk of local bleeding in patients with thrombocytopenia; should not be used if thrombocytopenia is severe. ( 5.1 ) Delay in Improvement of Immune Function: Protect immune deficient patients from infections until improvement in immune function. ( 5.2 ) 5.1 Injection Site Bleeding in Patients with Thrombocytopenia Since REVCOVI is administered by IM injection, it should be used with caution in patients with thrombocytopenia and should not be used if thrombocytopenia is severe. 5.2 Delay in Improvement of Immune Function Maintain precautions to protect immune deficient patients from infections until improvement in immune function has been achieved. The timing and degree of improvement in immune function may vary from patient to patient.

The most common adverse reactions reported were cough (50%) and vomiting (33%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Chiesi USA, Inc. at 1-888-661-9260 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. REVCOVI was administered intramuscularly in two prospective, open-label, single-arm, multi‑center studies to evaluate efficacy, safety, tolerability, and pharmacokinetics in patients with ADA-SCID: Study 1 was performed in the US and Study 2 was performed in Japan [see Clinical Studies ( 14 )] . Overall, 10 patients were treated and adverse reactions reported are summarized below. Study 1 Study 1 is a one-way crossover study, conducted in the US, to evaluate the safety, efficacy, and pharmacokinetics of REVCOVI in patients with ADA‑SCID who were receiving therapy with Adagen. Six patients, 8 to 37 years of age enrolled in the study. Patients' exposure to REVCOVI ranged from 2 weeks to 146 weeks. No deaths were reported and one patient discontinued treatment due to injection site pain associated with an earlier drug product formulation that was consequently modified. The most common adverse reactions were cough (3/6 patients) and vomiting (2/6 patients).

8.1 Pregnancy Risk Summary Adequate and well-controlled studies with REVCOVI have not been conducted in pregnant women to inform a drug-associated risk. Animal reproduction studies have not been conducted with REVCOVI. It is not known whether REVCOVI can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human No pregnancy was reported for any patients receiving REVCOVI. There are two reports of confirmed cases of successful pregnancy and delivery in ADA-SCID patients treated with Adagen (the same class of enzyme replacement therapy used in the treatment of ADA-SCID). No teratogenic effects of Adagen were reported. For patients treated with REVCOVI, more frequent monitoring of the health status for both the mother during pregnancy and the development of the offspring is recommended. 8.2 Lactation Risk Summary Human or animal lactation studies have not been conducted to assess the presence of REVCOVI in breast milk, the effects on the breastfed infant, or the effects on milk production for the mother.

Metabolism

The pharmacokinetics (PK) of REVCOVI were evaluated based on steady state plasma ADA activity in six patients with ADA-SCID (five adults and one pediatric) from two studies (Study 1 and Study 2) who received weekly IM injections at doses ranging from 4.99 to 19.6 mg [see Clinical Studies ( 14 )] . The PK results are summarized in Table 1.

There are no reports of administration of REVCOVI in excess of the prescribed doses. The highest weekly prescribed dose administered in the clinical studies was 0.4 mg/kg. In nonclinical studies, there was no evidence of toxicity related to study drug at doses up to 1.8-fold the clinical dose (based on mean human AUC normalized to the dose of REVCOVI administered per patient), except for a slight increase in activated partial thromboplastin time (APTT).

• Oct 5, 2018BLABLA761092Chiesi Usa Inc

1. 1Nasopharyngitis3713%
2. 2Cough227.5%
3. 3Covid-19227.5%
4. 4Bone Marrow Transplant134.5%
5. 5Sinusitis134.5%
6. 6Weight Decreased124.1%
7. 7Pneumonia113.8%
8. 8Injection Site Pain103.4%
9. 9Pyrexia103.4%
10. 10Rhinorrhoea103.4%
11. 11Off Label Use93.1%
12. 12Diarrhoea82.7%
13. 13Product Dose Omission82.7%
14. 14Rash82.7%
15. 15Weight Increased82.7%

The 1 most recently updated of 1 ClinicalTrials.gov registrations naming Elapegademase as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Registry Study of Revcovi Treatment in Patients With ADA-SCID
  Completed · Observational · 32 enrolled · Chiesi Farmaceutici S.p.A.
  NCT03878069updated 2024-11-15

Frequently asked questions

How does Elapegademase work?

SCID associated with a deficiency of ADA enzyme is a rare, inherited, and often fatal disease. ADA enzyme is involved in purine metabolism, catalyzing the irreversible hydrolytic deamination of adenosine or deoxyadenosine to inosine or deoxyinosine, respectively, as well as several naturally occurring methylated adenosine compounds.

What is Elapegademase used for?

According to FDA labeling, Elapegademase carries indications including: REVCOVI is indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients. REVCOVI is a recombinant adenosine deaminase indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Elapegademase?

Elapegademase is classified as Other immunostimulants, Enzymatic Activity, Increased Lymphocyte Cell Production.

What are the brand names for Elapegademase?

Elapegademase is marketed under brand names including Revcovi.

What are the contraindications for Elapegademase?

Elapegademase labeling lists contraindications including: None.. Always consult the full prescribing information and a clinician.