Elapegademase-lvlr (Monograph)

Brand name: Revcovi
Drug class: Enzymes
Chemical name: Poly(oxy-1,2-ethanediyl), α-carboxy-ω-methoxy-, amide with adenosine deaminase (synthetic)
Molecular formula: C₁₇₉₇H₂₇₉₅N₄₇₇O₅₄₄S₁₂
CAS number: 1709806-75-6

Introduction

Elapegademase-lvlr is an enzyme.

Uses for Elapegademase-lvlr

Elapegademase-lvlr has the following uses:

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

Elapegademase-lvlr Dosage and Administration

General

Elapegademase-lvlr is available in the following dosage form(s) and strength(s):

Injection: 2.4 mg/1.5 mL (1.6 mg/mL) in a single-dose vial.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

• The treatment of ADA-SCID with elapegademase-lvlr should be monitored by measuring trough plasma adenosine deaminase (ADA) activity, trough deoxyadenosine nucleotide (dAXP) levels, and/or total lymphocyte counts. Monitoring should be more frequent if therapy was interrupted or if an enhanced rate of clearance of plasma ADA activity develops. See full prescribing information for specific instructions on therapeutic drug monitoring of elapegademase-lvlr, including target trough ADA activity and dAXP levels and recommended monitoring schedules.

• Collect blood samples for the analysis of trough plasma ADA activity and trough dAXP level prior to the first administration of elapegademase-lvlr for the week.

Pediatric Patients

Elapegademase-lvlr is for intramuscular (IM) injection only. See full prescribing information for specific instructions on preparation and administration of the IM injection. Follow sterile IM administration technique guidelines appropriate to the patient’s age and anatomy (i.e., choice of needle gauge and length, site of administration). Take precautions not to inject into or near an artery or nerve. Alternate the injection site periodically.

Patients transitioning from Adagen (pegademase bovine) to elapegademase-lvlr:

If a patient’s weekly Adagen dose is unknown, or a patient’s weekly Adagen dose is at or lower than 30 units/kg, the recommended minimum starting dose of elapegademase-lvlr is 0.2 mg/kg, intramuscularly, once a week.

If a patient’s weekly Adagen dose is above 30 units/kg, an equivalent weekly elapegademase-lvlr dose (mg/kg) should be calculated using the following conversion formula:

elapegademase-lvlr dose in mg/kg = pegademase bovine dose (in units/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 dAXP levels 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 IM administrations during a week.

Adagen (pegademase bovine)-naïve patients:

The starting weekly dose of elapegademase-lvlr is 0.4 mg/kg based on ideal body weight, divided into two doses (0.2 mg/kg twice a week), intramuscularly, for a minimum of 12 to 24 weeks until immune reconstitution is achieved. After that, the dose may be gradually adjusted down to maintain trough ADA activity over 30 mmol/hr/L, trough dAXP level under 0.02 mmol/L, and/or to maintain adequate immune reconstitution based on clinical assessment of the patient.

The optimal long-term dose and schedule of administration should be established by the treating physician for each patient individually and may be adjusted based on the laboratory values for trough ADA activity, trough dAXP level, and/or on the treating physician’s medical assessment of the patient’s clinical status.

Adults

Elapegademase-lvlr is for IM injection only. See full prescribing information for specific instructions on preparation and administration of the IM injection. Follow sterile IM administration technique guidelines appropriate to the patient’s age and anatomy (i.e., choice of needle gauge and length, site of administration). Take precautions not to inject into or near an artery or nerve. Alternate the injection site periodically.

Patients transitioning from Adagen (pegademase bovine) to elapegademase-lvlr:

If a patient’s weekly Adagen dose is unknown, or a patient’s weekly Adagen dose is at or lower than 30 units/kg, the recommended minimum starting dose of elapegademase-lvlr is 0.2 mg/kg, intramuscularly, once a week.

If a patient’s weekly Adagen dose is above 30 units/kg, an equivalent weekly elapegademase-lvlr dose (mg/kg) should be calculated using the following conversion formula:

elapegademase-lvlr dose in mg/kg = pegademase bovine dose (in units/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 dAXP levels 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 IM administrations during a week.

Adagen (pegademase bovine)-naïve patients:

The starting weekly dose of elapegademase-lvlr is 0.4 mg/kg based on ideal body weight, divided into two doses (0.2 mg/kg twice a week), intramuscularly, for a minimum of 12 to 24 weeks until immune reconstitution is achieved. After that, the dose may be gradually adjusted down to maintain trough ADA activity over 30 mmol/hr/L, trough dAXP level under 0.02 mmol/L, and/or to maintain adequate immune reconstitution based on clinical assessment of the patient.

The optimal long-term dose and schedule of administration should be established by the treating physician for each patient individually and may be adjusted based on the laboratory values for trough ADA activity, trough dAXP level, and/or on the treating physician’s medical assessment of the patient’s clinical status.

Related/similar drugs

Revcovi, elapegademase

Cautions for Elapegademase-lvlr

Contraindications

None

Warnings/Precautions

Injection Site Bleeding in Patients with Thrombocytopenia

Since elapegademase-lvlr is administered by IM injection, it should be used with caution in patients with thrombocytopenia and should not be used if thrombocytopenia is severe.

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.

Specific Populations

Pregnancy

Risk Summary: Adequate and well-controlled studies with elapegademase-lvlr have not been conducted in pregnant women to inform a drug-associated risk. Animal reproduction studies have not been conducted with elapegademase-lvlr. It is not known whether elapegademase-lvlr 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.

Human Data: No pregnancy was reported for any patients receiving elapegademase-lvlr. There are two reports of confirmed cases of successful pregnancy and delivery in ADA-SCID patients treated with Adagen (pegademase bovine; 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 elapegademase-lvlr, more frequent monitoring of the health status for both the mother during pregnancy and the development of the offspring is recommended.

Lactation

Risk Summary: Human or animal lactation studies have not been conducted to assess the presence of elapegademase-lvlr in breast milk, the effects on the breastfed infant, or the effects on milk production for the mother. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for elapegademase-lvlr and any potential adverse effects on the breastfed infant from elapegademase-lvlr or from the underlying maternal condition.

Pediatric Use

The safety and efficacy of elapegademase-lvlr have been established in pediatric patients.

Geriatric Use

Elapegademase-lvlr was not studied in patients 65 years and older.

Common Adverse Effects

The most common adverse reactions reported were cough (50%) and vomiting (33%).

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

The drug interaction potential of elapegademase-lvlr is not known.

Actions

Mechanism of Action

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. Maintaining a low level of 2'-deoxyadenosine and adenosine is crucial for proper number and function of immune cells as well as decreasing the frequency of opportunistic infections. Elevated adenosine levels, as occurring in ADA deficiency, contribute to apoptosis and a block in the differentiation of thymocytes, causing severe T-lymphopenia.

Elapegademase-lvlr provides an exogenous source of ADA enzyme that is associated with a decrease in toxic adenosine and deoxyadenosine nucleotides levels as well as an increase in lymphocyte number.

Advice to Patients

Patient Counseling Information

Counsel patients and caregivers that continuous therapy and adherence to the recommended drug schedule is important for the success of the treatment.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• What condition is Revcovi used to treat?

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