REVCOVI Solution for injection Ref.[10276] Active ingredients: Elapegademase

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.

Adagen-naïve patients

The starting weekly dose of REVCOVI is 0.4 mg/kg based on ideal body weight or actual weight whichever is greater, 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 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.

2.2 Administration Instructions

REVCOVI is for IM injection only. 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.

Preparation of Injection and Procedure Instructions:

• REVCOVI should not be diluted nor mixed with any other drug prior to administration.
• Visually inspect REVCOVI for particulate matter and discoloration prior to administration. REVCOVI is a clear, colorless solution; discard if solution is discolored, cloudy or contains particulate matter.
• Do not freeze or shake. REVCOVI should not be used if there are any indications that it may have been frozen. Once removed from refrigeration, allow REVCOVI to equilibrate to room temperature for 30 minutes.
• REVCOVI is to be administered using polypropylene syringes. Draw the solution from the vial with a 25- gauge needle or larger.
• Change the needle to a size and gauge appropriate for the patient’s intramuscular administration.
• REVCOVI should be administered immediately after syringe preparation.
• Any remaining medication in the vial must be discarded immediately.

2.3 Therapeutic Monitoring Schedule

The treatment of ADA-SCID with REVCOVI should be monitored by measuring trough plasma ADA activity, trough 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.

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

ADA Activity

Once treatment with REVCOVI has been initiated, a target trough plasma ADA activity should be at least 30 mmol/hr/L. In order to determine an effective dose of REVCOVI, trough plasma ADA activity (pre-injection) should be determined every 2 weeks for Adagen-naïve patients and every 4 weeks for patients previously receiving Adagen therapy, during the first 8-12 weeks of treatment, and every 3-6 months thereafter.

A decrease of ADA activity below this level suggests noncompliance to treatment or a development of antibodies (anti-drug, anti-PEG, and neutralizing antibodies). Antibodies to REVCOVI should be suspected if a persistent fall in pre-injection levels of trough plasma ADA activity below 15 mmol/hr/L occurs. In such patients, testing for antibodies to REVCOVI should be performed.

If a persistent decline in trough plasma ADA activity occurs, immune function and clinical status should be monitored closely and precautions should be taken to minimize the risk of infection. If antibodies to REVCOVI are found to be the cause of a persistent fall in trough plasma ADA activity, then adjustment in the dosage of REVCOVI and other measures may be taken to induce tolerance and restore adequate ADA activity.

Erythrocyte dAXP

Two months after starting REVCOVI treatment, trough erythrocyte dAXP levels should be maintained below 0.02 mmol/L, and monitored at least twice a year.

Immune Function

The degree of immune function may vary from patient to patient. Each patient will require appropriate monitoring consistent with immunologic status. Total and subset lymphocytes should be monitored periodically as follows:

• Adagen-naïve patients: every 4–8 weeks for up to 1 year, and every 3–6 months thereafter
• Other patients: every 3-6 months

Immune 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.

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).

Store REVCOVI in the refrigerator between 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze or shake. REVCOVI should not be used if there are any indications that it may have been frozen.