ASPAVELI Solution for infusion Ref.[49950] Active ingredients: Pegcetacoplan

Source: European Medicines Agency (EU)  Revision Year: 2026  Publisher: Swedish Orphan Biovitrum AB (publ), SE-112 76 Stockholm, Sweden

4.1. Therapeutic indications

ASPAVELI is indicated as monotherapy in the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who have haemolytic anaemia.

ASPAVELI is indicated for the treatment of adult and adolescent patients aged 12 to 17 years with C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN) in combination with a renin-angiotensin system (RAS) inhibitor, unless RAS inhibitor treatment is not tolerated or contraindicated.

4.2. Posology and method of administration

Therapy should be initiated under the supervision of a healthcare professional experienced in the management of patients with haematological or renal disorders. Self-administration and home infusion should be considered for patients who have tolerated treatment well in experienced treatment centres. The decision of a possibility of self-administration and home infusions should be made after evaluation and recommendation from the treating physician.

Posology

Pegcetacoplan can be given by a healthcare professional or administered by the patient or caregiver following proper instruction.

PNH

Adult patients with PNH

Pegcetacoplan is administered twice weekly as a 1 080 mg subcutaneous infusion with a commercially available syringe system infusion pump or on-body delivery system, that can deliver doses up to 20 mL. The twice weekly dose should be administered on Day 1 and Day 4 of each treatment week.

PNH is a chronic disease and treatment with ASPAVELI is recommended to continue for the patient's lifetime, unless the discontinuation of this medicinal product is clinically indicated (see section 4.4).

Patients with PNH switching to ASPAVELI from a C5 inhibitor

For the first 4 weeks, pegcetacoplan is administered as twice weekly subcutaneous doses of 1 080 mg in addition to the patient's current dose of C5 inhibitor treatment to minimise the risk of haemolysis with abrupt treatment discontinuation. After 4 weeks, the patient should discontinue C5 inhibitor before continuing on monotherapy with ASPAVELI.

Switches from complement inhibitors other than eculizumab have not been studied. Discontinuing other complement inhibitors before reaching steady-state of pegcetacoplan should be done with caution (see section 5.2).

Dose adjustment in PNH

The dosing regimen may be changed to 1 080 mg every third day (e.g., Day 1, Day 4, Day 7, Day 10, Day 13, and so forth) if a patient has a lactate dehydrogenase (LDH) level greater than 2 x upper limit of normal (ULN). In the event of a dose increase, LDH should be monitored twice weekly for at least 4 weeks (see section 4.4).

C3G and primary IC-MPGN

Pegcetacoplan is administered twice weekly as a subcutaneous infusion with a commercially available syringe system infusion pump or on-body delivery system, that can deliver doses up to 20 mL. The twice weekly dose should be administered on Day 1 and Day 4 of each treatment week.

C3G and primary IC-MPGN are chronic diseases. Discontinuation of this medicinal product is not recommended unless clinically indicated.

Adult patients with C3G or primary IC-MPGN

Pegcetacoplan is administered twice weekly as a 1 080 mg subcutaneous infusion.

Adolescent patients with C3G or primary IC-MPGN

For adolescent patients, the dosing regimen is based on the patient´s body weight and consists of the following:

Body weightFirst dose
(infusion volume)
Second dose
(infusion volume)
Maintenance dose
(infusion volume)
≥50 kg1 080 mg twice weekly (20 mL)
35 to <50 kg648 mg (12 mL)810 mg (15 mL)810 mg twice weekly (15 mL)
30 to <35 kg540 mg (10 mL)540 mg (10 mL)648 mg twice weekly (12 mL)

Missed dose

If a dose of pegcetacoplan for treatment of PNH, C3G or primary IC-MPGN is missed, it should be administered as soon as possible, then the regular schedule should be resumed even if this results in an interval of less than 3 days between the replacement dose and the subsequent dose.

Patients with post-transplant recurrent C3G or primary IC-MPGN

Diagnosis of post-transplant recurrent C3G or primary IC-MPGN should be made based on a renal allograft biopsy. C3G or primary IC-MPGN recurrence may be detected in a routine post-transplant biopsy; otherwise, a biopsy should be performed when clinical signs indicate recurrent disease. As done in study APL2-C3G-204 (see section 5.1), treatment with pegcetacoplan can be started before the onset of clinical signs such as estimated glomerular filtration rate (eGFR) decrease or urine to protein-to-creatine ratio (uPCR) increase. There is limited experience with the use of pegcetacoplan in patients with recurrent C3G or primary IC-MPGN after transplantation in clinical studies (see section 5.1).

Special populations

Elderly

Although there were no apparent age-related differences observed in clinical studies, the number of patients aged 65 and over is not sufficient to determine whether they respond differently from younger patients. There is no evidence indicating any special precautions are required for treating an elderly population.

Renal impairment

Severe renal impairment (creatinine clearance <30 mL/min) had no effect on the pharmacokinetics (PK) of pegcetacoplan; therefore, pegcetacoplan dose adjustment in patients with renal impairment is not necessary. There are no data available for the use of pegcetacoplan in patients with end-stage renal disease (ESRD) requiring dialysis (see section 5.2).

Hepatic impairment

The safety and efficacy of pegcetacoplan have not been studied in patients with hepatic impairment; however, no dose adjustment is recommended, as hepatic impairment is not expected to impact clearance of pegcetacoplan.

Paediatric population

The safety and efficacy of ASPAVELI in children with PNH aged 0 to <18 years have not yet been established. No data are available.

The safety and efficacy of ASPAVELI in children with C3G or primary IC-MPGN aged below 12 years have not been established. No data are available.

This medicinal product should not be used in children <12 years of age, as non-clinical safety data are not available for this age group.

Method of administration

ASPAVELI should only be administered via subcutaneous administration using a commercially available syringe system infusion pump or on-body delivery system.

This medicinal product can be self-administered. When self-administration is initiated, the patient will be instructed by a qualified healthcare professional in infusion techniques, the use of a syringe system infusion pump or an on-body delivery system, the keeping of a treatment record, the recognition of possible adverse reactions, and measures to be taken in case these occur.

  • When using a syringe system infusion pump, ASPAVELI should be infused in the abdomen, thighs, hips, or upper arms. Infusion sites should be at least 7.5 cm apart from each other. The infusion sites should be rotated between administrations. The infusion time is approximately 30 minutes (if using two sites) or approximately 60 minutes (if using one site).
  • When using an on-body delivery system, ASPAVELI should be infused at a site on the abdomen. The infusion site should be rotated between administrations following the device manufacturer's instructions. The infusion time varies by patient and typically ranges from 30 to 60 minutes.

Infusion into areas where the skin is tender, bruised, red, or hard should be avoided. Infusion into tattoos, scars, or stretch marks should be avoided. The infusion should be started promptly after drawing this medicinal product into the syringe. Administration should be completed within 2 hours after preparing the syringe. For instructions on the preparation and infusion of the medicinal product, see section 6.6.

4.9. Overdose

In the postmarketing setting, cases of overdose have been reported, with no new safety events observed. In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted.

6.3. Shelf life

30 months.

6.4. Special precautions for storage

Store in a refrigerator (2°C–8°C).

Store in the original carton to protect from light.

6.5. Nature and contents of container

A Type I glass vial with a stopper (chlorobutyl or bromobutyl), and a seal (aluminium) with a flip-off cap (polypropylene) containing 54 mg/mL of sterile solution.

Each single pack contains 1 vial.

Multipack containing 8 (8 packs of 1) vials.

Not all pack sizes may be marketed.

6.6. Special precautions for disposal and other handling

ASPAVELI comes as a ready-to-use solution in single-use vials. Because the solution contains no preservative, this medicinal product should be infused immediately after preparing the syringe.

ASPAVELI is a clear, colourless to slightly yellowish aqueous solution. Do not use if the liquid looks cloudy, contains particles, or is dark yellow.

Always bring the vial to the room temperature for approximately 30 minutes before use.

Remove the protective flip cap from the vial to expose the central portion of the gray rubber stopper of the vial. Clean the stopper with a new alcohol wipe and allow the stopper to dry. Do not use if the protective flip cap is missing or damaged.

Preparing the syringe:

Option 1: If using a needleless transfer device (such as a vial adapter), follow the instructions provided by the device manufacturer.

Option 2: If transfer is done using a transfer needle and a syringe, follow the instructions below:

  • Attach a sterile transfer needle to a sterile syringe.
  • Pull back the plunger to fill the syringe with air, which should be about 20 mL.
  • Make sure the vial is in upright position. Do not turn the vial upside down.
  • Push the air-filled syringe with transfer needle attached through the centre of the vial stopper.
  • The tip of the transfer needle should not be in the solution to avoid creating bubbles.
  • Gently push the air from the syringe into the vial. This will inject the air from the syringe into the vial.
  • Invert the vial.
  • With the transfer needle tip in the solution, slowly pull the plunger to fill the syringe with the prescribed dose of ASPAVELI.
  • Remove the filled syringe and the transfer needle from the vial.
  • Do not recap the transfer needle. Unscrew the needle and throw it away in the sharps container.

Administration:

ASPAVELI should only be administered via subcutaneous administration using either a syringe system infusion pump or an on-body delivery system:

  • Follow the device manufacturer's instructions to prepare the infusion pump and tubing. When using an infusion pump, areas for infusion include the abdomen, thighs, hips, or upper arms. Rotate infusion sites from one infusion to the next. If there are multiple infusion sites, they should be at least 7.5 cm apart. The infusion time is approximately 30 minutes (if using two sites) or approximately 60 minutes (if using one site).
  • Follow the device manufacturer's instructions to prepare the on-body delivery system. When using the on-body delivery system, ASPAVELI should be administered at a site on the abdomen. Rotate the infusion site from one infusion to the next. The infusion time varies by patient and typically ranges from 30 to 60 minutes.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

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