Crovalimab

Brand Names: Piasky

Drug Class: Complement C5 Inhibitor

Overview

11 DESCRIPTION Crovalimab-akkz, a complement C5 inhibitor, is a humanized monoclonal antibody based on a human IgG1 framework. The recombinant antibody is produced in Chinese hamster ovary CHO cells and consists of two heavy chains (451 amino acid residues each) and two light chains (217 amino acid residues each). The approximate molecular weight is 145 kDa.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Crovalimab-akkz is a monoclonal antibody that specifically binds with high affinity to the complement protein C5, inhibiting its cleavage into C5a and C5b, preventing the formation of the membrane attack complex (MAC). Crovalimab-akkz inhibits terminal complement-mediated intravascular hemolysis in patients with PNH. 12.2 Pharmacodynamics Concentration-dependent inhibition of terminal complement activity following treatment with PIASKY was observed in patients with PNH naïve to complement inhibitor therapy and patients switching from another complement C5 inhibitor therapy.

Indications

  • 1 INDICATIONS AND USAGE PIASKY is indicated for the treatment of adult and pediatric patients 13 years and older with paroxysmal nocturnal hemoglobinuria (PNH) and body weight of at least 40 kg. PIASKY is a complement C5 inhibitor indicated for the treatment of adult and pediatric patients 13 years and older with paroxysmal nocturnal hemoglobinuria (PNH) and body weight of at least 40 kg ( 1 )

Common Doses

  • 000 mg
  • 340 mg
  • 500 mg
  • 680 mg

Dosage

2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for instructions on preparation, dosage, and administration. ( 2.2 , 2.3 , 2.4 , 2.5 ) Start with one loading dose administered by intravenous infusion, followed by 4 additional loading doses administered by subcutaneous injection. Then administer a maintenance dose every 4 weeks by subcutaneous injection. For patients switching from another complement inhibitor, the first loading dose of PIASKY should be administered no sooner than the time of the next scheduled complement inhibitor administration.

Black Box Warning

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS PIASKY, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitidis [see Warnings and Precautions (5.1) ] . Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of PIASKY, unless the risks of delaying therapy with PIASKY...

Contraindications

  • 4 CONTRAINDICATIONS PIASKY is contraindicated: For initiation in patients with an unresolved serious Neisseria meningitidis infection [see Warnings and Precautions (5.1) ]. In patients with a known serious hypersensitivity reaction to crovalimab or any of the excipients [see Warnings and Precautions (5.5) ] . Initiation during unresolved serious Neisseria meningitidis infection ( 4 ) Serious hypersensitivity to crovalimab or any of the excipients ( 4 )

Side Effects

  • 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the label: Serious Meningococcal Infection [see Warnings and Precautions (5.1) ] Type III Hypersensitivity Reactions Related to Drug-Target-Drug Complexes [see Warnings and Precautions (5.3) ] Other Infections [see Warnings and Precautions (5.4) ] Infusion- and Injection-Related Reactions [see Warnings and Precautions (5.

Interactions

  • 7. DRUG INTERACTIONS PIASKY binds different epitopes on C5 compared to eculizumab and ravulizumab, which can lead to the formation of DTDCs when patients switch between PIASKY and either eculizumab or ravulizumab. These DTDCs comprise one or more units of C5 bound to both PIASKY and to eculizumab or ravulizumab. These DTDCs are expected to be cleared within approximately 8 weeks (in the case of eculizumab) or longer (in the case of ravulizumab) and can result in Type III hypersensitivity reactions [see Warnings and Precautions (5.3) , Adverse Reactions (6.1) and Clinical Pharmacology (12.