Crovalimab

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.

• 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 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) ] .contraindicated

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. See Full Prescribing Information for considerations when switching from another C5 inhibitor. Administer doses based on the patient's actual body weight ( 2.2 ) 2.1 Recommended Vaccination and Prophylaxis for Meningococcal Infection Vaccinate patients for meningococcal infection (serogroups A, C, W, Y and B) according to current ACIP recommendations at least 2 weeks prior to initiation of PIASKY [see Warnings and Precautions (5.1) ] . If urgent PIASKY therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible. Healthcare providers who prescribe PIASKY must enroll in the PIASKY REMS [see Warnings and Precautions (5.2) ]. 2.2 Recommended Dosage Regimen The recommended dosage regimen consists of one loading dose administered by intravenous (IV) infusion (on Day 1), followed by four additional weekly loading doses administered by subcutaneous (SUBQ) injection (on Days 2, 8, 15, and 22).

Type III hypersensitivity reactions: Monitor patients switching from another C5 inhibitor to PIASKY or from PIASKY to another C5 inhibitor as they are at risk of Type III hypersensitivity reactions related to the formation of drug-target-drug complexes ( 5.3 ) Other Infections: PIASKY can increase susceptibility to serious infections especially those caused by encapsulated bacteria. ( 5.4 ) Infusion- and Injection-Related Reactions: Monitor for these reactions and initiate medical management as needed ( 5.5 ) 5.1 Serious Meningococcal Infection PIASKY, a complement inhibitor, increases a patient's susceptibility to serious, life-threatening, or fatal infections caused by meningococcal bacteria (meningococcemia and/or meningitis) in any serogroup, including non-groupable strains. Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of PIASKY is contraindicated in patients with a serious unresolved Neisseria meningitidis infection. Complete or update meningococcal vaccination (for serogroups A, C, W, Y, and B) at least 2 weeks prior to administration of the first dose of PIASKY, according to the current Advisory Committee on Immunization Practices (ACIP) recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of PIASKY therapy.

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 (5.5) ] The most common adverse drug reactions (incidence ≥10%) were infusion-related reaction, respiratory tract infection, viral infection, and Type III hypersensitivity reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial 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. Patients Who are Complement Inhibitor-Naïve The data described below reflect exposure of 204 patients with PNH who were complement inhibitor-naïve and who were randomized in COMMODORE 2 to receive PIASKY (n = 135) or eculizumab (n = 69) at the recommended dosing regimen for 24 weeks [see Clinical Studies (14) ] .

8. USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding not recommended ( 8.2 ) 8.1 Pregnancy Risk Summary Available data on PIASKY use in pregnant women are insufficient to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Human IgG antibody is known to cross the placenta and its transport increases as pregnancy progresses and peaks during the third trimester; therefore, PIASKY may be transmitted from the mother to the developing fetus. There are risks to the mother and fetus associated with untreated PNH in pregnancy (see Clinical Considerations ). In an enhanced pre- and postnatal development study, no adverse developmental outcomes were observed when monkeys were exposed to crovalimab-akkz during the period of organogenesis through parturition at doses that produced maternal exposures 14-times the exposures at the maximum recommended human dose (MRHD), (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.

Metabolism

Crovalimab-akkz exhibits dose proportional pharmacokinetics over the dose range from 75 to 1500 mg when given as a single intravenous infusion and from 100 to 1020 mg when given as a subcutaneous injection. Following the first intravenous loading dose, crovalimab-akkz concentrations exceeded the target threshold for complete terminal complement inhibition (100 µg/mL).

• Jun 20, 2024BLABLA761388Genentech Inc

1. 1Type Iii Immune Complex Mediated Reaction1923%
2. 2Pyrexia1822%
3. 3Anaemia1519%
4. 4Haemolysis1012%
5. 5Off Label Use1012%
6. 6Infection911%
7. 7Pneumonia78.6%
8. 8Sepsis78.6%
9. 9Urinary Tract Infection67.4%
10. 10Breakthrough Haemolysis56.2%
11. 11Covid-1956.2%
12. 12Drug Ineffective56.2%
13. 13Haemoglobin Decreased56.2%
14. 14Headache56.2%
15. 15Hepatic Function Abnormal56.2%

The 10 most recently updated of 10 ClinicalTrials.gov registrations naming Crovalimab as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study to Assess Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Healthy Volunteers and Participants With Paroxysmal Nocturnal Hemoglobinuria
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 59 enrolled · Hoffmann-La Roche
  NCT03157635updated 2026-05-14
• A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition
  Active not recruiting · Phase 3 · Interventional · 51 enrolled · Hoffmann-La Roche
  NCT04654468updated 2026-05-12
• A Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab as Adjunct Treatment in Prevention of Vaso-Occlusive Episodes (VOE) in Sickle Cell Disease (SCD)
  Completed · Phase 2 · Interventional · 95 enrolled · Hoffmann-La Roche
  NCT05075824updated 2026-04-30
• A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
  Active not recruiting · Phase 3 · Interventional · 190 enrolled · Hoffmann-La Roche
  NCT04432584updated 2026-04-28
• A Study Evaluating the Efficacy and Safety of Crovalimab Versus Eculizumab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibitors
  Active not recruiting · Phase 3 · Interventional · 210 enrolled · Hoffmann-La Roche
  NCT04434092updated 2026-04-28
• A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
  Active not recruiting · Phase 3 · Interventional · 83 enrolled · Hoffmann-La Roche
  NCT04861259updated 2026-04-23
• A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
  Active not recruiting · Phase 3 · Interventional · 41 enrolled · Hoffmann-La Roche
  NCT04958265updated 2026-03-27
• A Study to Evaluate Crovalimab in People With Antiphospholipid Syndrome (APS)
  Withdrawn · Phase 2 · Interventional · 0 enrolled · Hoffmann-La Roche
  NCT07172022updated 2026-03-02
• A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes (VOE) in Participants With Sickle Cell Disease (SCD).
  Completed · Phase 1 · Interventional · 30 enrolled · Hoffmann-La Roche
  NCT04912869updated 2025-08-26
• A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Participants With Guillain-Barré Syndrome (GBS)
  Withdrawn · Phase 3 · Interventional · 0 enrolled · Hoffmann-La Roche
  NCT05494619updated 2022-12-15

Frequently asked questions

How does Crovalimab work?

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.

What is Crovalimab used for?

According to FDA labeling, Crovalimab carries indications including: 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Crovalimab?

Crovalimab is classified as Complement inhibitors, Complement C5 Inhibitor, Complement C5 Inhibitors, Complement Inhibitors, Decreased Complement Activity.

What are the brand names for Crovalimab?

Crovalimab is marketed under brand names including Piasky.

What are the contraindications for Crovalimab?

Crovalimab labeling lists contraindications including: 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) ] .. Always consult the full prescribing information and a clinician.