Piasky
Crovalimab · Injection, Solution · Subcutaneous
Uses
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 )
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. 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). The maintenance dose starts on Day 29 and is then administered every 4 weeks by subcutaneous injection. Administer doses based on the patient's actual body weight, as shown in Table 1 . Table 1 PIASKY Dosage Regimen Based on Body Weight Body Weight ≥ 40 kg to < 100 kg ≥ 100 kg IV = intravenous, SUBQ = subcutaneous Loading Dose Day 1 Day 2, 8, 15, 22 1,000 mg (IV) 340 mg (SUBQ) 1,500 mg (IV) 340 mg (SUBQ) Maintenance Dose Day 29 and Q4W Q4W=every 4 weeks thereafter 680 mg (SUBQ) 1,020 mg (SUBQ) The dosing schedule is allowed to occasionally vary within 2 days of the scheduled administration day (except at Day 1 and Day 2). If this occurs, the subsequent dose should be administered according to the regular schedule. Modification of the maintenance dose is required if the patient's body weight changes to become consistently greater than or lower than 100 kg during the course of therapy. 2.3 Recommended Timing for Switching to PIASKY from Another C5 Inhibitor Healthcare providers should consider the benefits of the timing of switching C5 inhibitors vs. the risks of Type III hypersensitivity reactions [see Warnings and Precautions (5.3) ] . For patients switching from another C5 inhibitor (e.g., eculizumab or ravulizumab), the first intravenous loading dose of PIASKY should be administered no sooner than the time of the next scheduled complement inhibitor administration. The administration of the additional subcutaneous loading doses and maintenance doses of PIASKY should follow as per the schedule shown in Table 1 . 2.4 Delayed or Missed Dose If an entire planned dose or part of a planned dose of PIASKY is missed, administer the missed dose or remainder of the missed dose as soon as possible before the day of the next scheduled dose. Then administer the next dose on the regularly scheduled dosing day. Do not administer two doses or more than the prescribed dose on the same day to make up for a missed dose. 2.5 Preparation and Administration Each vial of PIASKY is for one-time use in only one patient. PIASKY is administered as an intravenous infusion (first dose) and as a subcutaneous injection (subsequent doses). Only healthcare providers should administer PIASKY. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. PIASKY is clear to opalescent, and an almost colorless to brownish-yellow solution. PIASKY should be discarded if the medicine looks cloudy, discolored, or has particles in it. Preparation of Intravenous Infusion Use aseptic technique to prepare PIASKY for intravenous administration. PIASKY must be diluted and administered as an intravenous infusion over 60 minutes ± 10 minutes (1,000 mg) or 90 minutes ± 10 minutes (1,500 mg). PIASKY solution must be diluted in 0.9% Sodium Chloride Injection prior to administration. A 0.2 micron in-line filter must be used with the infusion set during administration. A dedicated infusion line must be used during intravenous administration. Only dilute PIASKY in 0.9% Sodium Chloride Injection. Dilution of Intravenous Infusion Withdraw the required volume of PIASKY from the vial (see Table 2 ) using a sterile syringe and dilute into the infusion bag. Use multiple vials to meet the required volume of PIASKY to be added to the infusion bag. Discard any unused portion left in the vial. Dilution of PIASKY in infusion bags containing 0.9% Sodium Chloride Injection must be in the range of 4-15 mg/mL (final concentration after dilution) (see Table 2 ). Intravenous infusion bags of a volume of 100 mL or 250 mL can be used. Table 2 Dose Example Volume Determination Dose (mg) Volume of Piasky (mL) Size of 0.9% Sodium Chloride Injection Bag (mL) Concentration in Bag (mg/mL) 1,000 5.9 250 4 1,500 8.8 250 6 1,000 5.9 100 10 1,500 8.8 100 15 Gently mix the infusion bag by slowly inverting the bag. Do not shake. Inspect the infusion bag for particles and discard if present. Flushing of infusion line is required to ensure complete administration of the entire dose. Storage of Diluted Solution for Infusion The diluted solution for intravenous infusion should be used immediately because PIASKY does not contain any antimicrobial preservative.
Dosage forms and strengths
Injection: 340 mg/2 mL (170 mg/mL) as a clear to opalescent and almost colorless to brownish-yellow solution in a single-dose vial. Injection: 340 mg/2 mL (170 mg/mL) in a single-dose vial ( 3 )
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 )
Warnings and precautions
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. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. 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 meningococcal vaccines as soon as possible. Various durations and regimens of antibacterial drug prophylaxis have been considered, but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors, including PIASKY. The benefits and risks of treatment with PIASKY, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by N. meningitidis . Vaccination does not eliminate the risk of meningococcal infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur. Promptly treat known infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of PIASKY in patients who are undergoing treatment for serious meningococcal infection. PIASKY is available only through a restricted program under a REMS [see Warnings and Precautions (5.2) ] . 5.2 PIASKY REMS PIASKY is available only through a restricted program under a REMS called PIASKY REMS, because of the risk of serious meningococcal infections [see Warnings and Precautions (5.1) ] . Notable requirements of the PIASKY REMS include the following: Prescribers must enroll in the REMS. Prescribers must counsel patients about the risk of serious meningococcal infection. Prescribers must provide the patients with the REMS educational materials. Prescribers must assess patient vaccination status for meningococcal vaccines (against serogroups A, C, W, Y, and B) and vaccinate if needed according to current ACIP recommendations two weeks prior to the first dose of PIASKY. Prescribers must provide a prescription for antibacterial drug prophylaxis if treatment must be started urgently, and the patient is not up to date with both meningococcal vaccines according to current ACIP recommendations at least two weeks prior to the first dose of PIASKY. Healthcare settings and pharmacies that dispense PIASKY must be certified in the REMS and must verify prescribers are certified. Patients must receive counseling from the prescriber about the need to receive meningococcal vaccines per ACIP recommendations, the need to take antibiotics as directed by the prescriber, and the signs and symptoms of meningococcal infection. Patients must be instructed to carry the Patient Safety Card with them at all times during and for 11 months following treatment with PIASKY. Further information is available at www.PIASKYREMS.com or 1-866-4My-Skyy (469-7599). 5.3 Type III Hypersensitivity Reactions Related to Drug-Target-Drug Complexes Patients who are switching from another C5 inhibitor (e.g., eculizumab or ravulizumab) to PIASKY or from PIASKY to another C5 inhibitor are at risk of serious Type III hypersensitivity reactions related to the formation of drug-target-drug-complexes (DTDCs), because PIASKY and these other C5 inhibitors bind different epitopes of C5 [see Drug Interactions (7) ] . In clinical trials, Type III hypersensitivity reactions were reported in 39 of 201 patients (19%) who switched from eculizumab or ravulizumab to PIASKY. Four of these patients (10%) had not fully recovered from symptoms of Type III hypersensitivity reactions at the time of their last follow up visit. In addition, Type III hypersensitivity reactions were reported in 2 of 8 patients (25%) who switched from PIASKY to eculizumab or ravulizumab, including one patient who developed Grade 3 axonal neuropathy [see Adverse Reactions (6) ] . Symptoms of Type III hypersensitivity reactions that occurred in more than 2 patients were arthralgia, rash, pyrexia, myalgia, headache, fatigue, petechiae and abdominal pain.
Side effects
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) ] . Serious adverse reactions occurred in 6% of patients receiving PIASKY in the COMMODORE 2 study, including epistaxis and pneumonia, which occurred in 2 patients each, and infusion related reaction, pyelonephritis, COVID-19, and hypovolemic shock which were reported in 1 patient each. Table 4 lists adverse reactions that occurred at a rate of 5% or more among patients randomized to PIASKY treatment for 24 weeks in the COMMODORE 2 study. The most common adverse reactions (≥10%) in patients treated with PIASKY were infusion related reaction, respiratory tract infection, and viral infection. Table 4 Adverse Reactions Reported In 5% or More of Complement-Inhibitor Naïve Patients with PNH Randomized to PIASKY in COMMODORE 2 Adverse reactions PIASKY (N = 135) % ECULIZUMAB (N = 69) % Infusion-related reaction 16 13 Respiratory tract infection Grouped terms. Diarrhea includes diarrhea and diarrhea infectious. Headache includes headache and migraine. Injection-related reaction includes injection related reaction and injection site reaction. Respiratory tract infection includes nasopharyngitis, pharyngitis, rhinitis, rhinitis allergic, upper respiratory tract infection and pneumonia. Viral infection includes viral infection, COVID-19, influenza, herpes virus infection and oral herpes. 13 20 Viral infection 11 7 Hyperuricemia 8 9 Headache 8 6 Diarrhea 7 1 Injection-related reaction Injection-related reactions are only expected to occur in the PIASKY arm as eculizumab is not given by subcutaneous injection 6 0 Patients Previously Treated with a Complement C5 Inhibitor The data described below reflect exposure of 86 patients with PNH who received PIASKY (n=44) or eculizumab (n=42) at the recommended dosing regimen for 24 weeks in COMMODORE 1, an open-label, active-controlled, multicenter study conducted in patients switching from eculizumab. The median age was 47 years (range: 21 to 85); 52% were female, and race included White (73%), Asian (19%), unknown (5%), and Black/African-American (3%). The population ethnicities were 17% Hispanic or Latino and 76% not Hispanic or Latino. Serious adverse reactions in COMMODORE 1 were reported in 3 patients (7%) with PNH receiving PIASKY. Serious adverse reactions included pneumonia, nasopharyngitis, and urinary tract infection, which occurred in 1 patient each. Table 5 lists adverse reactions that occurred at a rate of 5% or more among patients randomized to PIASKY treatment for 24 weeks in the COMMODORE 1 study. The most common adverse reactions (≥10%) in patients treated with PIASKY were viral infections, respiratory tract infection, Type III hypersensitivity reaction, infusion-related reaction, peripheral edema, and headache. Table 5 Adverse Reactions Reported In 5% or More of Complement-Inhibitor Treated Patients with PNH Randomized to PIASKY in COMMODORE 1 Adverse reactions PIASKY (N = 44) % ECULIZUMAB (N = 42) % Viral infection Grouped terms Fatigue includes fatigue, malaise and asthenia. Injection-related reaction includes injection related reaction and injection site reaction. Rash includes rash and skin exfoliation. Peripheral edema includes edema peripheral and peripheral swelling. Respiratory tract infection includes respiratory tract infection, nasopharyngitis, pneumonia and upper respiratory tract infection. Viral infection includes viral infection, influenza, COVID-19, and respiratory syncytial virus infection 23 21 Respiratory tract infection 18 5 Type III hypersensitivity reaction Type III immune complex mediated reaction is only expected to occur in the PIASKY arm as patients in the eculizumab arm did not change C5 inhibitor treatment 16 0 Infusion-related reaction Infusion-related reactions are not expected to occur in the eculizumab arm as these patients tolerated eculizumab prior to study initiation 14 0 Peripheral edema 11 2 Headache 11 2 Injection-related reaction Injection-related reactions are only expected to occur in the PIASKY arm as eculizumab is not given by subcutaneous injection 9 0 Fatigue 9 12 Rash 9 0 Diarrhea 7 2 Nausea 7 5 Arthralgia 7 0 Type III Hypersensitivity Reactions Related to Drug-Target-Drug Complexes [see Warnings and Precautions (5.3) , and Drug Interactions (7) ] . Across the COMMODORE 1 and 2 studies, 39 out of 201 (19.4%) patients who switched from eculizumab or ravulizumab to PIASKY experienced a Type III hypersensitivity reaction (reported as Type III immune complex mediated reaction).
Drug 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 (12.3) ] .
Use in specific populations
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. Clinical Considerations Disease-associated maternal and/or fetal/neonatal risk PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombosis, infections, bleeding, miscarriages, and increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery. Data Animal data In an enhanced pre- and post-natal development study, pregnant cynomolgus monkeys were given an intravenous loading dose of crovalimab-akkz 100 mg/kg on gestation day (GD) 20 followed by weekly subcutaneous injections of up to 100 mg/kg up to parturition. The dams and infants were then observed untreated for 6 months. There were no adverse effects of crovalimab-akkz on pregnancy or on the viability, growth, and development of the infants up to 100 mg/kg at exposures 14-times the human exposure at the MRHD, based on area under the concentration-time curve (AUC). 8.2 Lactation Risk Summary There are no data on the presence of crovalimab-akkz in either human or animal milk, the effects on the breastfed child or on milk production. Endogenous IgG and monoclonal antibodies are transferred in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to crovalimab-akkz is unknown. Because of the potential for serious adverse reactions in a breastfed child, advise patients that breastfeeding is not recommended during treatment with PIASKY and for 9 months after the final dose. 8.4 Pediatric Use The safety and effectiveness of PIASKY for the treatment of PNH have been established in pediatric patients 13 years and older with a body weight ≥ 40 kg. Use of PIASKY for this indication in pediatric patients is supported by evidence from adequate and well-controlled studies in adults along with additional pharmacokinetic, pharmacodynamic, efficacy and safety data in pediatric patients aged 13 to 17 years [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14.1) ] . The safety and effectiveness of PIASKY have not been established in pediatric patients less than 13 years of age and in those with body weight < 40 kg. 8.5 Geriatric Use Clinical studies of PIASKY did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for elderly patients should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other therapy. Of the 393 PIASKY-treated patients in COMMODORE 1, 2 and 3, 43 (10.9%) were 65 years of age and older. In patients who were complement inhibitor naïve, serious adverse reactions were reported in 1 patient (8%) who was 65 years or older compared to 6 (4%) patients who were 18 to 64 years of age. In patients who previously received a different C5 inhibitor and switched to PIASKY, serious adverse reactions were reported in 3 (7%) patients who were 65 years or older compared to 12 (4%) patients who were 18 to 64 years of age.
Pregnancy
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. Clinical Considerations Disease-associated maternal and/or fetal/neonatal risk PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombosis, infections, bleeding, miscarriages, and increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery. Data Animal data In an enhanced pre- and post-natal development study, pregnant cynomolgus monkeys were given an intravenous loading dose of crovalimab-akkz 100 mg/kg on gestation day (GD) 20 followed by weekly subcutaneous injections of up to 100 mg/kg up to parturition. The dams and infants were then observed untreated for 6 months. There were no adverse effects of crovalimab-akkz on pregnancy or on the viability, growth, and development of the infants up to 100 mg/kg at exposures 14-times the human exposure at the MRHD, based on area under the concentration-time curve (AUC).
Pediatric use
8.4 Pediatric Use The safety and effectiveness of PIASKY for the treatment of PNH have been established in pediatric patients 13 years and older with a body weight ≥ 40 kg. Use of PIASKY for this indication in pediatric patients is supported by evidence from adequate and well-controlled studies in adults along with additional pharmacokinetic, pharmacodynamic, efficacy and safety data in pediatric patients aged 13 to 17 years [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14.1) ] . The safety and effectiveness of PIASKY have not been established in pediatric patients less than 13 years of age and in those with body weight < 40 kg.
Geriatric use
8.5 Geriatric Use Clinical studies of PIASKY did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for elderly patients should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other therapy. Of the 393 PIASKY-treated patients in COMMODORE 1, 2 and 3, 43 (10.9%) were 65 years of age and older. In patients who were complement inhibitor naïve, serious adverse reactions were reported in 1 patient (8%) who was 65 years or older compared to 6 (4%) patients who were 18 to 64 years of age. In patients who previously received a different C5 inhibitor and switched to PIASKY, serious adverse reactions were reported in 3 (7%) patients who were 65 years or older compared to 12 (4%) patients who were 18 to 64 years of age.
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. PIASKY (crovalimab-akkz) injection is a preservative-free, sterile, clear to opalescent, almost colorless to brownish-yellow, solution supplied in a single-dose vial for intravenous use or subcutaneous use. Intravenous use requires dilution prior to administration. Each single-dose vial contains a 2 mL solution of crovalimab-akkz (340 mg), arginine hydrochloride (42.2 mg), histidine (9.4 mg), poloxamer 188 (1 mg), and Water for Injection USP. The pH is 5.8. Aspartic acid may be added to adjust the pH.
Mechanism of action
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.
How supplied
16.1 How Supplied PIASKY (crovalimab-akkz) injection is a sterile, preservative-free, clear to opalescent, and almost colorless to brownish-yellow solution. Each PIASKY carton contains one 340 mg/2 mL (170 mg/mL) single-dose vial (NDC 50242-115-01). 16.2 Storage and Handling Store refrigerated at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light. Do not freeze. Do not shake. Once removed from the refrigerator, the unopened vial can be kept at room temperature up to 30°C (86°F) in its outer carton for no longer than 7 days. Prior to administration, unopened vials of PIASKY may be stored out of the refrigerator at room temperature if needed and then returned to refrigeration. The total combined time out of refrigeration should not exceed 7 days and the temperature should not exceed 30°C (86°F). Discard if stored out of the refrigerator at room temperature for longer than 7 days.
Storage
16.2 Storage and Handling Store refrigerated at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light. Do not freeze. Do not shake. Once removed from the refrigerator, the unopened vial can be kept at room temperature up to 30°C (86°F) in its outer carton for no longer than 7 days. Prior to administration, unopened vials of PIASKY may be stored out of the refrigerator at room temperature if needed and then returned to refrigeration. The total combined time out of refrigeration should not exceed 7 days and the temperature should not exceed 30°C (86°F). Discard if stored out of the refrigerator at room temperature for longer than 7 days.
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Serious Meningococcal Infection Advise patients of the risk of serious meningococcal infection. Inform patients of the need to complete or update their meningococcal vaccinations at least 2 weeks prior to receiving the first dose of PIASKY or receive antibacterial drug prophylaxis if PIASKY treatment must be initiated immediately and they have not previously been vaccinated. Inform patients of the requirement to be revaccinated according to current ACIP recommendations for meningococcal infection while on PIASKY therapy. Inform patients that vaccination may not prevent serious meningococcal infection and to seek immediate medical attention if the following signs or symptoms occur [see Warnings and Precautions (5.1) ] . fever fever and a rash headache with nausea or vomiting fever with a high heart rate headache and a fever headache with a stiff neck or stiff back confusion muscle aches, with flu-like symptoms eye sensitive to light Inform patients that they will be given a Patient Safety Card for PIASKY that they should carry with them at all times during and for 11 months following treatment with PIASKY. This card describes symptoms which, if experienced, should prompt the patient to immediately seek medical evaluation. PIASKY REMS PIASKY is available only through a restricted program called PIASKY REMS [see Warnings and Precautions (5.2) ] . Inform the patient of the following requirements: Patients must receive counseling about the risk of serious meningococcal infections. Patients must receive written educational materials about this risk. Patients must be instructed to carry the Patient Safety Card with them at all times during and for 11 months following treatment with PIASKY. Patients must be instructed to complete or update meningococcal vaccines for serogroups A, C, W, Y and B per ACIP recommendations as directed by the prescriber prior to treatment with PIASKY. Patients must receive antibiotics as directed by the prescriber if they are not up to date with meningococcal vaccines and have to start PIASKY right away. Type III Hypersensitivity Reactions Inform patients of the risk of experiencing a Type III hypersensitivity reaction in the first 30 days after switching from another C5 inhibitor to PIASKY (or if they are planning to switch from PIASKY to another C5 inhibitor) [see Warnings and Precautions (5.3) ] . Inform patients about the signs and symptoms of a Type III hypersensitivity reaction, and advise patients to seek immediate medical attention if the following signs or symptoms occur: rash itching joint pain numbness and tingling or a feeling of pins and needles, especially of the hands and feet Other Infections Counsel patients of the increased risk of infections, particularly those due to encapsulated bacteria, especially Neisseria species [see Warnings and Precautions (5.4) ] . Advise patients of the need for vaccination against Streptococcus pneumoniae infections according to current ACIP recommendations. Inform parents or caregivers of children receiving PIASKY that their child should be vaccinated against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) according to current medical guidelines. Advise patients to report any new signs and symptoms of infection. Infusion- and Injection-Related Reactions Advise patients that administration of PIASKY may result in infusion-related reactions or systemic injection-related reactions depending on the route of administration [see Warnings and Precautions (5.5) ] . Advise patients to seek immediate medical attention if symptoms of serious allergic reactions occur. Discontinuation of PIASKY Inform patients that they may develop hemolysis due to PNH when PIASKY is discontinued and that they will be closely monitored by their healthcare professional for at least 20 weeks following PIASKY discontinuation [see Warnings and Precautions (5.6) ] . Inform patients who discontinue PIASKY to keep the Patient Safety Card with them for 11 months after the last PIASKY dose, because the increased risk of meningococcal infection persists for several months following discontinuation of PIASKY [see Warnings and Precautions (5.1 and 5.2) ] . Lactation Advise patients it is not recommended to breastfeed during treatment with PIASKY and for 9 months after the final dose [see Use in Specific Populations (8.2) ] .
Label text from the FDA structured product label by Genentech, Inc. (revised Nov 11, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Crovalimab in 1 product
Piasky NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50242-115 | Crovalimab 340 mg/2mL Injection, Solution | Genentech, Inc. | BLA |
Frequently asked questions
What is Piasky used for?
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 )
What are the side effects of Piasky?
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 the full label for the complete list.
Who makes Piasky?
Piasky is listed by 1 labeler in the FDA NDC directory, including Genentech, Inc..