Piasky340 mg/2mL · Injection, Solution

• 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 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.

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.

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.

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. If immediate use is not possible, see Table 3 for detailed storage conditions of the prepared solution for infusion, which depends on the type of infusion bags used.
• Table 3 Storage Conditions for the Prepared Solution for Infusion
• Infusion bags Storage conditions
• polyolefins (PO), polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC)
• PO/PE/PP Refrigerate at 2°C to 8°C (36°F to 46°F) for up to 64 hours protected from light, and store at room temperature up to 30°C (86°F) for up to 6 hours including infusion time under ambient light conditions. Protect from direct sunlight.
• PVC Refrigerate at 2°C to 8°C (36°F to 46°F) for up to 12 hours protected from light, and store at room temperature up to 30°C (86°F) for up to 6 hours including infusion time under ambient light conditions. Protect from direct sunlight.
• No incompatibilities have been observed between PIASKY and intravenous infusion bags with product-contacting materials made of polyvinyl chloride, or polyolefins such as polyethylene and polypropylene. In addition, no incompatibilities have been observed with infusion sets or infusion aids with product-contacting materials made of polyvinyl chloride, polyethylene, polyurethane, polybutadiene, acrylonitrile butadiene styrene, polycarbonate, or polytetrafluorethylene.
• The infusion of PIASKY may be slowed or interrupted if the patient develops an infusion-related reaction. The infusion should be discontinued immediately if the patient experiences a serious hypersensitivity reaction [see Warnings and Precautions (5.5)].
• Preparation of the Subcutaneous Injection
• For subcutaneous injection, PIASKY must be used undiluted.
• Remove the vial cap and clean the vial rubber stopper.
• Attach the transfer needle on the syringe.
• Withdraw all the medicine from the vial.
• Remove air bubbles if any.
• Remove the transfer needle from the vial.
• Recap the transfer needle using a one-handed scoop technique.
• Detach the transfer needle.
• Attach the injection needle on the syringe.
• Clean the injection site with an alcohol pad and let air dry.
• Inject the medicine subcutaneously.
• If the dose requires multiple injections, perform a new injection using a new PIASKY vial.
• A syringe, a transfer needle and an injection needle are needed to withdraw PIASKY solution from the vial and inject it subcutaneously.
• A 2 mL or 3 mL syringe fulfilling the following criteria are recommended: Transparent polypropylene or polycarbonate syringe with Luer-Lock tip (if not available, a syringe with Luer Slip tip can be used), sterile, single-use, latex-free and non-pyrogenic, and commercially available in the US.
• A transfer needle without a filter fulfilling the following criteria may be used: Stainless steel, sterile, preferably gauge 18 G with single bevel at approximately 45 degrees to reduce risk of needle stick injury (or gauge 21 G standard needle as an alternative), single-use, latex-free and non-pyrogenic, and commercially available in the US.
• An injection needle fulfilling the following criteria may be used: Hypodermic needle, stainless steel, sterile, gauge 25 G, 26 G or 27 G, length 3/8'' to 1/2'', single-use, latex-free and non-pyrogenic, preferably including safety needle shield, and commercially available in the US.
• Each injection is a volume of 2 mL PIASKY, corresponding to 340 mg. A 2 mL-size or 3 mL-size syringe should be used for each injection. A dose of 680 mg is achieved by performing two consecutive subcutaneous injections of 340 mg. A dose of 1020 mg is achieved by performing three consecutive subcutaneous injections of 340 mg.
• Inject PIASKY subcutaneously in the abdomen region and rotate abdominal injection sites with every injection. Consecutive injections must be at least 2 inches apart. No data are available on injection at other sites of the body. Injections should never be given into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.
• Storage of Solution for Injection
• Once transferred from the vial to the syringe, PIASKY should be injected immediately because PIASKY does not contain any antimicrobial-preservative. If immediate use is not possible, the capped syringe can be refrigerated at 2°C to 8°C (36°F to 46°F) for up to 64 hours protected from light and stored at room temperature up to 30°C (86°F) for up to 5 hours under ambient light conditions.
• Protect from direct sunlight.

• 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 13 20
• Viral infection 11 7
• Hyperuricemia 8 9
• Headache 8 6
• Diarrhea 7 1
• Injection-related reaction 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 23 21
• Respiratory tract infection 18 5
• Type III hypersensitivity reaction 16 0
• Infusion-related reaction 14 0
• Peripheral edema 11 2
• Headache 11 2
• Injection-related reaction 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). A total of 6 patients had switched two times and of the 6 patients, 2 patients experienced a second episode of Type III hypersensitivity reaction after discontinuing PIASKY and switching to ravulizumab. One of these patients developed Grade 3 axonal neuropathy and a Type III hypersensitivity reaction could not be excluded and the other developed Grade 2 arthralgia and myalgia. These two events remained unresolved at the last follow up visit of the clinical studies (the duration of the events until last follow-up was 313 days for the event of Grade 3 axonal neuropathy and 142 days for the event of Grade 2 arthralgia and myalgia, respectively). Two additional patients who experienced Grade 3 rash and Grade 3 arthralgia, respectively, had unresolved Type III hypersensitivity reaction at the last follow-up visit.
• The median time to onset of Type III hypersensitivity reaction in patients who switched treatment from eculizumab or ravulizumab to PIASKY was 1.6 weeks (range: 0.7 – 4.4 weeks) and the median duration of Type III hypersensitivity reactions was 1.9 weeks (range 0.4 – 34.1 weeks). The majority of events were Grade 1-2. Grade 3 Type III hypersensitivity reaction occurred in 8% of patients who switched from eculizumab or ravulizumab to PIASKY. Out of 42 Type III hypersensitivity reactions, 37 (88%) resolved, including 1 (2.4%) that resolved with PIASKY discontinuation, 2 (4.8%) that resolved with PIASKY interruption and 34 (81%) that resolved without discontinuation, interruption, or dose change in PIASKY therapy.
• Axonal Neuropathy
• In COMMODORE 1 and 2, Grade 3 distal axonal demyelinating polyneuropathy and Grade 3 axonal neuropathy were reported, each in 1 patient who switched from another C5 inhibitor to PIASKY or from PIASKY to another C5 inhibitor. The Grade 3 distal axonal demyelinating polyneuropathy occurred 11 weeks after a patient switched from eculizumab to PIASKY (with first dose of PIASKY received 12 days after the last dose of eculizumab treatment) and was preceded by a bacterial respiratory tract infection. The Grade 3 axonal neuropathy occurred in a patient who had switched to ravulizumab treatment after 6 weeks of treatment with PIASKY, and previously received ravulizumab treatment prior to switching to treatment with PIASKY [see Warnings and Precautions (5.3)]. Events associated with the axonal neuropathy included COVID-19, sepsis and administration of a fluoroquinolone. In both cases of axonal neuropathy, a Type III hypersensitivity reaction as a cause of, or contributor to, the axonal neuropathy could not be excluded. Both cases of axonal neuropathy remained unresolved at the last follow up visit of the clinical studies.
• Pediatric Population with PNH Treated with PIASKY
• Twelve pediatric patients with PNH (9 treatment-naïve patients and 3 patients who switched from another C5 inhibitor) were treated with PIASKY in COMMODORE 1 (n=2), COMMODORE 2 (n=7), and in a single-arm trial [(COMMODORE 3 (n=3)]. The safety profile of PIASKY appeared comparable between adult and pediatric patients, but conclusions are limited by the small number of pediatric patients.

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) ] .