| Drug Name |
PIASKY™ (crovalimab-akkz) |
| Active Ingredient |
crovalimab-akkz |
| Date of Approval |
June 20, 2024 |
| Manufacturer |
Genentech, Inc. |
| Approval Pathways and Indications |
Approval Pathway: BLA
Indication: 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. |
| Therapeutic Class |
Monoclonal Antibody |
| Formulation |
Injection: 340 mg/2 mL (170 mg/mL) in a single-dose vial for intravenous (IV) or subcutaneous (SUBQ) use |
| MoA |
PIASKY™ 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). PIASKY™ inhibits terminal complement-mediated intravascular hemolysis in patients with PNH. |
| Dosing and Administration |
The recommended dosage regimen consists of one loading dose administered by IV infusion (on Day 1), followed by four additional weekly loading doses administered by SUBQ injection (on Days 2, 8, 15, and 22). The maintenance dose starts on Day 29 and is then administered every 4 weeks by SUBQ injection. Doses are administered based on the patient’s actual body weight. For the loading dose on Day 1, if the patient weighs ≥ 40 kg to < 100 kg, then the dose is 1,000 mg IV and 340 mg SUBQ on Days 2, 8, 15, and 22. The maintenance dose is then 680 mg SUBQ starting on day 29 and repeated every 4 weeks. If the patient weights ≥ 100 kg, the loading dose on Day 1 is 1,500 mg IV and 340 mg SUBQ on Days 2, 8, 15, and 22. The maintenance dose is then 1,020 mg SUBQ starting on day 29 and repeated every 4 weeks.
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. |
| Administered by self or by HCP |
Administered by HCP |
| Place in Therapy |
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disorder of the hematopoietic stem cell associated with varying degrees of hemolytic anemia (from uncontrolled complement activation), bone marrow failure, and thrombosis. Disease-modifying treatment strategies include complement inhibition therapy and hematopoietic transplantation (HSCT), with first line treatment complement inhibitors being eculizumab or ravulizumab.
PIASKY™ showed noninferiority to eculizumab, and was initially developed with the aim of providing more convenience to patients as compared to existing therapies. Comparatively, Soliris is given by an infusion into the bloodstream every other week, while Ultomiris may be given by infusion every other month, or by weekly subcutaneous injection. With PIASKY™, patients will receive a first IV dose, followed by four SQ doses weekly. After, maintenance doses are given subcutaneously every four weeks. In patients who are switching to PIASKY™ from Ultomiris or Soliris, the first IV loading dose of PIASKY™ should be given no sooner than the time of the next scheduled dose of the previous therapy.
The product label for PIASKY™ carries a Boxed Warning for an increases the risk of serious and life-threatening infections caused by Neisseria meningitidis. 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™. 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. PIASKY™ is only available through the restricted PIASKY™ REMS program. |
| Expected Market Launch Date |
Chugai Pharmaceuticals launched PIASKY™ on May 22, 2024 but no expected launch date is available in the United States. |
| New Molecular Entity (NME) or Existing Formulation |
NME |
| Expected Cost |
Costs 1,978,062 Japanese Yen / bottle in Japan but no expected cost available in the United States |
| Product Discontinuation |
N/A |
| Clinical Trials |
The efficacy of PIASKY™ in patients with PNH was assessed in the COMMODORE 2 study (NCT04434092), a non-inferiority trial comparing PIASKY™ to eculizumab. It enrolled 204 adult patients and 6 pediatric patients (aged >12 years and ≥40 kg). Patients received a loading dose of PIASKY™ followed by weekly and then monthly maintenance doses. Vaccination against Neisseria meningitidis was required prior to or shortly after starting PIASKY™, with prophylactic antibiotics if vaccination was recent.
The primary treatment period was 24 weeks, focusing on hemolysis control, measured by lactate dehydrogenase (LDH) levels, and transfusion avoidance. In the study, 79.3% (95% CI: 72.9, 84.5) of participants treated with PIASKY™ achieved hemolysis control from week five to week 25 compared with 79.0% (95% CI: 69.7, 86.0) with eculizumab. Additionally, 65.7% (95% CI: 56.9, 73.5) achieved transfusion avoidance (TA) from baseline to week 25 with PIASKY™ and 68.1% (95% CI: 55.7, 78.5) with eculizumab. Secondary endpoints included breakthrough hemolysis and hemoglobin stabilization. Results showed similar efficacy between PIASKY™ and eculizumab, with both treatments effectively managing PNH symptoms and hemolysis, as well as maintaining hemoglobin levels without transfusions in many patients. A clinically meaningful improvement in FACIT-Fatigue score (improvement of over 5 points), which is a patient-reported scale to measure fatigue, from baseline to week 25 occurred in both arms, with an adjusted mean change of 7.8 (95% Cl: 6.5, 9.1) with PIASKY™, and 5.2 (95% Cl: 3.4, 6.9) with eculizumab. |
| Sources |
Genentech, Inc. PIASKY (eflapegrastim) prescribing information. Accessed June 26, 2024. Available at: https://www.gene.com/download/pdf/piasky_prescribing.pdf.
Drugs.com. PIASKY History. Accessed June 26, 2024. Available at:
https://www.drugs.com/history/piasky.html.
Drugs.com. PIASKY (eflapegrastim) Information. Accessed June 26, 2024.
Available at: https://www.drugs.com/piasky.html.
Onclive. FDA Approval Sought for Crovalimab for Paroxysmal Nocturnal Hemoglobinuria.
Accessed June 26, 2024. Available at:
https://www.onclive.com/view/fda-approval-sought-for-crovalimab-for-paroxysmal-nocturnal-hemoglobinuria.
FDA. Novel Drug Approvals 2024. Accessed June 26, 2024.
Available at: https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024.
Chugai Pharmaceutical Co., Ltd. Chugai Announces Approval of Crovalimab (M923)
for Paroxysmal Nocturnal Hemoglobinuria in Japan. Published May 22, 2024.
Accessed June 26, 2024.
Available at: https://www.chugai-pharm.co.
jp/english/news/detail/20240522113000_1072.html?year=2024&category=.
Chugai Pharmaceutical Co., Ltd. Chugai Announces Results from
COMMODORE 2 Study Evaluating PIASKY (eflapegrastim) in Patients
with Paroxysmal Nocturnal Hemoglobinuria. Published June 12, 2023.
Accessed June 26, 2024. Available at: https://www.chugai-pharm.co.jp/english/news/detail/20230612170001_992.html
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