PiaSky Approved for Paroxysmal Nocturnal Hemoglobinuria

On June 20, 2024, Genentech received U.S. Food and Drug Administration (FDA) approval for PiaSky (crovalimab-akkz) for the treatment of patients 13 years and older with paroxysmal nocturnal hemoglobinuria (PNH) and body weight of at least 40kg (88 pounds). PiaSky is a complement C5 inhibitor that prevents intravascular hemolysis, which is the breakdown of red blood cells (RBCs) within blood vessels. The recommended initial loading dose is administered as an intravenous (IV) infusion; patients weighing 40kg to less than 100kg should receive 1,000mg, and patients weighing 100kg or more should receive 1,500mg. Four additional weekly loading doses of 340mg should be administered by subcutaneous (SC) injection on Days 2, 8, 15, and 22 to all patients, regardless of body weight. Maintenance dosing starts on Day 29 and is then administered every four weeks by SC injection. The maintenance dose is 680mg for patients weighing 40kg to less than 100kg and 1,020mg for patients weighing at least 100kg. All doses must be administered by a healthcare professional. The labeling for PiaSky contains a boxed warning and a Risk Evaluation and Mitigation Strategy (REMS) due to the risk of severe infections that may be associated with its use. The launch is expected within the next few months. Pricing information is not yet available. Here is the full prescribing information.

At a Glance

• Brand Drug: PiaSky (crovalimab-akkz)
• Manufacturer: Genentech
• Date Approved: June 20, 2024
• Indication:  for the treatment of patients 13 years and older with paroxysmal nocturnal hemoglobinuria (PNH) and body weight of at least 40kg
• Dosage Forms Available: 340mg/2mL (170mg/mL) single-dose vials for IV infusion or SC injection
• Launch Date: Launch is expected within the next few months.
• Estimated Annual Cost: Pricing information is not currently available.
• PNH is a rare blood disorder that is caused by spontaneous mutations of a protein that attracts and holds other proteins, including some that protect against the complement parts of the immune system, onto the surfaces of red blood cells (RBCs). As a result, bone marrow produces fewer and more fragile than normal blood cells of all types. The RBCs of patients who have PNH are easily destroyed by immune proteins called complement. 
• PNH is believed to affect approximately 6,000 patients in the United States. It can cause anemia, shortness of breath, blood clots, and kidney dysfunction.
• FDA approval of PiaSky was based on a phase III study that found that it was as effective as Soliris^® (eculizumab) in treating patients with PNH.
• Common side effects in patients taking PiaSky include infusion-related reactions, respiratory tract infections, viral infections, and Type III hypersensitivity reactions.
• Because disrupting the complement system may affect immune function, PiaSky has a boxed warning and a Risk Evaluation and Mitigation Strategy (REMS) to alert prescribers and patients about the potential for life-threatening infections that may be caused by taking it. Patents should be vaccinated with a meningococcal vaccine at least two weeks prior to receiving their first dose. Prescribers and pharmacies must enroll in the REMS program and provide patients with educational materials and a Patient Safety Card to carry with them for 11 months after treatment.
• Soliris, FDA approved in 2007, and Ultomiris^® (ravulizumab-cwvz), in 2018, are C5 inhibitors that are administered by IV infusion. After five weekly doses, Soliris is infused once every two weeks. Ultomiris is given once every eight weeks, following a single loading dose, two weeks before the maintenance regimen begins. A subcutaneous on-body injector formulation of Ultomiris has also been approved by the FDA. Soliris and Ultomiris only manage intravascular hemolysis.
• Empaveli^® (pegcetacoplan) is a C3 inhibitor that was approved for PNH in 2021. It is infused subcutaneously twice weekly to manage intravascular and extravascular hemolysis. Extravascular hemolysis is the breakdown of RBCs in the liver, lymph nodes, and spleen.
• Fabhalta^® (iptacopan) was approved in Dec. 2023 for PNH. It is an oral complement factor B inhibitor that, similar to Empaveli, also manages intravascular and extravascular hemolysis.
• PiaSky is designated as an orphan drug.