On Nov. 9, 2023, the U.S. Food and Drug Administration (FDA) approved Adzynma^® (ADAMTS13, recombinant-krhn – Takeda) for prophylaxis or on-demand enzyme replacement therapy (ERT) in adult and pediatric patients who have congenital thrombotic thrombocytopenic purpura (cTTP). Adzynma is recombinant “A disintegrin and metalloproteinase with thrombospondin motifs 13” (ADAMTS13) protein that helps reduce platelet binding of von Willebrand factor (VWF), thereby preventing small blood clots. It is administered intravenously (IV) at a prophylactic dose of 40 IU/kg once every other week or it can be adjusted to once weekly based on clinical response and prior dosing. For acute events, the dose is administered IV at 40 IU/kg on day 1, 20 IU/kg on day 2, and then 15 IU/kg daily until two days after resolution. A launch date, pricing, and distribution have not been announced. For full prescribing information see here.

At a Glance

• Brand (Generic) Name: Adzynma (ADAMTS13, recombinant-krhn)
• Manufacturer: Takeda
• Date Approved: Nov. 9, 2023
• Indication: for prophylactic or on-demand ERT in adult and pediatric patients with cTTP
• Dosage Forms Available: single-dose vials containing 500 IU or 1500IU of lyophilized powder for reconstitution
• Launch Date: The launch date isn’t known at this time.
• Estimated Annual Cost: Pricing information is not yet available.
• Caused by a mutation in the ADAMTS 13 gene, cTTP is an inherited clotting disorder that causes clots in small blood vessels.
• In the U.S., cTTP is estimated to affect fewer than 1,000 people. If left untreated, acute attacks have a mortality rate of over 90%.
• Patients who are affected by cTTP may have bleeding episodes, clots, strokes, organ damage, or possibly death. The disease usually develops during infancy, but it can be diagnosed for adults or it can be brought on by pregnancy.
• No other FDA-approved products are indicated for cTTP.
• Patients typically are treated with plasma-based products or fresh frozen plasma to replace the ADAMTS13 enzyme.
• In phase III clinical trials, 46 patients were randomized to be treated with Adzynma or plasma therapy for six months and then patients in each group crossed over to the other treatment for six months. During treatment with Adzynma, no patients experienced an acute TTP event, defined as a 50% or more drop in platelet count from baseline or a platelet count of less than 100,000/µL. One acute event occurred for a participant who was receiving plasma-based therapy. Additionally, no subacute events occurred during Adzynma treatment, but five were seen during plasma treatment. They included thrombocytopenia, microangiopathic hemolytic anemia, organ-specific events, fever, abdominal pain, neurological symptoms, or fatigue.
• The most common adverse events (AEs) were headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness, and vomiting.
• Adzynma was approved with Priority Review, Fast Track, and Orphan Drug designations. Takeda also was granted a Rare Pediatric Disease Voucher that it can use for priority review in the future for a different product.