Takeda’s ADZYNMA (ADAMTS13, recombinant-krhn) Approved by U.S. FDA as the First and Only Recombinant ADAMTS13 Enzyme Replacement Therapy for the Treatment of Congenital Thrombotic Thrombocytopenic Purpura (cTTP)

Takeda announced that the U.S. Food and Drug Administration (FDA) has approved ADZYNMA (ADAMTS13, recombinant-krhn) for the prophylactic and on-demand treatment of adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP). ADZYNMA is the first and only FDA-approved recombinant ADAMTS13 (rADAMTS13) protein designed to address an unmet medical need in people with cTTP by replacing the deficient ADAMTS13 enzyme.

“People living with cTTP face serious, life-threatening health challenges, and until today, were without any approved treatment specifically indicated for their disease,” said Julie Kim, president, U.S. Business Unit and U.S. country head at Takeda. “As we strive to help patients with limited or no treatment options, developing innovative treatments in rare diseases is an inspiring challenge and one we have taken on for 70-plus years as a leader in hematology. Today, we are proud to further support the rare disease community by delivering ADZYNMA as the first FDA-approved therapeutic option for people with cTTP.”

cTTP is an ultra-rare, chronic blood clotting disorder caused by a deficiency in the ADAMTS13 enzyme. It is associated with acute events and debilitating chronic symptoms or thrombotic thrombocytopenic purpura (TTP) manifestations, which can include thrombocytopenia, microangiopathic hemolytic anemia, headache and abdominal pain. When left untreated, acute TTP events have a mortality rate of >90%.

“In recent decades, significant progress has been made to better understand the link between ADAMTS13 deficiency and cTTP, ultimately leading to this moment where we finally have an FDA-approved treatment option for patients living with this rare disease,” said Spero R. Cataland, M.D., professor of internal medicine at the Wexner Medical Center at The Ohio State University, co-director at the U.S. Thrombotic Microangiopathy Alliance (USTMA) and ADZYNMA clinical trial investigator. “ADZYNMA provides patients with a treatment option that replaces their deficient ADAMTS13 enzyme and offers a favorable efficacy and safety profile and reduced administration time and volume compared to current plasma-based therapies. Today marks a significant achievement, providing new possibilities for the cTTP patient community.”

The FDA approval of ADZYNMA was supported by the totality of the evidence provided by the analysis of efficacy, pharmacokinetic, safety and tolerability data from the first randomized, controlled, open-label, crossover Phase 3 trial in cTTP as well as by data from the continuation trial. In the Phase 3 trial, patients received 40 IU/kg ADZYNMA IV or plasma-based therapy every other week or weekly based on regimen at enrollment for months 1-6 (period 1), crossing over to the alternate treatment for months 7-12 (period 2), and all patients received ADZYNMA for months 13-18 (period 3).

No patient experienced an acute TTP event while receiving ADZYNMA prophylactic treatment (n=37), while there was one acute TTP event in a patient receiving plasma-based therapies (n=38). No subacute TTP events were reported in patients receiving ADZYNMA during the Phase 3 study-controlled comparison periods 1 and 2, compared to five subacute TTP events in four patients receiving plasma-based therapies. In the continuation period (period 3), two patients receiving ADZYNMA prophylaxis had two subacute events.

The mean annualized event rate (SD) of thrombocytopenia manifestations was 2.0 (4.706) for patients receiving ADZYNMA (9/37 patients experienced a manifestation) compared to 4.44 (6.312) in patients receiving plasma-based therapies (19/38 patients experienced a manifestation). While the clinical significance of the comparison is unknown, thrombocytopenia is a manifestation of TTP, and as such is an important biomarker of disease activity.

ADZYNMA is a recombinant form of the ADAMTS13 protein. In a pharmacokinetic assessment, patients receiving 40 IU/kg ADZYNMA IV (n=23) achieved a four-to five-fold increase in ADAMTS13 activity following a single infusion compared to plasma-based therapies.

ADZYNMA demonstrated a favorable safety profile compared to plasma-based therapies. The most common adverse reactions (incidence >5%) were headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness and vomiting. No patients receiving ADZYNMA developed neutralizing antibodies.

This approval does not result in any changes to Takeda’s consolidated forecast for the fiscal year ending March 31, 2024 (FY2023).