FDA Approves Adzynma for Congenital Thrombotic Thrombocytopenic Purpura

Spero R. Cataland, MD

Credit: The Ohio State University

The US Food and Drug Administration (FDA) has approved Adzynma as prophylactic or on-demand enzyme replacement therapy in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).

Announced on November 9, 2023, the approval was granted to Takeda Pharmaceuticals based on data from a global study demonstrating the safety and efficacy of prophylactic and on-demand enzyme replacement therapy with Adzynma compared to plasma-based therapies in patients with cTTP. The application was awarded a Rare Pediatric Disease Priority Review Voucher and granted Priority Review, Fast Track, and Orphan designations.¹

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research.¹ “Without treatment, cTTP is ultimately fatal. Today’s approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

A rare blood clotting disorder, cTTP is caused by a mutation in the ADAMTS13 gene responsible for making an enzyme that regulates blood clotting. A deficiency in this enzyme causes blood clots to form in the small blood vessels throughout the body.¹

A purified recombinant form of the ADAMTS13 enzyme responsible for regulating blood clotting, Adzynma provides targeted therapy to address an unmet medical need in patients with thrombotic thrombocytopenic purpura by replacing the missing or deficient ADAMTS13 enzyme. It is the first and only recombinant ADAMTS13 protein in development, including a phase 1 study and a pair of ongoing phase 3 studies for use in cTTP. Along with cTTP, Adzynma is also being investigated in immune-mediated TTP and sickle cell disease, with phase 2b and phase 1 trials ongoing, respectively.²

According to the release, the efficacy of Adzynma in the prophylactic treatment of cTTP was evaluated in 46 patients who were randomly assigned to receive 6 months of treatment with either Adzynma or plasma-based therapies, then crossed over to the other treatment for 6 months. Its efficacy as a prophylactic treatment was demonstrated based on the incidence of thrombotic thrombocytopenic purpura events and manifestations, as well as the incidence of the need for supplemental doses. Its efficacy as an on-demand enzyme replacement therapy was evaluated based on the proportion of acute thrombotic thrombocytopenic purpura events responding to Adzynma in both the prophylactic and the on-demand cohorts throughout the duration of the study.¹

Takeda announced favorable interim results of the phase 3 trial on June 25, 2023, which showed no patient had an acute thrombotic thrombocytopenic purpura event while receiving Adyznma prophylactic treatment. Adyznma also reduced the incidence of thrombocytopenia by 60% compared to plasma-based therapy and demonstrated a favorable safety and tolerability profile, with treatment-emergent adverse events reported in 10.3% of patients ages 12-68 receiving Adyznma compared to 50% of patients receiving plasma-based therapy.²

All acute and subacute thrombotic thrombocytopenic purpura events resolved after treatment with either Adzynma or plasma-based therapies. The most common side effects associated with Adzynma included headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness, and vomiting. During the clinical studies, no adverse events were observed during the administration of Adzynma.¹

“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, MD, professor of internal medicine at the Wexner Medical Center at The Ohio State University and co-director at the US Thrombotic Microangiopathy Alliance.³ “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.”

References:

1. US Food and Drug Administration. FDA Approves First Treatment for Patients with Rare Inherited Blood Clotting Disorder. Press Announcements. November 9, 2023. Accessed November 9, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-rare-inherited-blood-clotting-disorder
2. Takeda Pharmaceuticals. Pivotal Phase 3 Data Presented at ISTH 2023 Congress Spotlight TAK-755 Prophylaxis for Patients with Congenital Thrombotic Thrombocytopenic Purpura (cTTP). Newsroom. June 25, 2023. Accessed November 9, 2023. https://www.takeda.com/newsroom/newsreleases/2023/pivotal-phase-3-data-presented-at-isth-2023-congress/
3. Takeda Pharmaceuticals. 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). Newsroom. November 9, 2023. Accessed November 9, 2023. https://www.takeda.com/newsroom/newsreleases/2023/takeda-adzynma-approved-by-fda-as-the-first-and-only-recombinant-adamts13-enzyme-replacement-therapy-for-the-treatment-of-congenital-thrombotic-thrombocytopenic-purpura/