Adzynma Approved for Congenital Thrombotic Thrombocytopenic Purpura

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

Congenital thrombotic thrombocytopenic purpura (cTTP) results from a deficiency in  ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin motifs 13), a von Willebrand factor (VWF) cleaving protease. This leads to an accumulation of ultra-large VWF multimers in the blood and uncontrolled platelet aggregation and adhesion. Adzynma is a purified recombinant form of the ADAMTS13 protein designed to replace the missing or deficient ADAMTS13 enzyme.

The approval was based on data from a randomized, crossover phase 3 study (ClinicalTrials.gov Identifier: NCT03393975) that evaluated the safety and efficacy of prophylactic ERT with Adzynma in patients with cTTP. Study participants in the prophylaxis cohort (N=46) were randomly assigned to receive 6 months of treatment with either Adzynma or plasma based therapy in the first part of the trial (Period 1), and then crossed over to the other treatment for 6 months in the second part of the trial (Period 2). Thirty-five patients entered the 6-month single arm continuation period (Period 3).

There were no acute TTP events throughout the study among patients who received Adzynma. One acute TTP event occurred in a patient who received plasma-based therapy. Additionally, no subacute TTP events were reported among those who received Adzynma during Periods 1 and 2. Two patients receiving Adzynma had 2 subacute events of which one was treated with 4 supplemental doses. Four patients receiving plasma-based therapy had 5 subacute TTP events in Periods 1 and 2. A total of 7 supplemental doses were given to 3 of these patients.

The study also investigated the efficacy of on-demand ERT based on the proportion of acute TTP events that responded to Adzynma throughout the duration of the study. Patients were randomly assigned to receive on-demand treatment with Adzynma (n=2) or plasma-based therapy (n=3). Findings showed that all 6 acute TTP events resolved after treatment with either Adzynma or plasma based therapy.

“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,” said Spero R. Cataland, MD, professor of internal medicine at the Wexner Medical Center at The Ohio State University, co-director at the US Thrombotic Microangiopathy Alliance and Adzynma clinical trial investigator.

The most common adverse events reported with Adzynma were headache, diarrhea, migraine, abdominal pain, nausea, upper respiratory tract infection, dizziness and vomiting. The prescribing information also includes warnings and precautions related to hypersensitivity and immunogenicity.

Adzynma is administered intravenously once every other week for prophylactic ERT and once daily for on-demand ERT. The product is supplied as a lyophilized powder in single-dose vials containing nominally 500 or 1500 international units and is expected to be available in December 2023.

References

1. US Food and Drug Administration. FDA approves first treatment for patients with rare inherited blood clotting disorder. November 9, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-rare-inherited-blood-clotting-disorder.
2. Takeda’s Adzynma (ADAMTS13, recombinant-krhn) approved by US FDA as the first and only recombinant ADAMTS13 enzyme replacement therapy for the treatment of congenital thrombotic thrombocytopenic purpura (cTTP). News release. Takeda. November 9, 2023. https://www.businesswire.com/news/home/20231106845467/en/Takeda%E2%80%99s-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.
3. Adzynma. Package insert. Takeda; 2023. Accessed November 9, 2023. https://content.takeda.com/?contenttype=PI&product=ADZ&language=ENG&country=USA&documentnumber=1.

This article originally appeared on MPR