Perspectives
High-Cost Therapy Profile
December 15, 2023Detailed information about ADAMTS13, recombinant-krhn (Adzynma)
High-Cost Therapy Profile
ADAMTS13, recombinant-krhn (Adzynma)
Hematology/Enzyme Replacement Therapy
Intravenous (IV)
Takeda / Shire
Approved indications
Prophylactic or on-demand enzyme replacement therapy (ERT) in adult and pediatric patients with congenital thrombotic thrombocytopenic purpura (cTTP).
FDA approval timeline
Received Food and Drug Administration (FDA) approval November 9, 2023, ahead of the January 16, 2024 PDUFA date.
- Fast Track
- Orphan Drug
- Priority Review
- Rare Pediatric Disease (RPD)
Place in therapy
ADAMTS13, recombinant-krhn is a recombinant ‘A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13’ (ADAMTS13) protein that replaces missing or deficient ADAMTS13 enzymes in patients with cTTP.
- ADAMTS13, recombinant-krhn is the first targeted therapy for the prophylactic or on-demand treatment of cTTP
- In a phase 3 open-label study, treatment with ADAMTS13, recombinant-krhn led to zero acute thrombotic thrombocytopenic purpura (TTP) episodes and a reduced incidence of thrombocytopenia
- In its clinical trial, ADAMTS13, recombinant-krhn demonstrated clinically meaningful improvement in ADAMTS13 activity level compared to those treated with standard of care plasma-based therapy
- ADAMTS13, recombinant-krhn will address an unmet need for patients with cTTP and potentially transform the treatment landscape by providing an option that addresses the underlying cause of the disease
- ADAMTS13, recombinant-krhn is also being studied in patients with a diagnosis of immune-mediated TTP (iTTP) as well as sickle cell disease
Understanding your data
ADAMTS13, recombinant-krhn is a recombinant ADAMTS13 replacement therapy for patients with cTTP. It has demonstrated improvement in clinical symptoms related to cTTP. Clinical trials evaluating ADAMTS13, recombinant-krhn in cTTP are limited and include the following:
NCT03393975 – A phase 3, prospective, randomized, controlled, open-label, multicenter, 2 period crossover study with a single arm continuation evaluating the safety and efficacy of BAX 930 (rADAMTS13) in the prophylactic and on-demand treatment of subjects with severe cTTP (Upshaw-Schulman Syndrome [USS], hTTP)
NCT04683003 – A phase 3b, prospective, open-label, multicenter, single treatment arm, continuation study of the safety and efficacy of TAK-755 (rADAMTS13, also known as BAX 930/SHP655) in the prophylactic and on-demand treatment of subjects with severe cTTP (USS or hTTP)
Identification of patients would reflect the clinical trials criteria listed in the studies above, as well as diagnosis codes identified from claims data requiring among others:
Common Measurable Inclusion Criteria:
- Age: ≥ 0 and ≤70 years old**
- ICD-10 for congenital and hereditary thrombocytopenia purpura
Common Measurable Exclusion Criteria:
- Microangiopathic hemolytic anemia (including acquired TTP)**
**from clinical trial
| Category | Procedure codes |
| Congenital and hereditary thrombotic thrombocytopenic purpura (cTTP) | ICD-10: D69.42 |
| Other nonautoimmune hemolytic anemias (includes microangiopathic hemolytic anemia) | ICD-10: D59.4 |
| Thrombocytopenia, unspecified (includes acquired thrombocytopenia) | ICD-10: D69.6 |
Drug names are the property of their respective owners.
Clinical deep dive
Disease State Overview
Congenital thrombotic thrombocytopenic purpura (cTTP) is a blood clotting disorder that is caused by mutations in the ADAMTS13 gene. Patients with cTTP have a deficiency in the ADAMTS13 enzyme that is responsible for regulating the formation of blood clots. As a result, abnormal clotting in the blood vessels can occur causing acute disease exacerbations and/or chronic symptoms. Disease complications vary in severity and may include thrombocytopenia, hemolytic anemia, cardiovascular disease, organ damage, and stroke. Patients have > 90% mortality rate if left untreated.
Epidemiology
cTTP is an ultra-rare condition that affects < 1 in 1,000,000 individuals annually. The disease carries an autosomal recessive pattern of inheritance and typically presents in infancy or early childhood; however, development in adulthood can also occur sometimes manifesting during pregnancy or after infection or vaccination. There is a higher incidence in women than men, 2:1 respectively.
Treatment
There are no FDA approved treatments for patients with cTTP. The goal of therapy is to replace the ADAMSTS13 enzyme to prevent excessive blood clotting and subsequent disease complications. The standard of care for patients with cTTP is plasma-based therapy by infusion or plasma exchange. During pregnancy, prophylactic plasma transfusion is recommended otherwise a watch and wait strategy may be considered for asymptomatic patients.
Drug and clinical trial overview
The safety and efficacy of ADAMTS13, recombinant-krhn were evaluated in an open-label, phase 3 trial in 38 patients 0 to 70 years of age with a confirmed diagnosis of cTTP. During the crossover study, patients were randomized 1:1 to receive ADAMTS13, recombinant-krhn 40 IU/kg or plasma-based therapy either once weekly or every other week for the first 6 months, then both groups switched treatment arms for an additional 6 months. During the third 6 month period all patients were treated with ADAMTS13, recombinant-krhn. An interim analysis revealed that no acute TTP events occurred and the incidence of thrombocytopenia was reduced by 60% with the ADAMTS13, recombinant-krhn treatment group after a mean exposure of 13.2 months. Additionally, treatment emergent adverse events (TEAEs) occurred less frequently with ADAMTS13, recombinant-krhn than with plasma-based therapy (10.3% versus 50%, respectively) and no patients treated with the drug developed neutralizing antibodies. Data from the study also showed that patients treated with ADAMTS13, recombinant-krhn demonstrated 5 times higher activity level of ADAMTS13 after a single infusion compared to those treated with standard of care treatment. The ongoing phase 3b continuation study has demonstrated comparable results.
Pipeline (late stage development)
| Name | Manufacturer | Route of administration | Mechanism of action | Proposed/studied indication | Status |
| No published information at this time | |||||
References
- Adzynma [package insert]. Lexington, MA; Takeda; November 2023.
- ClinicalTrials.gov. A phase 3, prospective, randomized, controlled, open-label, multicenter, 2 period crossover study with a single arm continuation evaluating the safety and efficacy of BAX 930 (rADAMTS13) in the prophylactic and on-demand treatment of subjects with severe congenital thrombotic thrombocytopenic purpura (cTTP, Upshaw-Schulman Syndrome [USS], hereditary thrombotic thrombocytopenic purpura [hTTP]). Available at: https://clinicaltrials.gov/study/NCT03393975?intr=tak-755&rank=4. Accessed October 20, 2023.
- ClinicalTrials.gov. A phase 3b, prospective, open-label, multicenter, single treatment arm, continuation study of the safety and efficacy of TAK-755 (rADAMTS13, also known as BAX 930/SHP655) in the prophylactic and on-demand treatment of subjects with severe congenital thrombotic thrombocytopenic purpura (cTTP; Upshaw-Schulman Syndrome, or hereditary thrombotic thrombocytopenic purpura). Available at: https://clinicaltrials.gov/study/NCT04683003?intr=tak-755&rank=1. Accessed October 20, 2023.
- Congenital thrombotic thrombocytopenic purpura. Orphanet. Available at: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=93583. Accessed October 23, 2023.
- FDA approves first treatment for patients with rare inherited blood clotting disorder. November 9, 2023. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-rare-inherited-blood-clotting-disorder. Accessed November 9, 2023.
- Pivotal phase 3 data presented at ISTH 2023 Congress spotlight TAK-755 prophylaxis for patients with congenital thrombotic thrombocytopenic purpura (cTTP). Jun 25, 2023. Available at: https://www.takeda.com/newsroom/newsreleases/2023/pivotal-phase-3-data-presented-at-isth-2023-congress/. Accessed October 20, 2023.
- Scully M, Knobl P, Kentouche K, et al. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood. 2017; 130(19): 2055-2063.
- U.S. Food & Drug Administration grants priority review of TAK-755 for the treatment of congenital thrombotic thrombocytopenic purpura (cTTP). May 17, 2023. Available at: https://www.takeda.com/newsroom/newsreleases/2023/us-food-drug-administration-grants-priority-review-of-tak-755/. Accessed October 20, 2023.
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