- cTTP is an Ultra-rare Blood Clotting Disorder Associated
with Life-Threatening Acute Events and Debilitating Chronic
Symptoms
- ADZYNMA (apadamtase alfa /cinaxadamtase alfa) is the First
and Only Recombinant ADAMTS13 Enzyme Replacement Therapy for People
with cTTP
Takeda (TSE: 4502/NYSE:TAK) today announced that the Japanese
Ministry of Health, Labour and Welfare has approved the use of
ADZYNMA (apadamtase alfa /cinaxadamtase alfa) for the treatment of
congenital thrombotic thrombocytopenic purpura (cTTP) for
individuals 12 years of age and older.1 ADZYNMA is the first and
only approved recombinant ADAMTS13 protein designed to address an
unmet medical need in people with cTTP by replacing the deficient
ADAMTS13 enzyme.
cTTP is an ultra-rare, chronic blood clotting disorder caused by
a deficiency in the ADAMTS13 enzyme.2 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.2,3,4 When left untreated, acute TTP events have a
mortality rate of >90%.2,4
“The approval of ADZYNMA is an important milestone for people
living with cTTP in Japan, who had limited treatment options and
now have the first treatment option specifically approved to treat
this ultra-rare condition,” said Yasushi Kajii, Head, R&D Japan
Region at Takeda. “Developing innovative treatments that make a
difference in the lives of patients is at the heart of what we do.
With this approval, we are proud to support the cTTP community with
new possibilities and continue our 70-plus year commitment to the
rare disease community.”
The approval is supported by the totality of the evidence
provided from an interim analysis of efficacy, pharmacokinetic,
safety and tolerability data from the first randomized, controlled,
open-label, crossover Phase 3 trial in cTTP patients ages 12-68,
(281102 NCT03393975) which includes five Japanese patients and
supported by long-term safety and efficacy data from a continuation
study (TAK-755-3002 NCT04683003).5 At the time of interim analysis,
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) during the
Phase 3 study-controlled comparison periods 1 and 2.6
Treatment-emergent adverse events (TEAEs) assessed as
treatment-related during periods 1 and 2 were reported in 10.3% of
patients receiving ADZYNMA compared to 50% of patients receiving
plasma-based therapy.6 TEAEs observed in ADZYNMA group were
constipation, ADAMTS13 activity abnormal, headache, pruritus, and
hypertension (1 subject each). In Period 3, the incidence of TEAEs
was 2.8% (1/36) in this drug group: nausea and headache (1 subject
each).6
This approval does not result in any changes to Takeda’s
consolidated forecast for the fiscal year ending March 31, 2024
(FY2023).
ABOUT ADZYNMA (apadamtase alfa /cinaxadamtase alfa)
ADZYNMA (apadamtase alfa /cinaxadamtase alfa) is a human
recombinant “A disintegrin and metalloproteinase with
thrombospondin motifs 13” ADAMTS13 (rADAMTS13) indicated for
congenital thrombotic thrombocytopenic purpura (cTTP) in Japan.1
ADZYNMA can be used for prophylactic or on-demand enzyme
replacement therapy (ERT) in patients 12 years of age and
older.
ADZYNMA is also approved by the U.S. Food and Drug
Administration (FDA) for the prophylactic and on-demand treatment
of adult and pediatric patients with congenital thrombotic
thrombocytopenic purpura (cTTP).7
ADZYNMA was previously granted Orphan Drug Designation (ODD) by
the U.S. FDA for the treatment and prevention of TTP, including its
acquired idiopathic and secondary forms, and by the European
Medicines Agency (EMA) and Japan’s Ministry of Health, Labour and
Welfare (MHLW) for the treatment of TTP.
ADZYNMA (apadamtase alfa /cinaxadamtase alfa) Product
Overview in Japan
Brand Name
ADZYNMA Intravenous Injection 1500
Generic Name
apadamtase alfa /cinaxadamtase alfa
Indications
Congenital thrombotic thrombocytopenic
purpura (cTTP)
Dosage and Administration
This drug should be reconstituted with 5
mL of the supplied solvent, and the reconstituted solution should
be slowly injected intravenously at a rate of 2~4 mL/min.
For prophylactic treatment
The usual dosage for adults and children
aged ≥ 12 years is 40 IU/kg (body weight) every other week. A dose
of 40 IU/kg (body weight) may be administered once weekly depending
on the dose and regimen of prior therapy or clinical response.
For on-demand treatment
The usual initial dosage for adults and
children aged ≥ 12 years is 40 IU/kg (body weight) on Day 1 as the
initial dose for measures such as management of thrombotic
thrombocytopenic purpura symptoms. Patients will receive 20 IU/kg
(body weight) daily on Day 2 and 15 IU/kg (body weight) daily from
Day 3 until Day 2 after resolution of symptoms.
ABOUT cTTP
cTTP is an ultra-rare, chronic and debilitating clotting
disorder associated with life-threatening acute events and
debilitating chronic symptoms, or TTP manifestations, which can
include thrombocytopenia, microangiopathic hemolytic anemia,
headache and abdominal pain.8,9 TTP has an estimated prevalence of
2-6 cases/million, though the true prevalence is unknown. The
inherited form of the disease, cTTP, accounts for ≤5% of TTP
patients.9,10,11 It develops due to deficiency in ADAMTS13, a von
Willebrand factor (VWF) cleaving protease, which results in the
accumulation of ultra-large VWF multimers in the blood.8 The
accumulation of ultra-large VWF multimers leads to uncontrolled
platelet aggregation and adhesion.3,9 This can lead to abnormal
clotting in the small blood vessels of the body and is associated
with microangiopathic hemolytic anemia and low platelet levels
(thrombocytopenia).3
cTTP has both acute and chronic manifestations (including stroke
and cardiovascular disease) and when left untreated, acute TTP
events have a mortality rate of >90%.3,11 cTTP can also cause
ongoing widespread organ damage and other co-morbidities resulting
from an ADAMTS13-deficient state.4,9,12,13
Important Safety Information
Apadamtase alfa /cinaxadamtase alfa is contraindicated in
patients with a history of hypersensitivity to any of the
ingredients of this drug.
Hypersensitivity Reactions: Allergic-type
hypersensitivity, including anaphylactic reactions, may occur with
apadamtase alfa /cinaxadamtase alfa. Patients should be educated
about early signs of hypersensitivity such as tachycardia, chest
tightness, wheezing and/or acute respiratory distress, hypotension,
generalized urticaria, pruritus, rhinoconjunctivitis, angioedema,
lethargy, nausea, vomiting, paresthesia, and restlessness. If signs
and symptoms of severe allergic reactions occur, immediately
discontinue administration of apadamtase alfa /cinaxadamtase alfa
and provide appropriate supportive care.
Immunogenicity: There is a potential for immunogenicity
with apadamtase alfa /cinaxadamtase alfa. Patients may develop
neutralizing antibodies to ADAMTS13, which could potentially result
in a decreased or lack of response to ADAMTS13. Patients may
develop antibodies to host cell proteins which could potentially
result in adverse reactions. There are no data on immunogenicity
with apadamtase alfa /cinaxadamtase alfa or to host cell proteins
in previously untreated patients (subjects naïve to plasma-based
products).
Adverse Reactions: The most commonly observed adverse
reactions (>5% of subjects) associated with apadamtase alfa
/cinaxadamtase alfa are headache, diarrhea, migraine, abdominal
pain, nausea, upper respiratory tract infection, dizziness and
vomiting.
Use in Specific Populations: This drug should be
administered to pregnant women or possibly pregnant women only if
the expected therapeutic benefits outweigh the possible risks
associated with treatment.
To report SUSPECTED ADVERSE REACTIONS, contact Takeda
Pharmaceuticals U.S.A, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or
FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
Please see full Prescribing Information,
including information for patients.
ABOUT TAKEDA
Takeda is focused on creating better health for people and a
brighter future for the world. We aim to discover and deliver
life-transforming treatments in our core therapeutic and business
areas, including gastrointestinal and inflammation, rare diseases,
plasma-derived therapies, oncology, neuroscience and vaccines.
Together with our partners, we aim to improve the patient
experience and advance a new frontier of treatment options through
our dynamic and diverse pipeline. As a leading values-based,
R&D-driven biopharmaceutical company headquartered in Japan, we
are guided by our commitment to patients, our people and the
planet. Our employees in approximately 80 countries and regions are
driven by our purpose and are grounded in the values that have
defined us for more than two centuries. For more information, visit
www.takeda.com.
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Medical information
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prescription drugs including the ones under development.
References:
- ADZYNMA Package Insert in Japan.
- Van Dorland H et al. Haematologica. 2019;104:2107-16.
- Chiasakul T and Cuker A. Am Soc Hematol.
2018;2018(1):530–538.
- Joly BS et al., Blood. 2017;129(21):2836–2846.
- ClinicalTrials.gov A Study of TAK-755 in Participants with
Congenital Thrombotic Thrombocytopenic Purpura Available at:
https://clinicaltrials.gov/ct2/show/NCT04683003. Accessed March
2024.
- Scully M, et al. Phase 3 prospective, randomized, controlled,
open-label, multicenter, crossover study of recombinant ADAMTS13 in
patients with congenital thrombotic thrombocytopenic purpura. ISTH
2023 Congress; June 24-28, 2023. Abstract OC 14.1.
- ADZYNMA (ADAMTS13, recombinant-krhn) Prescribing Information;
2023.
- Alwan F, et al., Blood. 2019;133:1644-51.
- Kremer Hovinga JA, et al. Nat Rev Dis Primers.
2017;3:17020.
- Kremer Hovinga JA, George JN. Hereditary Thrombotic
Thrombocytopenic Purpura. N Engl J Med.
2019;381(17):1653-1662.
- Orpha.net. Congenital thrombotic thrombocytopenic purpura.
Available at:
https://www.orpha.net/en/disease/detail/93583?name=Congenital%20thrombotic%20thrombocytopenic%20purpura&mode=name.
Accessed March 2024.
- Zheng XL et al. J Thromb Haemost. 2020;18(10):2486-95.
- Sukumar S, et al. J Clin Med. 2021;10:536.
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version on businesswire.com: https://www.businesswire.com/news/home/20240325490780/en/
MEDIA:
Japanese Media Shigeyuki Matsui
shigeyuki.matsui@takeda.com
U.S. and International Media Megan Ostrower
megan.ostrower@takeda.com
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