OSAKA, Japan & CAMBRIDGE, Mass. - Thursday, 05. January 2023
- Results are From First and Only Phase 3 Trial in cTTP, an Ultra-Rare Disease with Limited Treatment Options
- cTTP is Caused by a Deficiency in ADAMTS13 Protease; 1 TAK-755 Is Designed to Replace Missing or Deficient ADAMTS13 Enzyme2
- Takeda Plans to Seek Marketing Authorization for TAK-755 as the First ADAMTS13 Replacement Therapy for the Treatment of cTTP
(BUSINESS
WIRE) --Takeda (TSE:4502/NYSE:TAK) today announced that the totality of
evidence from a pre-planned interim analysis of a pivotal Phase 3 study
supports the efficacy and safety of TAK-755 as enzyme replacement
therapy for congenital thrombotic thrombocytopenic purpura (cTTP). cTTP
is an ultra-rare sub-type of thrombotic thrombocytopenic purpura (TTP), a
rare, chronic and debilitating blood clotting disorder caused by a
deficiency in ADAMTS13 protease.1,3 Acute TTP has a mortality rate of
>90%, if left untreated.4
The trial was designed to evaluate
the clinical benefit of TAK-755 across multiple clinically relevant
endpoints and based on the totality of the evidence provided by
efficacy, pharmacokinetic, safety and tolerability data.5 This approach
was discussed with global regulatory agencies. The study evaluated
TAK-755 compared to plasma-based therapies, which are the current
standard of care (SoC), in a randomized cross-over study. The interim
results showed that TAK-755 reduced the incidence of thrombocytopenia
events by 60% (95% Confidence Interval, 30%-70%), an important marker of
disease activity in cTTP, as compared to SoC. The proportion of
subjects experiencing adverse events determined to be related to the
treatment was substantially lower among subjects during treatment with
TAK-755 (8.9%) compared to that while receiving SoC therapy (47.7%).
Based
on these data from the Phase 3 interim analysis, Takeda aims to seek
marketing authorization for TAK-755 as the first recombinant ADAMTS13
(rADAMTS13) replacement therapy for cTTP, a disorder with considerable
unmet patient need.
“We are committed to advancing treatment
options for those living with cTTP, who currently have no therapies
approved specifically to manage their condition,” said Daniel Curran,
M.D., Head, Rare Genetics & Hematology Therapeutic Area Unit at
Takeda. “The results of the trial are very encouraging, and we look
forward to continuing to engage with global regulatory bodies with the
aim of bringing TAK-755 to patients as rapidly as possible.”
Takeda plans to submit the results of this interim analysis for presentation at an upcoming scientific meeting.
In
addition to announcing these results, Takeda indicated that the
December 22, 2022, edition of the New England Journal of Medicine (NEJM)
included two case reports written and submitted by two physicians who
requested compassionate use of TAK-755 to treat patients who were facing
critical health complications related to cTTP. The case reports are
available on NEJM’s website.
TAK-755 is also being investigated
in a Phase 2 study to evaluate the pharmacokinetics, safety and efficacy
of rADAMTS13 in immune-mediated TTP (iTTP).6
Results from the
interim analysis of the Phase 3 study have no impact on the full year
consolidated reported forecast for the fiscal year ending March 31, 2023
(Fiscal Year 2022).
ABOUT TAK-755
TAK-755 is the first
and only recombinant ADAMTS13 protein in development. It provides
targeted therapy to address an unmet medical need in patients with
thrombotic thrombocytopenic purpura (TTP), by replacing the missing or
deficient ADAMTS13 enzyme.7
The TAK-755 cTTP clinical development
program includes one first-in-human, Phase 1 study, 281101
(NCT02216084),8 and two Phase 3 studies: a pivotal Phase 3 study, Study
281102 (NCT03393975), and one Phase 3b continuation study, Study
TAK-755-3002 (NCT04683003).5,9 TAK-755 is also being investigated in
immune-mediated TTP (iTTP) and sickle cell disease, with Phase 2
(NCT03922308) and Phase 1 (NCT03997760) trials ongoing, respectively,
and due to provide data in 2023.6,10
TAK-755 was granted Orphan
Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA)
for the treatment (ODA-08-2622) and prevention (ODA-08-2652) of TTP
including its congenital, 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 (EU/3/08/588). The
FDA has also granted TAK-755 Fast Track Designation (FTD) for the
treatment, prevention, and routine prophylaxis of acute episodes of TTP
in patients with hereditary (congenital) ADAMTS13 deficiency.
ABOUT cTTP
cTTP
is an ultra-rare, chronic, and debilitating blood clotting disorder
associated with life-threatening acute episodes and debilitating chronic
symptoms.1,3 cTTP is a sub-type of TTP that has an estimated prevalence
of 2-6 cases/million,11 with cTTP accounting for ≤5% of patients with
TTP.12,13 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.1 The accumulation of ultra-large
VWF multimers leads to uncontrolled platelet aggregation and
adhesion.3,14 This can lead to abnormal clotting in the small blood
vessels of the body and is associated with hemolytic anemia and low
platelet levels (thrombocytopenia).14
cTTP has both acute and
chronic manifestations (including stroke and cardiovascular disease) and
is associated with a significant disease burden. Patients’ quality of
life and lifespan are significantly reduced compared to the general
population, due to serious, ongoing widespread organ damage and other
co-morbidities resulting from an ADAMTS13-deficient state.3,12,15,16
rADAMTS13 is a novel investigational therapeutic approach for cTTP.17
The
current standard of care for cTTP is plasma therapy,16 which is
insufficient in restoring ADAMTS13, time-consuming, and costly.7,18,19
About Takeda
Takeda
is a global, values-based, R&D-driven biopharmaceutical leader
headquartered in Japan, committed to discover and deliver
life-transforming treatments, guided by our commitment to patients, our
people and the planet. Takeda focuses its R&D efforts on four
therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience,
and Gastroenterology (GI). We also make targeted R&D investments in
Plasma-Derived Therapies and Vaccines. We are focusing on developing
highly innovative medicines that contribute to making a difference in
people’s lives by advancing the frontier of new treatment options and
leveraging our enhanced collaborative R&D engine and capabilities to
create a robust, modality-diverse pipeline. Our employees are committed
to improving quality of life for patients and to working with our
partners in health care in approximately 80 countries and regions. For
more information, visit https://www.takeda.com.
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_______________________
1 Alwan F, et al., Blood. 2019;133:1644–51
2 Kopić A, et al., J Thromb Haemost. 2016;14(7):1410-1419. doi:10.1111/jth.13341
3 Kremer Hovinga JA, et al., Nat Rev Dis Primers. 2017;3:17020
4 Van Dorland H et al., Haematologica. 2019;104:2107-16
5
ClinicalTrials.gov A Study of BAX 930 in Children, Teenagers, and
Adults Born With Thrombotic Thrombocytopenic Purpura (TTP). Available
at: https://clinicaltrials.gov/ct2/show/NCT03393975 Last accessed
December 2022
6 ClinicalTrials.gov Study of rADAMTS-13 (SHP655)
in the Treatment of Participants With Acquired Thrombotic
Thrombocytopenic Purpura (aTTP) (SOAR-HI) Available at:
https://clinicaltrials.gov/ct2/show/NCT03922308 Last accessed December
2022
7 Scully M et al. Blood. 2017;130:2055-63
8
ClinicalTrials.gov Phase 1 Dose Escalation, Single Dose Study to Assess
Safety and Pharmacokinetics of BAX930 in Hereditary Thrombotic
Thrombocytopenic Purpura (TTP) Available at:
https://clinicaltrials.gov/ct2/show/NCT02216084 Last accessed December
2022
9 ClinicalTrials.gov A Study of TAK-755 in Participants With
Congenital Thrombotic Thrombocytopenic Purpura Available at:
https://clinicaltrials.gov/ct2/show/NCT04683003 Last accessed December
2022
10 ClinicalTrials.gov A Study of SHP655 (rADAMTS13) in
Sickle Cell Disease (RAISE) Available at: A Study of SHP655 (rADAMTS13)
in Sickle Cell Disease - Full Text View - ClinicalTrials.gov Last
accessed December 2022
11 Zheng XL et al., J Thromb Haemost. 2020;18(10):2486-95
12 Sukumar S, et al. J Clin Med 2021;10:536
13 Mariotte E, et al. Lancet Haematol 2016;3:e237–45
14 Chiasakul T and Cuker A. Am Soc Hematol. 2018;2018(1):530–538
15 Joly BS et al., Blood. 2017;129(21):2836–2846
16 Zheng XL et al., J Thromb Haemost. 2020;18:2503-12
17
Royal College of Pathologists Bulletin 200 October 2022. Available at:
https://www.rcpath.org/profession/publications/college-bulletin/october-2022/thrombotic-thrombocytopenic-purpura-past-present-and-future.html
Last accessed December 2022
18 Blombery P, Scully M. J Blood Med. 2014;5:15-23. Published 2014 Feb 5. doi:10.2147/JBM.S46458
19
Oladapo A et al., ISTH abstract PB1582. Available at:
https://academy.isth.org/isth/2019/melbourne/264771/abiola.oladapo.cost.of.illness.28coi29.of.congenital.thrombotic.thrombocytopenic.html?f=listing%3D6%2Abrowseby%3D8%2Asortby%3D2%2Atopic%3D21422
Last accessed December 2022
C-ANPROM/INT//8486
Date of Preparation: JAN 2023
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Contacts
Japanese Media
Jun Saito
jun.saito@takeda.com
+81 (0) 3-3278-2325
U.S. and International Media
Megan Ostrower
megan.ostrower@takeda.com
+1 772-559-4924