CAMBRIDGE, Mass. & OSAKA, Japan-Monday 8 July 2019 [ AETOS Wire ]
- Updated
results from the Phase IIIb/IV PROPEL Study show that pharmacokinetic
(PK)-driven dosing may be used to achieve FVIII target trough levels of
8–12%; and that selecting a patient-appropriate target FVIII level plus
adjusting a dosing regimen to that patient’s PK characteristics, can
improve the overall PK profile and may enhance outcomes, with no adverse
event profile change – thus reinforcing the importance of PK-guided
dosing and the potential benefit of personalized prophylaxis with
ADYNOVATE1
- Data
presented alongside 47 other ISTH 2019 presentations showcasing the
latest developments from Takeda’s hematology gene therapy pipeline and
leading Factor portfolio
- Takeda’s
robust presence at ISTH underscores its commitment to progressing
scientific advancements for the bleeding disorders community
(BUSINESS WIRE) -- Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”),
R&D-driven, global biopharmaceutical company with a leadership
position in rare diseases, has today announced updated results from its
phase IIIb/IV clinical trial for ADYNOVATE®[Antihemophilic
Factor (Recombinant), PEGylated] at the 27th Annual International
Society on Thrombosis and Haemostasis Congress (ISTH), in Melbourne,
Australia. The PROPEL study is a PROspective, randomized, multi-center study comparing the safety and efficacy of ADYNOVATE following PK-guided prophylaxis targeting two different Factor Eight (FVIII) trough activity Levels in subjects with severe hemophilia A.
The
latest results of the landmark PROPEL study show that ADYNOVATE
prophylaxis in severe hemophilia A patients may enhance a patient’s PK
profile - by targeting FVIII trough levels of 8–12% (elevated
prophylaxis arm, ELE) as compared with 1–3% (reference prophylaxis arm,
REF). This represents a clinically meaningful trend towards more
patients experiencing zero bleeds [62% ELE versus 42% REF, respectively;
p=0.0545].1 Patients randomized to the 8-12% target group also saw a:
- Reduced mean total annualized bleed rate (ABR); (1.6 ELE versus 3.6 REF, respectively).
- Reduced mean spontaneous joint ABR (0.5 ELE versus 2.0 REF)
The
data supports the view that patients may benefit from PK-driven dosing
that targets FVIII trough levels of 8–12%. The safety findings from this
latest update were also comparable and consistent with previous
ADYNOVATE trials.1,2 Ongoing analyses will further
characterize the relationship between PK-tailored dosing of ADYNOVATE
FVIII levels and bleeding events.
Adapting
the dosing regimen for an individual patient, guided by that patient’s
individual PK characteristics, has great potential – for managing
patients with hemophilia A, particularly those desiring greater bleed
protection.1
“These
results, for the first time, provide proof of concept that targeting
higher FVIII troughs can benefit severe hemophilia A patients with no
adverse event profile change. The next step will be to characterize the
relationships between pharmacokinetic profiles, FVIII activity levels
and bleeding events, so that we can understand more about the optimal
approach for personalized prophylaxis in hemophilia A and help more
patients reach zero bleeds,” said PD Dr. med. Robert Klamroth, Head of
the Department of Internal Medicine Angiology and Coagulation Disorders
and Director of the Comprehensive Care Haemophilia Treatment Center and
the Haemostasis and Thrombosis Unit at the Vivantes Klinikum in Berlin,
Germany.
“The
PROPEL data confirm the critical role of FVIII replacement therapy and
demonstrate that with PK-guided prophylaxis with ADYNOVATE
individualized FVIII levels of 8–12% can be reliably achieved to improve
the outcomes for some patients. Hence, the study reinforces Takeda’s
leadership in advancing treatment for hemophilia A, which also includes a
comprehensive gene therapy clinical trial program,” said Dr. med.
Wolfhard Erdlenbruch, Vice President Head of Global Medical Hematology,
Takeda. “ISTH provides a great opportunity for us to demonstrate our
ongoing commitment to the hemophilia community and we are excited to be
sharing several important updates from our R&D portfolio this week.”
In
addition to PROPEL, Takeda are presenting 47 other data updates across
the hematology portfolio. Most notably, 14 presentations will unveil
some of the foundational work being carried out within the Takeda
Hematology gene therapy pipeline, looking at ways to help hemophilia
patients naturally produce factor VIII or IX, in order to eliminate or
experience fewer bleeding episodes.
About the PROPEL Study1,2
The
PROPEL study evaluated the safety and efficacy of ADYNOVATE in
PK-guided prophylaxis targeting two different FVIII trough levels in
previously treated patients with severe hemophilia A.
Methods:
Eligible subjects had FVIII activity <1%, annualized bleed rate
(ABR) ≥2, and transitioned from a previous SHP660 (ADYNOVATE) study or
were 12–65 years old with ≥150 exposure days to plasma-derived or
recombinant FVIII. After initial PK assessments, subjects were
randomized to receive 12 months of PK-guided prophylaxis targeting FVIII
trough levels of 1–3% (REF) or 8–12% (ELE) (1st 6 months: dose adjustment period). Primary outcome was the % of subjects with a total ABR=0 (all bleeds) during the 2nd 6-month
study period. Secondary outcomes included total ABR, spontaneous ABR
and joint ABR (AJBR) (all bleeds), SHP660 consumption and adverse events
(AEs). 1
Results:
Overall, 115 male subjects (57, REF; 58, ELE) received ≥1 prophylactic
SHP660 dose. Median (range) age was 29 (12–61) years; 100 subjects (52,
REF; 48, ELE) completed the study. During the 2nd 6 months,
the multiple imputations (MI) estimate for REF vs ELE was 42% vs 62%
(p=0.0545) for total ABR=0, 60% vs 76% (p=0.1006) for spontaneous ABR=0,
and 65% vs 85% (p=0.0260) for spontaneous AJBR=0. Mean (SD), median
(IQR) total ABRs for the 2nd 6-month period: 3.6 (7.5), 2.0
(4.0) REF; 1.6 (3.4), 0 (2.0) ELE. Overall AEs and SAEs occurred in REF
vs ELE: 60% vs 62% and REF vs ELE: 5% vs 7% of the subjects, with 1 SAE
in an 8–12% target subject considered related to SHP660: a transient 0.6
BU inhibitor without evidence of anti-FVIII binding, which resolved
before study end. AE profiles were comparable and consistent with
previous SHP660 trials.1
About ADYNOVATE/ADYNOVI
ADYNOVATE [Antihemophilic
Factor (Recombinant), PEGylated] was first approved by the Food and
Drug Administration (FDA) in the U.S. followed by approval in Japan,
Canada, and Colombia, and is approved as ADYNOVI® in the 28
Member States of the European Union (EU) as well as Iceland,
Liechtenstein, Norway and Switzerland. In Europe ADYNOVI is approved for
the treatment and prophylaxis of bleeding in patients 12 years and
above with hemophilia A.
ADYNOVI SAFETY INFORMATION FOR EUROPE3
Please
consult the ADYNOVI Summary of Product Characteristics (SmPC) before
prescribing, particularly in relation to dosing and treatment
monitoring.
Contraindications
Hypersensitivity
to the active substance, to the parent molecule octocog alfa or to any
of the excipients listed in the SmPC. Known allergic reaction to mouse
or hamster protein.
Special warnings and precautions for use
The
medicinal product contains traces of mouse and hamster proteins. If
symptoms of hypersensitivity occur, patients should be advised to
discontinue use of the medicinal product immediately and contact their
physician. Patients should be informed of the early signs of
hypersensitivity reactions including hives, generalised urticaria,
tightness of the chest, wheezing, hypotension, and anaphylaxis.
The
formation of neutralising antibodies (inhibitors) against factor VIII
is a known complication in the management of individuals with
haemophilia A. These inhibitors are usually IgG immunoglobulins directed
against the factor VIII procoagulant activity, which are quantified in
Bethesda Units (BU) per ml of plasma using the modified assay.
In
general, all patients treated with coagulation factor VIII should be
carefully monitored for the development of inhibitors by appropriate
clinical observations and laboratory tests. If the expected factor VIII
activity plasma levels are not attained, or if bleeding is not
controlled with an appropriate dose, testing for factor VIII inhibitor
presence should be performed.
After reconstitution this medicinal product contains 0.45 mmol sodium (10 mg) per vial.
Adverse Reactions
|
Common (Greater-than or equal to 1/100 to <1/10)
|
Headache, Diarrhea, Nausea, Rash
|
|
Uncommon (Greater-than or equal to 1/1000 to
<1/100)
|
Factor VIII inhibition in previously-treated patients
(PTPs), Hypersensitivity, Flushing
|
For more information, please refer to the ADYNOVI Summary of Product Characteristics here.
For US specific safety information, please refer to the ADYNOVATE US Prescribing Information here.
About Hemophilia
Hemophilia
is a challenging chronic disease that causes longer-than-normal
bleeding due to absent or deficient clotting factor in the blood.4 Hemophilia A is more common than hemophilia B;4 hemophilia A affects about 158,225 people, whereas hemophilia B affects about 31,247 people worldwide.5
People
with hemophilia, working closely with their healthcare professionals,
can live healthy lives with proper care and adequate treatment.6 Treatment
regimens typically include on-demand and/or regular prophylactic
infusions of factor replacement therapy to control or prevent the risk
of bleeding.4,7
About Takeda Hematology
Following
its recent acquisition of Shire, Takeda is a leader in hemophilia with
the longest heritage and market-leading portfolio, backed by established
safety and efficacy profiles with decades of real world experience. We
have 70+ years driving innovation for patients8 and a broad
portfolio of 11 products across nine hemophilia indications. Our
experience as leaders in hematology means we are well prepared to meet
today’s needs as we pursue future developments in the care of bleeding
disorders. Together with the hematology community, we are raising
expectations for the future, including earlier diagnosis, earlier and
full protection against bleeds, and more personalized patient care.
About Takeda Pharmaceutical Company Limited
Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a
global, values-based, R&D-driven biopharmaceutical leader
headquartered in Japan, committed to bringing Better Health and a
Brighter Future to patients by translating science into
highly-innovative medicines.
Takeda
focuses its R&D efforts on four therapeutic areas: Oncology,
Gastroenterology (GI), Rare Diseases and Neuroscience. 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.
References
- Klamroth R, Windyga J, Radulescu V, et al., PK-guided rurioctocog alfa pegol prophylaxis in patients with severe hemophilia A targeting two FVIII trough levels: results from the phase 3 PROPEL Study. Presented at ISTH 2019 (International Society on Thrombosis and Haemostasis (ISTH) Biennial Congress. July 6-10, 2019. Abstract #A-1052-0038-01311.
- Klamroth R, Windyga J, Radulescu V, et al., Results of a phase 3, randomized, multicenter study of RURIOCTOCOG ALFA PEGOL PK-guided prophylaxis targeting 2 FVIII trough levels in patients with severe Hemophilia A (propel study). Presented at European Association of Haematology and Allied Disorders (EAHAD) February 2019. Abstract #255.
- Shire Pharmaceuticals Group. Shire granted EU marketing authorization for ADYNOVI (Antihemophilic Factor (Recombinant). PEGylated) for adults and adolescents with Hemophilia A. 2018. Available here: https://globenewswire.com/news-release/2018/01/15/1289070/0/en/Shire-granted-EU-marketing authorization-for-ADYNOVI-Antihemophilic-Factor-Recombinant-PEGylated-for-adults-and-adolescents-with Hemophilia-A.html Last accessed April 2019.
- World Federation of Hemophilia. “What is hemophilia?” World Federation of Hemophilia website. http://www.wfh.org/en/page.aspx?pid=646. Last Accessed June 2019.
- World Federation of Hemophilia. Report on the Annual Global Survey 2017. World Federation of Hemophilia website. http://www1.wfh.org/publications/files/pdf-1714.pdf. Last Accessed June 2019.
- World Federation of Hemophilia. “About Bleeding Disorders: Treatment.” World Federation of Hemophilia website. https://www.wfh.org/en/page.aspx?pid=642. Last Accessed June 2019.
- National Hemophilia Foundation. “Hemophilia A”. National Hemophilia Foundation website.https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A. Last Accessed June 2019.
- Shire Website. Standards of Care for Hemophilia. Website: https://www.shire.com/who-we-are/how-weoperate/policies-and-positions/standards-of-care-for-hemophilia Last Accessed April 2019.
View source version on businesswire.com: https://www.businesswire.com/news/home/20190707005038/en/
Contacts
Media Contacts:
Japanese Media
Kazumi Kobayashi
kazumi.kobayashi@takeda.com
+81 (0) 3-3278-2095
Media outside Japan
Tsuyoshi Tada
tsuyoshi.tada@takeda.com
+1 (617) 551-2933
Media outside Japan
Linda Calandra
linda.calandra1@takeda.com
+1 (617) 301-2092
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