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European Hematology Association
Annual Congress
June 13 – 16, 2019
Amsterdam, The Netherlands
The 24th Annual Congress covers every subspecialty in
hematology, with experts from around the world sharing
original data and discussing the latest evidence-based
approaches to treating hematologic disorders.
International Conference on
Malignant Lymphoma
June 18 – 22, 2019
Lugano, Switzerland
At the 15th International Conference on Malignant
Lymphoma, the scientific community involved in the
study and treatment of lymphoid neoplasms present
the latest basic and translational science in the field.
International Society on Thrombosis and
Haemostasis’ Congress and Annual Scientific
and Standardization Committee Meeting
July 6 – 10, 2019
Melbourne, Australia
The International Society on Thrombosis and
Haemostasis’ 2019 Congress, a global meeting in
thrombosis, hemostasis, and vascular biology, will be
attended by thousands of the world’s experts.
Amsterdam, The Netherlands
Immunogenicity
The development of factor VIII inhibitors with the use of ADVATE was evaluated in
clinical trials with pediatric PTPs (<6 years of age with ≥50 factor VIII exposures)
and PTPs (≥10 years of age with ≥150 factor VIII exposures). Of 276 subjects who
were treated with ADVATE for at least 10 exposure days or on study for a minimum
of 120 days, 1 adult developed a low-titer inhibitor (2 BU in the Bethesda assay)
after 26 exposure days. Eight weeks later, the inhibitor was no longer detectable,
and in vivo recovery was normal at 1 and 3 hours after infusion of another
marketed recombinant factor VIII concentrate. This event results in a factor VIII
inhibitor frequency in PTPs of 0.4% (95% CI of 0.01 and 2% for the risk of any
factor VIII inhibitor development). No factor VIII inhibitors were detected in the
53 treated pediatric PTPs. USE IN SPECIFIC POPULATIONS
In clinical trials that enrolled previously untreated subjects (defined as having had
up to 3 exposures to a factor VIII product at the time of enrollment),
16 (29.1%) of 55 subjects who received ADVATE developed inhibitors to factor VIII.
Seven subjects developed high titer (>5 BU) and nine subjects developed low-titer
inhibitors. Inhibitors were detected at a median of
13 exposure days (min-max: 6−26 exposure days) to the product. Pediatric Use
Pharmacokinetic studies in children have demonstrated higher clearance, a shorter
half-life and lower recovery of factor VIII compared to adults. This may be explained
by differences in body composition and should be taken into account when dosing or
following factor VIII levels in the pediatric population. Because clearance (based on
per kg body weight) has been demonstrated to be higher in the pediatric population,
dose adjustment or more frequent dosing based on per kg body weight may be
needed in this population. In the ADVATE routine prophylaxis clinical trial, 3 children
aged 7 to <12 and 4 adolescents aged 12 to <16 were included in the per-protocol
analysis. The reductions in annualized bleeding rate per subject per year during any
prophylaxis regimen as compared to during on-demand therapy were similar among
children, adolescents, and adults.
Immunogenicity also was evaluated by measuring the development of antibodies
to heterologous proteins. When assessed for anti-Chinese hamster ovary (CHO) cell
protein antibodies, of 229 treated subjects, 3 showed an upward trend in antibody
titer over time and 10 showed repeated but transient elevations of antibodies.
When assessed for muIgG protein antibodies, of the 229 treated subjects, 10
showed an upward trend in anti-muIgG antibody titer over time and 2 showed
repeated but transient elevations of antibodies. Four subjects who demonstrated
antibody elevations to CHO cell or muIgG proteins, reported isolated events
of urticaria, pruritus, rash, and slightly elevated eosinophil counts. All of these
subjects had numerous repeat exposures to the product without recurrence of the
events and a causal relationship between the antibody findings and these clinical
events has not been established.
Pregnancy
Pregnancy Category C. Animal reproduction studies have not been conducted with
ADVATE. It is not known whether ADVATE can cause fetal harm when administered to
a pregnant woman or whether it can affect reproductive capacity. ADVATE should be
given to a pregnant woman only if clearly needed.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are
excreted in human milk, caution should be exercised when ADVATE is administered
to a nursing woman.
Geriatric Use
Clinical trials of ADVATE did not include sufficient numbers of subjects aged 65 and
over to determine whether they respond differently compared to younger subjects.
Individualize dose selection for geriatric patients.
Chicago, IL
ASH Meeting on Hematologic
Malignancies
September 6 – 7, 2019
Chicago, IL
Top experts in hematologic malignancies discuss
the latest developments in clinical care and
provide answers to challenging patient care
questions in a small-group setting. The program
content is structured as “How I Treat” presenta-
tions, which showcase each speaker’s evidence-
based treatment approach.
2019 ASTRO Annual Meeting
September 15 – 18, 2019
Chicago, IL
The annual meeting of the American Society for
Radiation Oncology provides a forum for more
than 11,000 attendees to discuss the translation of
scientific discoveries into clinical applications and
opportunities for cure.
When assessed for the presence of anti-human von Willebrand Factor (VWF)
antibodies, of the 228 treated subjects, none displayed laboratory evidence
indicative of a positive serologic response.
The detection of antibody formation is highly dependent on the sensitivity and
specificity of the assay. Additionally, the observed incidence of antibody (including
neutralizing antibody) positivity in an assay may be influenced by several factors
including assay methodology, sample handling, timing of sample collection,
concomitant medications, and underlying disease. For these reasons, comparison
of the incidence of antibodies to ADVATE with the incidence of antibodies to other
products may be misleading.
Post-Marketing Experience
The following adverse reactions have been identified during post-approval use
of ADVATE. Because these reactions are reported voluntarily from a population
of uncertain size, it is not always possible to reliably estimate their frequency or
establish a causal relationship to drug exposure.
Table 2 represents the most frequently reported post-marketing adverse reactions
as MedDRA Preferred Terms.
Table 2
Post-Marketing Experience
Organ System [MedDRA Primary SOC]
Preferred Term
Immune system disorders Anaphylactic reaction a
Hypersensitivity a
Blood and lymphatic system disorders Factor VIII inhibition
General disorders and administration
site conditions Injection site reaction
Chills
Fatigue/Malaise
Chest discomfort/pain
Decreased therapeutic effect
These reactions have been manifested by dizziness, paresthesias, rash, flushing, face swelling, urticaria,
and/or pruritus.
a
©2018 Shire US Inc., Lexington, MA 02421. All rights reserved. 1-800-828-2088.
SHIRE and the Shire Logo are registered trademarks of Shire Pharmaceutical Holdings
Ireland Limited or its affiliates.
ADVATE is a registered trademark of Baxalta Incorporated, a wholly owned, indirect
subsidiary of Shire plc.
Patented: see www.shire.com/legal-notice/product-patents/
Shire
Lexington, MA 02421 USA
Printed in USA
Issued 11/2016
S38308 03/18
Edinburgh, Scotland
XVIII International Workshop on
Chronic Lymphocytic Leukaemia
September 20 – 23, 2019
Edinburgh, Scotland
The 2019 meeting of the International Workshop on
Chronic Lymphocytic Leukaemia will bring together
expert hematologists, clinicians, and researchers to
discuss recent developments in the understanding
of disease biology and treatments.
ASH Clinical News
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