ASH Clinical News ACN_4.10_FULL ISSUE web | Page 33

CLINICAL NEWS
(including immunomodulatory
drugs and proteasome inhibitors).
Treatment with denosumab or ZA
continued until patients experi-
enced an on-study skeletal-related
event, bone-disease progression,
or overall disease progression.
Stratification to treatment
arms was based on the following:
• intention to undergo
autologous transplantation
• anti-MM therapy
• International Staging System
stage
• previous skeletal-related
events (yes vs. no)
• geographic region
Baseline demographics and
disease characteristics were
balanced between both groups,
and 26.7 percent of patients had
poor renal function (≤60 mL/
min), the authors reported. The
median treatment duration for
denosumab was 17.3 months
(range = 8.9-28.5 months) and
for ZA was 17.6 months (range
= 9.4-28.1 months). The median
cumulative exposure to deno-
sumab and ZA were similar (15.8
months [range = 8.18-25.79
months] and 14.78 months
[range = 7.46-24.87 months]).
The study’s primary end-
point was met: Denosumab was
non-inferior to ZA in delaying
the median time to first on-study
skeletal-related event: 22.8 months
(range = 14.7 - not estimable)
Clinical study results in children and adults receiving
prophylactic treatment over a 6-month period 1,2
The efficacy, safety and PK of ADYNOVATE were evaluated in 2 multicenter, open-label clinical studies. The pediatric
study of children <12 years of age (N=66) evaluated the immunogenicity, efficacy, PK (as compared to ADVATE ®
[Antihemophilic Factor (Recombinant)]), and safety of ADYNOVATE twice-weekly prophylaxis (40-60 IU/kg) and
determined hemostatic efficacy in the treatment of bleeding episodes for 6 months. The pivotal trial of children and
adults ≥12 years (N=137) evaluated ADYNOVATE twice-weekly prophylaxis (40-50 IU/kg) vs on-demand (10-60 IU/kg)
treatment, and determined hemostatic efficacy in the treatment of bleeding episodes for 6 months. 1-3
Proven prophylaxis with ADYNOVATE
ZERO
MEDIAN ABR FOR
JOINT & SPONTANEOUS 1
In pediatric patients <12 years: Joint: 0.0 (IQR: 1.9) median ABR 3 ;
Spontaneous: 0.0 (IQR: 1.9) median ABR. 3
In adults and children ≥12 years: Joint: Prophylaxis 0.0 (IQR: 2.0) median ABR
vs on-demand 38.1 (IQR: 20.1) median ABR. 1,3 Spontaneous: Prophylaxis 0.0
(IQR: 2.2) median ABR vs on-demand 21.6 (IQR: 22.0) median ABR. 1,3
Consistent dosing1
+ In the clinical studies, the majority of children and adults did not have a dose adjustment
+ 98% of adults and children (12 years and older) did not have a dose adjustment (118 of 120)
1,2
1
— Two subjects increased their dose to 60 IU/kg due to bleeding in target joints
+ 91% of children (less than 12 years) did not have a dose adjustment (60 of 66)
2
— Reported reasons for dose adjustment included FVIII trough levels <1%, increased risk of bleeding,
and bleeding episodes
Neutralizing Antibodies
Formation of neutralizing antibodies (inhibitors)
to factor VIII can occur following administration
of ADYNOVATE. Monitor patients regularly for the
development of factor VIII inhibitors by appropriate
clinical observations and laboratory tests. Perform
an assay that measures factor VIII inhibitor
concentration if the plasma factor VIII level fails to
increase as expected, or if bleeding is not controlled
with expected dose.
ADVERSE REACTIONS
The most common adverse reactions (≥1% of
subjects) reported in the clinical studies were
headache and nausea.
Please see the following page for
the Brief Summary of the ADYNOVATE
full Prescribing Information.
For full Prescribing Information,
visit www.ADYNOVATEPRO.com.
References: 1. ADYNOVATE Prescribing Information. 2. Mullins ES, Stasyshyn O, Alvarez-Román MT, et al. Extended
half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A. Haemophilia.
2016 Nov 27. doi: 10.1111/hae.13119 [Epub ahead of print]. 3. Data on file.
©2017 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 and ADYNOVATE are trademarks or registered trademarks of Baxalta Incorporated, a wholly owned, indirect
subsidiary of Shire plc.
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