On Location
Pacritinib Leads to Better Symptom Control,
Improved Cytopenias in Myelofibrosis
have been able to simultaneously improve splenomegaly
symptoms from which patients suffer while also impacting,
in a favorable way, their cytopenias.”
In PERSIST-1, Dr. Mesa and colleagues enrolled 327
patients (median time from diagnosis, 1.12 years) with primary myelofibrosis, post-polycythemia vera myelofibrosis,
“Patients with myelofibrosis can have difficult sympCompared with other available treatments, the JAK2
or post-essential thrombocythemia myelofibrosis. Thirtytoms that can have a signifi cant negative impact on their
inhibitor pacritinib leads to more effective spleen volume
two percent of patients had platelet counts <100,000 /µL,
reduction and better symptom control in patients with my- quality of life,” Ruben A. Mesa, MD, professor of medicine
and 15 percent had platelet counts <50,000/µL.
at the Mayo Clinic in Scottsdale, Arizona, and the first
elofibrosis, according to results of the phase III PERSIST-1
Patients were randomly assigned 2:1 to receive either
author of the study said during a press conference. “In our
study presented at the 2015 American Society of Clinical
daily oral pacritinib (n=220) or best available treatment
therapies for myelofibrosis, we have not had agents that
Oncology meeting.
(n=107), which included erythropoietin-stimulating agents,
immunomodulatory drugs,
and hydroxyurea, though use
of ruxolitinib was not allowed.
“One of the limitations
of the only currently FDAapproved therapy, ruxolitinib,
is that it is indicated in patients
with a platelet count above
50,000/µL,” Dr. Mesa explained
ADVERSE REACTIONS
Lyophilized Powder for Solution for Intravenous Injection
in an interview with ASH CliniCommon adverse reactions observed in greater than 5% of
Brief Summary of Prescribing Information: Please see
cal News.
subjects in the clinical trial were development of inhibitors to
package insert for full Prescribing Information.
“Many patients with very
porcine factor VIII.
advanced disease have signifiINDICATIONS AND USAGE
Clinical Trials Experience
cant thrombocytopenia, and
OBIZUR, Antihemophilic Factor (Recombinant), Porcine
Because clinical trials are conducted under widely varying
that is a limiter for ruxolitinib
Sequence, is a recombinant DNA derived, antihemophilic
conditions, adverse reaction (AR) rates observed in the clinical
because the drug can cause
factor indicated for the treatment of bleeding episodes in
trials of a drug cannot be directly compared to rates in the
thrombocytopenia.”
adults with acquired hemophilia A.
clinical trials of another drug and may not reflect the rates
The primary endpoint was
observed in clinical practice.
Limitations of Use:
defined
as spleen volume reThe safety and efficacy of OBIZUR was evaluated in a multi• Safety and efficacy of OBIZUR has not been established in
duction (SVR) of ≥35 percent
center, prospective, open-label, clinical trial that investigated
patients with baseline anti-porcine factor VIII inhibitor titer
at 24 weeks in the intent-toadult patients with acquired hemophilia A. Twenty-nine adult
greater than 20 BU.
subjects were enrolled in the study, received at least one dose
treat population. The median
of OBIZUR and were evaluable for safety. Of the 29 adult
• OBIZUR is not indicated for the treatment of congenital
duration of treatment was 16.2
subjects, 10 were between the ages of 40 and 65, and 19 were
hemophilia A or von Willebrand disease.
months in the pacritinib arm,
65 years of age or older (18 Caucasian, 6 African-American,
CONTRAINDICATIONS
versus 5.9 months in the best
and 5 Asian). Ten (34%) subjects were female.
available therapy (BAT) arm.
OBIZUR is contraindicated in patients who have had lifeThe most frequently reported adverse reaction in patients
At 24 weeks, the investigathreatening hypersensitivity reactions to OBIZUR or its
with acquired hemophilia A was the development of inhibitors
tors observed a greater SVR recomponents (including traces of hamster proteins).
to porcine factor VIII.
duction in the pacritinib group:
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions can occur with OBIZUR. OBIZUR
contains trace amounts of hamster proteins. Early signs of
allergic reactions, which can progress to anaphylaxis, include
angioedema, chest-tightness, dyspnea, hypotension,
wheezing, urticaria, and pruritus. Immediately discontinue
administration and initiate appropriate treatment if allergic
or anaphylactic-type reactions occur.
Inhibitory Antibodies
Inhibitory antibodies to OBIZUR have occurred. Monitor
patients for the development of antibodies to OBIZUR by
appropriate assays. If the plasma factor VIII level fails to
increase as expected, or if bleeding is not controlled after
OBIZUR administration, suspect the presence of an antiporcine factor VIII antibody. If such inhibitory antibodies
to anti-porcine factor VIII are suspected and there is a
lack of clinical response, consider other therapeutic options.
Monitoring Laboratory Tests
• Perform one-stage clotting assay to confirm that adequate
factor VIII levels have been achieved and maintained.
– Monitor factor VIII activity 30 minutes and 3 hours after
initial dose.
– Monitor factor VIII activity 30 minutes after
subsequent doses.
• Monitor the development of inhibitory antibodies to
OBIZUR. Perform a Nijmegen Bethesda inhibitor assay if
expected plasma factor VIII activity levels are not attained
or if bleeding is not controlled with the expected dose of
OBIZUR. Use Bethesda Units (BU) to report inhibitor levels.
Immunogenicity
All subjects were monitored for development of inhibitory
antibodies to OBIZUR using the Nijmegen modification of the
Bethesda inhibitor assay. A subject was considered to have
developed an OBIZUR inhibitor if the titer was ≥0.6 Bethesda
Units (BU)/mL.
Of the 29 subjects treated with OBIZUR, 19 subjects were
negative for anti-porcine factor VIII antibodies at baseline.
Five of the 19 (26%) developed anti-porcine factor VIII
antibodies following exposure to OBIZUR. Of the 10 subjects
with detectable anti-porcine factor VIII antibodies at baseline,
2 (20%) experienced an increase in titer and eight (80%)
experienced a decreasing to a non-detectable titer.
All subjects were also monitored for development of binding
antibodies to baby hamster kidney (BHK) protein by a
validated sequential ELISA (enzyme-linked immunosorbent
assay). No patients developed de novo anti-BHK antibodies.
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) posit ivity 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 OBIZUR with the incidence of
antibodies to other products may be misleading.
Baxalta and Obizur are trademarks of Baxalta Incorporated.
Manufactured by:
Baxalta US Inc.
Westlake Village, CA 91362 USA
U.S. License No. 140
• 19.1% vs. 4.7% for BAT
(p=0.0003) in the intent-totreat population
• 25% vs. 5.9% (p=0.0001) in
the evaluable population
Symptom control (a secondary endpoint defined as a 50%
or greater reduction of total
symptom score at 24 weeks)
was also improved with pacritinib:
• 24.5% vs. 6.5% for BAT
(p<0.0001) in the intent-totreat population
• 40.9% vs. 9.9% in evaluable
patients (p<0.0001)
At the time of data cut-off,
79 percent of BAT patients
crossed over to pacritinib,
while 21 percent had achieved
a >35 percent SVR.
“The distinguishing
characteristic of this study is
USBS/MG114/15-0031
August 2015