CLINICAL NEWS
TABLE 2.
Pharmacokinetic Parameters After Single Dose of Emicizumab 6 mg/kg
Value*
T max C max AUC at Day 28 T ½
6.95 days
(3.99-7.18) 31.8 µg/mL
(19.3) 662.5
(19.7) 30.2
(35.8)
*Median (range) for T max and geometric mean for all other parameters
C max = peak serum concentration; T max = time to peak serum concentration; AUC = area under the curve
similar to the clinically confirmed dosing regimen,” the
authors reported. Pharmacokinetic parameters after single
emicizumab 6 mg/kg administration were consistent with
values observed in previous studies with emicizumab (see
TABLE 2 ).
Five patients reported 14 adverse events (AEs),
including one grade 3 serious AE (worsening of hyperten-
sion). No AEs were deemed related to the study drug, and
the investigators did not detect anti-drug antibodies.
Six of seven patients had no bleeds while receiving
once-monthly emicizumab. One patient experienced three
spontaneous nose bleeds on days 12, 14, and 21, which did
not require treatment.
The analysis is limited by the small patient population
and short follow-up, Dr. Jiménez-Yuste noted, adding that
the HAVEN 4 study is now fully enrolled (n=48, including
the pharmacokinetic run-in cohort). Emicizumab also
is being studied in patients with hemophilia A without
inhibitors in the ongoing HAVEN 3 study.
The authors report financial relationships with Roche
and Genentech, the manufacturer of emicizumab.
REFERENCE
Jiménez-Yuste V, Shima M, Fukutake K, et al. Emicizumab subcutaneous dosing every 4 weeks for
the management of hemophilia A: preliminary data from the pharmacokinetic run-in cohort of a
multicenter, open-label, phase 3 study (HAVEN 4). Abstract #86. Presented at the 2017 American
Society of Hematology Annual Meeting, December 9, 2017; Atlanta, GA.
Annual meeting attendees between sessions in the Georgia World Congress Center.
Could Adding Sotatercept to Ruxolitinib Improve
MPN-Associated MF and Anemia?
The JAK1 inhibitor ruxolitinib is the only therapy approved
by the U.S. Food and Drug Administration for myelofibro-
sis (MF), but it often worsens anemia, which is common
in myeloproliferative neoplasm (MPN)-associated MF.
According to data presented at the 2017 ASH Annual
Meeting, the fusion protein sotatercept improves anemia
symptoms in patients with MPN-associated MF, both
as a single agent and when used in combination with
ruxolitinib.
“Sotatercept binds to ligands that belong to the [trans-
forming growth factor-beta] superfamily,” lead author
Prithviraj Bose, MD, of the Department of Leukemia at
the University of Texas MD Anderson Cancer Center in
Houston, explained to ASH Clinical News. “By sequestering
[these proteins], sotatercept inhibits them from binding to
the type 2 receptors and suppressing erythropoiesis.”
Dr. Bose presented updated results from a phase II trial
of sotatercept, a first-in-class, activin receptor IIA ligand
trap, in adult patients with primary, post-polycythemia
vera (PPV), or post-essential thrombocythemia (PET) MF.
Patients were included in the study if they had a hemoglo-
bin (Hgb) <10 g/dL during the 12 weeks preceding study
entry, had a Hgb <10 g/dL with sporadic red blood cell
(RBC) transfusions, or were RBC transfusion–dependent
ASHClinicalNews.org
(defined by the International Working Group for Myelo-
proliferative Neoplasms Research and Treatment 2013
criteria).
“The trial was initially conceived of as a single-arm
trial, with patients receiving sotatercept alone, but, seeing
the activity in those patients, we realized a greater unmet
need in patients on ruxolitinib, which actually worsens
anemia initially,” Dr. Bose noted. “Adding sotatercept
would be a way of counteracting that anemia and allow-
ing patients to stay on ruxolitinib and optimize the dose.”
Thirty-five people were treated at the time of data
presentation: Twenty-four patients (median age = 66.5 years;
range = 47-83 years) received sotatercept monotherapy
at subcutaneous doses of 0.75 mg/kg (n=11) or 1 mg/kg
(n=13) every three weeks, and 11 patients (median age = 67
years; range = 57-75 years) received sotatercept 0.75 mg/kg
plus ruxolitinib. Patients in the combination cohort had
received ruxolitinib at a stable dose for at least six months
within at least two months prior to study entry.
In the sotatercept monotherapy cohort, 20 patients had
primary MF, three had PET MF, and one had PPV MF,
with the following detected mutations: JAK2V617F (n=16),
MPLW515L (n=3), and CALR exon 9 indels (n=3). One
patient had none of these mutations, and in another, the
driver mutation status was unknown. In 19 patients, the
median number of prior therapies was one (range = 1-5
therapies), while five were treatment-naïve.
In the combination cohort, six patients had PMF, two
had PPV MF, and one had myelodysplastic syndromes/
MPN, with the following detected mutations: JAK2V617F
(n=7), MPLW515L (n=1), and CALR exon 9 indels (n=1).
Patients received a median of two prior therapies (range =
1-4 therapies).
The median time from diagnosis was 1.2 years (range =
0.2-5.8 years) in the monotherapy group and 1.9 years
(range = 0.4-11 years) in the combination cohort.
At the time of presentation, 28 patients were evalu-
able for response, 18 in the monotherapy group and 10
in the combination group. Dr. Bose noted that “Patients
were required to be on study for at least 12 weeks, to
exclude people who had an improvement in Hgb but not
a sustained improvement, or who went off study for some
other reason.”
Seven of the 18 evaluable patients in the monotherapy
group (39%) responded to sotatercept, including four peo-
ple who experienc