Latest & Greatest
Dabigatran Reversal
Agent Idarucizumab
Granted Priority
Review by the FDA
The U.S. Food and Drug Administration
has granted priority review to the biologics license application (BLA) for idarucizumab, which is being investigated to
specifically reverse the anticoagulant effect of dabigatran in patients
needing emergency intervention
or experiencing an uncontrolled or
life-threatening bleeding event. The
idarucizumab BLA will be reviewed
under Accelerated Approval and
is the first review for a reversal
agent for a novel oral anticoagulant
(NOAC). Currently, no NOAC has
an approved reversal agent. The
FDA granted Breakthrough Therapy
Designation for idarucizumab
in June 2014. The BLA includes
phase I data demonstrating idarucizumab’s potential to provide immediate reversal of the anticoagulant
effect of dabigatran. In these studies,
there were no clinically relevant adverse events or procoagulant effect
observed after the administration
of idarucizumab. Interim data from
the ongoing RE-VERSE AD trial,
a phase III global study investigating idarucizumab in actual clinical
settings, were also included in the
application.
Source: Boehringer Ingelheim press release
FDA Grants Priority
Review to Brentuximab Vedotin
Consolidation in
Hodgkin Lymphoma
The FDA has accepted a supplemental BLA for brentuximab
vedotin for post-transplant consolidation treatment of Hodgkin
lymphoma patients at high risk
for relapse or progression. The
FDA granted Priority Review for
the application, and the Prescription Drug User Fee Act (PDUFA)
target action date is August 18,
2015. The BLA submission is based
on positive results from the phase
III AETHERA clinical trial, which
determined whether 16 cycles of
brentuximab vedotin as consolidation therapy immediately following
an autologous stem cell transplantation (ASCT) could extend
progression-free survival (PFS) in
these high-risk Hodgkin lymphoma
patients. The positive results from
22
ASH Clinical News
the phase III AETHERA trial were published in The Lancet in March 2015 and
were presented at the 56th American
Society of Hematology Annual Meeting
in December 2014. In 329 patients with
Hodgkin lymphoma at high risk for
relapse following ASCT, brentuximab
vedotin led to a significant increase in
PFS – 43 months versus 24 months for
patients who received placebo (hazard
ratio = 0.57; p=0.001).
Source: Seattle Genetics press release
Scientists Trace
Genomic Evolution
of ALL
By using genomic sequencing of leukemia
cells from relapsed patients with acute
lymphocytic leukemia (ALL), researchers discovered key details about how ALL
cells mutate to survive chemotherapy.
These findings, published in Nature Com-
munications, will potentially lead to new
tests to monitor children in remission and
to detect signs of relapse. ALL is a leading
cause of cancer deaths in children, with
15 percent of ALL patients relapsing with
poor survival. In the study, researchers
analyzed the genomes of cells from 20
children who had ALL that returned following treatment. Cell samples were taken
at three stages – diagnosis, remission, and
relapse – to better determine the mutations that drove the relapse of leukemia.
N O W AVA I L A B L E
F O R T H E T R E A T M E N T O F P h - N E G A T I V E R E L A P S E D / R E F R A C T O RY
B - C E L L A C U T E LY M P H O B L A S T I C L E U K E M I A ( A L L )
Discover the first and only FDA-approved Bispecific CD19-directed CD3 T-cell Engager
In a phase 2, open-label, multicenter,
single-arm clinical trial:
• The primary endpoint was the complete
remission/complete remission with partial
hematological recovery (CR/CRh*) rate
within 2 cycles of treatment with BLINCYTO™.
• Eligible patients were ≥ 18 years of age with
Philadelphia chromosome-negative relapsed
or refractory B-precursor ALL.
• Relapsed or refractory was defined as relapsed
with first remission duration of ≤ 12 months
in first salvage or relapsed or refractory after
first salvage therapy or relapsed within
12 months of allogeneic hematopoietic stem
cell transplantation (HSCT), and had ≥ 10%
blasts in bone marrow.
75.3%
41.6%
(95% CI: 34.4-49.1)
of R/R ALL evaluable
patients achieved a
CR/CRh* (n=77/185)1
(95% CI: 64.2-84.4)
with CR/CRh* also had an
MRD response (defined
as MRD by PCR < 1 x 10-4)
(n=58/77)1
39%
of patients who achieved
CR/CRh* went on to receive
allogeneic transplant
(n=30/77)1
INDICATION
BLINCYTO™ is indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor
acute lymphoblastic leukemia (ALL).
This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon
verification of clinical benefit in subsequent trials.
IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES
• Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving
BLINCYTO™. Interrupt or discontinue BLINCYTO™ as recommended.
• Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO™.
Interrupt or discontinue BLINCYTO™ as recommended.
Contraindications
BLINCYTO™ is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the
product formulation.
Warnings and Precautions
• Cytokine Release Syndrome (CRS): Life-threatening or fatal CRS occurred in patients receiving BLINCYTO™. Infusion
reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients
for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine
aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated
intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage
activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO™ as outlined in the Prescribing Information (PI).