dexamethasone (DVTd) to treat adults with newly diag-
nosed MM who are eligible for autologous hematopoietic
cell transplantation.
Approval of this frontline, quadruplet regimen was
based on data from the open-label, randomized phase
III CASSIOPEIA trial, which compared induction and
consolidation treatment with either daratumumab 16 mg/
kg plus bortezomib, thalidomide, and dexamethasone
(VTd) or VTd alone. After a median follow-up of 18.8
months (range = 0-32.2), DVTd was associated with a 53%
reduction in the risk of progression or death compared
with VTd alone. DVTd also appeared to be associated with
higher rates of stringent CR at 100 days post-transplant
(28.9% vs. 20.3%).
There were no significant differences in the number
or type of serious AEs between the two arms, but AEs
that occurred ≥5% more frequently in the DVTd arm
than the VTd arm included infusion reactions, nausea,
neutropenia, thrombocytopenia, lymphopenia, and
cough.
The application for this combination was granted pri-
ority review. Daratumumab also is approved, in combina-
tion or as monotherapy, for the treatment of patients with
newly diagnosed, transplant-ineligible MM and those
with previously treated MM.
Biosimilar: Pegfilgrastim-bmez
On November 5, 2019, the FDA approved pegfilgrastim-
bmez, a leukocyte growth factor biosimilar to pegfil-
grastim (Neulasta), to decrease the incidence of febrile
neutropenia in patients with non-myeloid malignancies
who are receiving myelosuppressive chemotherapy.
The biosimilar’s approval was based on data demon-
strating that no clinically meaningful differences between
pegfilgrastim-bmez and its reference product, including
findings from a pharmacokinetics and pharmacodynamics
study comparing U.S.-sourced and E.U.-sourced reference
pegfilgrastim.
The FDA noted that pegfilgrastim-bmez is not indi-
cated for the mobilization of peripheral blood progenitor
cells for hematopoietic cell transplantation.
Zanubrutinib
On November 14, 2019, the FDA granted accelerated
approval to zanubrutinib, an inhibitor of Bruton ty-
rosine kinase (BTK), to treat adults with mantle cell
lymphoma (MCL) who have received ≥1 prior therapy.
Zanubrutinib is the third BTK inhibitor to be approved
by the FDA for treatment of MCL, after ibrutinib in
2013 and acalabrutinib in 2017.
The zanubrutinib approval was based on results from
a single-arm clinical trial with a primary endpoint of ORR
(defined as complete or partial shrinkage of tumors after
treatment) in 86 patients. Eighty-four percent of patients
had a response, and the median duration of response was
19.5 months (range not provided). An additional single-
arm trial, in which 84% of 32 patients had a response with
a median duration of response of 18.5 months (range not
provided), supported these findings.
Notably, these trials were conducted outside the U.S.,
and this approval is the first based on efficacy data pre-
dominantly collected from Chinese research, according to
zanubrutinib’s manufacturer, BeiGene.
AEs associated with zanubrutinib include neutro-
penia, thrombocytopenia, leukopenia, anemia, upper
respiratory tract infection, bruising, rash, diarrhea, and
cough. The FDA’s approval notes that patients should be
monitored for bleeding, infection, cardiac arrhythmias,
and cytopenias.
In addition to accelerated approval, zanubrutinib was
granted priority review and orphan product and break-
through therapy designations.
Acalabrutinib
On November 21, 2019, the FDA granted a supplemental
approval to acalabrutinib for the treatment of adults
with CLL or small lymphocytic lymphoma (SLL). Acal-
abrutinib was previously approved by the FDA for the
treatment of MCL.
This new indication for CLL/SLL was based on results
from two randomized clinical trials that compared acal-
abrutinib with other standard treatments: ELEVATE-TN,
which enrolled 535 patients with treatment-naïve CLL,
and ASCEND, which enrolled 310 patients with pre-
viously treated CLL. In both trials, participants who
received acalabrutinib had longer progression-free sur-
vival, compared with the standard treatment arms.
The most common AEs related to acalabrutinib were
anemia, neutropenia, upper respiratory tract infection,
thrombocytopenia, headache, diarrhea, and musculoskel-
etal pain. The approval letter also noted that patients
should be monitored for symptoms of arrhythmia, based
on the risk of atrial fibrillation and atrial flutter observed
in clinical trials.
This approval decision was made as part of Project
Orbis, a collaboration with the Australian Therapeutic
Goods Administration and Health Canada that provides
a framework for concurrent submission and review of
oncology drug applications among the FDA’s interna-
tional partners. Both partner countries approved acal-
abrutinib for the CLL/SLL indication.
This review also used the FDA’s Real-Time Oncology
Review program, through which the agency can access
clinical trial data before the information is formally
submitted. ●
March 2020
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