Genmab
A/S announced that the U.S. Food and Drug Administration (FDA) has
approved DARZALEX (daratumumab) injection for intravenous infusion for the
treatment of patients with multiple myeloma who have received at least three
prior lines of therapy, including a proteasome inhibitor (PI) and an
immunomodulatory agent (IMiD), or who are double-refractory to a PI and IMiD. This indication is approved under
accelerated approval based on response rate. Continued approval for this
indication may be contingent upon verification and description of clinical
benefit in confirmatory trials.
DARZALEX
is the first human CD38 monoclonal antibody (mAb) approved anywhere in the
world and the first therapeutic antibody ever approved to treat multiple
myeloma. The approval comes just two months after the Biologics License
Application (BLA) was accepted for Priority Review by the FDA in September
2015. In May 2013, DARZALEX received Breakthrough Therapy Designation from the
FDA for the indication approved today. In August 2012, Genmab granted Janssen
Biotech, Inc. an exclusive worldwide license to develop, manufacture and
commercialize DARZALEX.
Genmab
will receive a milestone payment from Janssen of USD 45 million associated with
the first commercial sale of the product in the United States. As this is
expected to occur quickly after this approval, Genmab is improving its
financial guidance for the year. See the Outlook section of this.
The
pivotal Phase II MMY2002 (SIRIUS) study showed treatment with single-agent
DARZALEX resulted in an overall response rate (ORR) of 29.2 percent in patients
who received a median of five prior lines of therapy, including a PI and an
IMiD, and is expected to be published in a top medical journal soon. Stringent
complete response (sCR) was reported in 2.8 percent of patients, very good
partial response (VGPR) was reported in 9.4 percent of patients, and partial
response (PR) was reported in 17 percent of patients. For responders, the
median duration of response was 7.4 months. At baseline, 97 percent of patients
were refractory to their last line of therapy, 95 percent were refractory to
both a PI and an IMiD, and 77 percent were refractory to alkylating agents.
Sixty-three percent were refractory to pomalidomide, and 50 percent were
refractory to carfilzomib.
The
warnings and precautions for DARZALEX include infusion-related reactions (IRRs)
and interference with serological testing.The most commonly
occurring adverse reactions (in 20 percent or more of patients in three pooled
clinical studies) were IRRs, fatigue, nausea, back pain, anemia, neutropenia
(abnormally low levels of neutrophils, a type of white blood cell) and
thrombocytopenia (abnormally low levels of platelets in the blood).
In data
from three pooled clinical studies including a total of 156 patients, four
percent of patients discontinued treatment due to adverse reactions, none of
which were considered drug-related. IRRs were reported in approximately half of
all patients treated with DARZALEX, the majority of which (91 percent) occurred
during the first infusion. Seven percent of patients had an IRR at more than
one infusion. Common (>=5 percent) symptoms of IRRs included nasal
congestion, chills, cough, allergic rhinitis, throat irritation, dyspnea, and
nausea, and these were mild to moderate in severity. Severe
IRRs (4 percent), including bronchospasm (1.3 percent), hypertension (1.3
percent), and hypoxia, or decreased oxygen supply to the tissues (0.6 percent),
were also reported.
The recommended dose of DARZALEX is 16 mg/kg body
weight administered as an intravenous infusion. The dosing
schedule begins with weekly administration (weeks 1 to 8), and reduces in
frequency to every two weeks (weeks 9-24) and ultimately every four weeks (week
25 onwards until disease progression).
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