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Amgen
AMGN and AstraZeneca
AZN today announced that
AMAGINE-3(TM) , a pivotal, multi-arm Phase 3 trial evaluating two doses of
brodalumab in more than 1,800 patients with moderate-to-severe plaque
psoriasis, met its primary endpoints when compared with both Stelara(R)
(ustekinumab) and placebo at week 12. Brodalumab was shown to be superior to
Stelara on the primary endpoint of achieving total clearance of skin
disease, as measured by the Psoriasis Area Severity Index (PASI 100). When
compared with placebo, a significantly greater proportion of patients
treated with brodalumab achieved at least a 75 percent improvement from
baseline in disease severity at week 12, as measured by the Psoriasis Area
Severity Index (PASI 75). A significantly greater proportion of patients
treated with brodalumab also achieved clear or almost clear skin at week 12
compared with placebo, according to the static Physician Global Assessment
(sPGA 0 or 1). All key secondary endpoints comparing brodalumab with Stelara
and placebo were also met.
Results showed that 36.7 percent of patients in the brodalumab 210 mg group,
27.0 percent of patients in the brodalumab 140 mg group, 18.5 percent of
patients in the Stelara group and 0.3 percent of patients in the placebo
group achieved total clearance of skin disease (PASI 100). In addition,
85.1 percent of patients in the brodalumab 210 mg group, 69.2 percent of
patients in the brodalumab 140 mg group, 69.3 percent of patients in the
Stelara group and 6.0 percent of patients in the placebo group achieved PASI
75.
"Despite a variety of treatment options available for psoriasis, many
patients still do not meet skin clearance goals," said Sean E. Harper, M.D.,
executive vice president of Research and Development at Amgen. "These
results are of particular importance as they are the first to demonstrate
superiority to Stelara in achieving total skin clearance, and the second
positive pivotal Phase 3 study evaluating brodalumab in patients with
moderate-to-severe plaque psoriasis."
The most common adverse events that occurred in the brodalumab arms (more
than 5 percent of patients in either group) were common cold, joint pain,
upper respiratory tract infection and headache. Serious adverse events
occurred in 1.4 percent of patients in the 210 mg group and 1.6 percent of
patients in the 140 mg group compared with 0.6 percent for Stelara and 1.0
percent for placebo during the placebo-controlled period.
Brodalumab is the only investigational treatment in development that binds
to the interleukin-17 (IL-17) receptor and inhibits inflammatory signaling
by blocking the binding of several IL-17 cytokines (A, F, A/F and C) to the
receptor. The IL-17 receptor and cytokine family play a central role in
development and clinical manifestation of plaque psoriasis.
"These results add to the growing body of evidence supporting the potential
value that brodalumab may bring to the treatment of psoriasis by targeting
the IL-17 receptor," said Briggs W. Morrison, M.D., executive vice president
of Global Medicines Development at AstraZeneca. "We look forward to sharing
results later this year from AMAGINE-2(TM) , our remaining head-to-head
study evaluating brodalumab versus Stelara."
The AMAGINE program is composed of three Phase 3 studies designed to assess
the efficacy and safety of brodalumab in patients with moderate-to-severe
plaque psoriasis. Top-line results from AMAGINE-1(TM) , designed to assess
the efficacy and safety of brodalumab compared with placebo, were released
in May 2014. Detailed results from the AMAGINE-3 study will be submitted to
the appropriate scientific forum for presentation and/or publication.
Results from AMAGINE-2 are expected by year end.
AMAGINE-3 Study Design
AMAGINE-3 is a Phase 3 study that assessed the safety and efficacy of
brodalumab given at two doses every two weeks via subcutaneous injection
compared with placebo and Stelara in patients with moderate-to-severe plaque
psoriasis. The study also assessed the safety and efficacy of four
maintenance regimens of brodalumab. The primary endpoint comparing
brodalumab with Stelara was the proportion of patients achieving total
clearance of skin disease, as measured by PASI 100 at week 12. When
comparing brodalumab with placebo, the primary endpoints included the
proportion of patients achieving at least a 75 percent improvement from
baseline in disease severity (PASI 75) at week 12, and the achievement of
clear or almost clear skin, according to the sPGA (0 or 1) at week 12.
The study began with a 12-week, double-blind, active comparator- and
placebo-controlled induction phase, where patients were randomized in a
2:2:1:1 ratio to receive brodalumab (210 mg or 140 mg), Stelara (per the
labeled dose), or placebo. At week 12, patients originally randomized to
either brodalumab arm were re-randomized 2:2:2:1 into the maintenance phase
to receive brodalumab 210 mg or 140 mg at four different maintenance
regimens. Patients originally randomized to Stelara continued to receive the
same treatment, and those originally randomized to receive placebo began 210
mg of brodalumab every two weeks.
At week 52, patients entered the long-term extension portion of the study,
and those who were originally randomized to receive Stelara began receiving
210 mg of brodalumab every two weeks. All other patients continued on
treatment with brodalumab at the same dose they were being treated with at
week 52. Patients may be enrolled in the study for up to 271 weeks
(approximately five years).
A PASI score is a measure of psoriatic plaque redness, scaling and thickness
and the extent of involvement in each region of the body. Treatment efficacy
is often measured by the reduction of PASI from baseline (e.g., a 75 percent
reduction is known as PASI 75, a 90 percent reduction is known as PASI 90
and PASI 100 is total clearance of skin disease).
sPGA is a physician's rating of psoriasis severity at a given point in time
based on plaque, scaling and redness. A physician can rate a patient's
psoriasis as clear (0), almost clear (1), mild (2), moderate (3), severe
(4), or very severe (5).
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