RELIEF™ trial demonstrated statistically
significant reductions in oral ulcers with apremilast 30 mg versus
placebo through week 12
Significant improvements in key secondary
endpoints, including oral ulcer pain, overall disease activity and
quality of life
Data presented at the 2018 AAD Annual
Meeting
Regulatory submissions in the U.S. and Japan
planned for later this year
Celgene Corporation (NASDAQ:CELG) today announced that data from
the phase III RELIEF™ clinical trial of OTEZLA® (apremilast) in
patients with active Behçet’s Disease with oral ulcers were
presented in a late-breaking oral presentation at the 2018 American
Academy of Dermatology (AAD) Annual Meeting. The results showed
statistically significant reductions in oral ulcers with apremilast
30 mg twice daily (BID) versus placebo through week 12. OTEZLA
(apremilast) is Celgene’s oral selective inhibitor of
phosphodiesterase 4 (PDE4).
Behçet’s Disease is a rare, chronic, multi-system inflammatory
syndrome. Oral ulcers, the most common manifestation of Behçet’s
Disease, can be disabling and have a substantial effect on quality
of life. This study primarily evaluated the effect of apremilast on
recurring oral ulcers in patients with active Behçet’s Disease who
were previously treated with at least one topical or systemic
medication.
“Reducing oral ulcers, which are painful and can negatively
impact quality of life, is an important goal in the treatment of
people with Behçet’s syndrome,” said Gulen Hatemi, M.D., Associate
Professor, Istanbul University Cerrahpassa Medical School. “These
findings suggest that apremilast, which reduced oral ulcers and
oral ulcer pain, and improved disease activity in this pivotal
study, has the potential to be a treatment option for patients with
active Behçet’s syndrome with oral ulcers, for which few treatment
alternatives exist.”
In the study, a total of 207 patients were randomized to
apremilast 30 mg BID or placebo. At week 12, the area under the
curve (AUC) for the number of oral ulcers was statistically
significantly reduced with apremilast 30 mg BID versus placebo
(129.5 vs. 222.1; P<0.0001), the trial’s primary endpoint. The
AUC assesses the change in the number of oral ulcers over time,
accounting for the clinical characteristic that oral ulcers
repeatedly remit and recur. Statistically significant improvements
were also seen with apremilast in multiple secondary endpoints,
including oral ulcer pain (P<0.0001), overall disease activity
(Behçet’s Syndrome Activity Score: P<0.0001; Behçet’s Disease
Current Activity Index: P=0.0335) and quality of life
(P=0.0003).
The most common adverse events (AEs) observed in the trial were
diarrhea (41.3 percent with apremilast, 19.4 percent for placebo),
nausea (19.2 percent with apremilast, 10.7 percent for placebo),
headache (14.4 percent for apremilast, 9.7 percent for placebo) and
upper respiratory tract infection (11.5 percent for apremilast, 4.9
percent for placebo). The safety profile was consistent with the
known safety profile of apremilast.
Celgene plans to submit supplemental New Drug Applications for
apremilast 30 mg BID for the treatment of active Behçet’s Disease
with oral ulcers in the U.S. and Japan in the second half of this
year. The Company also plans to submit a Type II Variation to the
Marketing Authorization Application in the EU in 2019.
“The positive phase III findings in Behçet’s Disease reflect the
unique aspects of the profile of OTEZLA® (apremilast) 30 mg across
inflammatory-related diseases,” said Terrie Curran, President,
Celgene Inflammation and Immunology. “OTEZLA® (apremilast) 30 mg
has the potential to provide a clinically meaningful new treatment
option for patients and doctors and to become the first product
indicated specifically for the treatment of active Behçet’s Disease
with oral ulcers.”
Apremilast is not approved for the treatment of Behçet’s Disease
in any country.
About the RELIEF™ Study
The RELIEF™ study is a phase III randomized, placebo-controlled,
double-blind study evaluating apremilast 30 mg BID in 207 patients
with active Behçet’s Disease who were previously treated with at
least one topical or systemic medication. This 52-week study was
conducted at 63 sites across 10 countries. The primary endpoint was
the area under the curve (AUC) for the number of oral ulcers at
week 12. Secondary objectives of the study included change from
baseline in pain of oral ulcers, Behçet’s Syndrome Activity Score,
Behçet’s Disease Current Activity Index and Behçet’s Disease
quality of life score at week 12.
About Behçet’s Disease
Although the root cause is unknown, Behçet’s Disease is
associated with abnormalities of the immune system and inflammation
of the blood vessels. Behçet’s Disease is characterized by
recurrent oral and genital ulcers, skin lesions, uveitis,
arthritis, vasculopathy, and central nervous system and
gastrointestinal involvement.
Prevalence of Behçet’s Disease is highest in the Middle East,
Asia and Japan. Behçet’s Disease has been classified in the U.S. as
a rare or “orphan” disease by the National Institutes of Health. At
this time, there are no approved therapies to treat Behçet’s
Disease in the U.S.
About OTEZLA®
OTEZLA® (apremilast) 30 mg tablets is an oral small-molecule
inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic
adenosine monophosphate (cAMP). PDE4 inhibition results in
increased intracellular cAMP levels, which is thought to indirectly
modulate the production of inflammatory mediators. The specific
mechanism(s) by which OTEZLA exerts its therapeutic action in
patients is not well defined.
U.S. PRESCRIBING INFORMATION
INDICATIONS
OTEZLA® (apremilast) is indicated for the treatment of patients
with moderate to severe plaque psoriasis who are candidates for
phototherapy or systemic therapy.
OTEZLA is indicated for the treatment of adult patients with
active psoriatic arthritis.
IMPORTANT SAFETY INFORMATION
Contraindications
OTEZLA® (apremilast) is contraindicated in patients with a known
hypersensitivity to apremilast or to any of the excipients in the
formulation
Warnings and Precautions
Diarrhea, Nausea and Vomiting: Cases of severe diarrhea, nausea,
and vomiting were associated with the use of OTEZLA. Most events
occurred within the first few weeks of treatment. In some cases,
patients were hospitalized. Patients 65 years of age or older and
patients taking medications that can lead to volume depletion or
hypotension may be at a higher risk of complications from severe
diarrhea, nausea, or vomiting. Monitor patients who are more
susceptible to complications of diarrhea or vomiting; advise
patients to contact their healthcare provider. Consider OTEZLA dose
reduction or suspension if patients develop severe diarrhea,
nausea, or vomiting
Depression: Carefully weigh the risks and benefits of treatment
with OTEZLA for patients with a history of depression and/or
suicidal thoughts/behavior, or in patients who develop such
symptoms while on OTEZLA. Patients, caregivers, and families should
be advised of the need to be alert for the emergence or worsening
of depression, suicidal thoughts or other mood changes, and they
should contact their healthcare provider if such changes occur
Psoriasis: Treatment with OTEZLA is
associated with an increase in depression. During clinical trials,
1.3% (12/920) of patients reported depression compared to 0.4%
(2/506) on placebo; Depression was reported as serious in 0.1%
(1/1308) of patients exposed to OTEZLA, compared to none in
placebo-treated patients (0/506). Suicidal behavior was observed in
0.1% (1/1308) of patients on OTEZLA, compared to 0.2% (1/506) on
placebo. One patient treated with OTEZLA attempted suicide; one
patient on placebo committed suicide
Psoriatic Arthritis: Treatment with
OTEZLA is associated with an increase in depression. During
clinical trials, 1.0% (10/998) reported depression or depressed
mood compared to 0.8% (4/495) treated with placebo. Suicidal
ideation and behavior was observed in 0.2% (3/1441) of patients on
OTEZLA, compared to none in placebo treated patients. Depression
was reported as serious in 0.2% (3/1441) of patients exposed to
OTEZLA, compared to none in placebo treated patients (0/495). Two
patients who received placebo committed suicide compared to none on
OTEZLA
Weight Decrease: Monitor body weight regularly; evaluate
unexplained or clinically significant weight loss, and consider
discontinuation of OTEZLA
Psoriasis: Body weight loss of
5-10% occurred in 12% (96/784) of patients treated with OTEZLA and
in 5% (19/382) of patients treated with placebo. Body weight loss
of ≥10% occurred in 2% (16/784) of patients treated with OTEZLA
compared to 1% (3/382) of patients treated with placebo
Psoriatic Arthritis: Body weight
loss of 5-10% was reported in 10% of patients taking OTEZLA and in
3.3% of patients taking placebo.
Drug Interactions: Apremilast exposure was decreased when OTEZLA
was co-administered with rifampin, a strong CYP450 enzyme inducer;
loss of OTEZLA efficacy may occur. Concomitant use of OTEZLA with
CYP450 enzyme inducers (e.g., rifampin, phenobarbital,
carbamazepine, phenytoin) is not recommended
Adverse Reactions
Psoriasis: Adverse reactions
reported in ≥5% of patients were (OTEZLA%, placebo%): diarrhea (17,
6), nausea (17, 7), upper respiratory tract infection (9, 6),
tension headache (8, 4), and headache (6, 4)
Psoriatic Arthritis: Adverse
reactions reported in at least 2% of patients taking OTEZLA, that
occurred at a frequency at least 1% higher than that observed in
patients taking placebo, for up to 16 weeks (after the initial
5-day titration), were (OTEZLA%, placebo%): diarrhea (7.7, 1.6);
nausea (8.9, 3.1); headache (5.9, 2.2); upper respiratory tract
infection (3.9, 1.8); vomiting (3.2, 0.4); nasopharyngitis (2.6,
1.6); upper abdominal pain (2.0, 0.2)
Use in Specific
Populations
Pregnancy and Nursing Mothers: OTEZLA is Pregnancy Category C;
it has not been studied in pregnant women. Use during pregnancy
only if the potential benefit justifies the potential risk to the
fetus. It is not known whether apremilast or its metabolites are
present in human milk. Caution should be exercised when OTEZLA is
administered to a nursing woman
Renal Impairment: OTEZLA dosage should be reduced in patients
with severe renal impairment (creatinine clearance less than 30
mL/min); for details, see Dosage and Administration, Section 2, in
the Full Prescribing Information
Please click here for Full Prescribing
Information.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global pharmaceutical company engaged primarily in the
discovery, development and commercialization of innovative
therapies for the treatment of cancer and inflammatory diseases
through next‐generation solutions in protein homeostasis,
immuno‐oncology, epigenetics, immunology and neuro‐inflammation.
For more information, please visit www.celgene.com. Follow
Celgene on Social Media: @Celgene, Pinterest, LinkedIn,
Facebook and YouTube.
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are generally statements that are not historical facts.
Forward-looking statements can be identified by the words
“expects,” “anticipates,” “believes,” “intends,” “estimates,”
“plans,” “will,” “outlook” and similar expressions. Forward-looking
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assumptions and projections, and speak only as of the date they are
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otherwise required by law. Forward-looking statements involve
inherent risks and uncertainties, most of which are difficult to
predict and are generally beyond our control. Actual results or
outcomes may differ materially from those implied by the
forward-looking statements as a result of the impact of a number of
factors, many of which are discussed in more detail in our Annual
Report on Form 10-K and our other reports filed with the U.S.
Securities and Exchange Commission.
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Celgene CorporationInvestors:Patrick E. Flanigan III,
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