THOUSAND OAKS, Calif.,
Feb. 22, 2021 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced the submission of a supplemental New
Drug Application (sNDA) to the U.S. Food and Drug Administration
(FDA) for Otezla® (apremilast) for the treatment of
adults with mild-to-moderate plaque psoriasis who are candidates
for phototherapy or systemic therapy. The sNDA is based on data
from the Phase 3 ADVANCE trial that demonstrated oral Otezla 30 mg
twice daily achieved a statistically significant improvement in the
primary endpoint of the static Physician's Global Assessment (sPGA)
response at week 16 compared to placebo.
"Despite treatment advances, there remains an unmet need for
people with clinically mild-to-moderate plaque psoriasis who use
existing topical therapies and still have challenges managing their
disease, particularly those with disease in hard-to-treat
locations. Results from the ADVANCE trial demonstrated the
potential of Otezla to provide an oral, non-biologic option for
these patients," said David M.
Reese, M.D., executive vice president of Research and
Development at Amgen. "We look forward to working with the FDA to
potentially expand access to Otezla and deliver on our commitment
to improve outcomes for people living with mild-to-moderate plaque
psoriasis."
Otezla also demonstrated statistically significant improvements
in key secondary endpoints compared to placebo, including achieving
at least a 75% improvement from baseline in the percent of affected
body surface area (BSA), change in BSA total score from baseline
and change in Psoriasis Area and Severity Index (PASI) total score
from baseline at week 16. Adverse events observed in the ADVANCE
trial were consistent with the known safety profile of Otezla. The
most commonly reported adverse events that occurred in at least 5%
of patients in either treatment group were diarrhea, headache,
nausea, nasopharyngitis and upper respiratory tract infection.
Detailed results will be submitted for presentation at an
upcoming medical meeting.
In the U.S., Otezla is approved for the treatment of adult
patients with moderate-to-severe plaque psoriasis who are
candidates for phototherapy or systemic therapy, adult patients
with active psoriatic arthritis and for adult patients with oral
ulcers associated with Behçet's Disease. Since its initial FDA
approval in 2014, Otezla has been prescribed to more than 250,000
patients with moderate-to-severe plaque psoriasis or active
psoriatic arthritis in the U.S.1
About ADVANCE (PSOR-022)
ADVANCE (PSOR-022) is a Phase 3, multicenter, randomized,
placebo-controlled, double-blind study evaluating the efficacy and
safety of Otezla in patients with mild-to-moderate plaque psoriasis
(defined as BSA involvement of 2% to 15%, Psoriasis Area and
Severity Index (PASI) score of 2 to 15, sPGA score of 2 to 3). The
study randomized 595 patients 1:1 to receive Otezla (n=297) 30 mg
twice daily or placebo (n=298) for the first 16 weeks. All patients
then received Otezla during an open-label extension phase through
week 32.
The primary endpoint was the percentage of patients with sPGA
response [defined as a sPGA score of clear (0) or almost clear (1)
with at least a 2-point reduction from baseline] at week 16.
About Psoriasis
Psoriasis is a serious, chronic inflammatory disease that causes
raised, red, scaly patches to appear on the skin, typically
affecting the outside of the elbows, knees or scalp, though it can
appear on any location.2 Approximately 125 million
people worldwide have psoriasis, including around 14 million people
in Europe and more than 7.5
million people in the United
States.3,4 About 80% of those patients have
plaque psoriasis.5
About Otezla® (apremilast)
OTEZLA® (apremilast) 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.
Otezla® (apremilast) U.S.
INDICATIONS
Otezla® (apremilast) is indicated for the treatment of
adult 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.
Otezla is indicated for the treatment of adult patients with
oral ulcers associated with Behçet's Disease.
Otezla® (apremilast) U.S. 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
- Behcet's Disease: Treatment with Otezla is associated with an
increase in depression. During the phase 3 clinical trial, 1%
(1/104) reported depression or depressed mood compared to 1%
(1/103) treated with placebo. No instances of suicidal ideation or
behavior were reported in patients treated with Otezla or treated
with placebo
- Weight Decrease: Monitor body weight regularly; evaluate
unexplained or clinically significant weight loss, and consider
discontinuation of Otezla
-
- Psoriasis: During clinical trials, 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: During clinical trials, body weight loss
of 5-10% was reported in 10% (49/497) of patients taking Otezla and
in 3.3% (16/495) of patients taking placebo
- Behçet's Disease: During the phase 3 clinical trial, body
weight loss of >5% was reported in 4.9% (5/103) of patients
taking Otezla and in 3.9% (4/102) 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)
- Behçet's Disease: Adverse reactions reported in at least ≥5% of
patients taking Otezla, that occurred at a frequency at least 1%
higher than that observed in patients taking placebo, for up to 12
weeks, were (Otezla%, placebo%): diarrhea (41.3, 20.4); nausea
(19.2, 10.7); headache (14.4, 10.7); upper respiratory tract
infection (11.5, 4.9); upper abdominal pain (8.7, 1.9); vomiting
(8.7, 1.9); back pain (7.7, 5.8); viral upper respiratory tract
infection (6.7, 4.9); arthralgia (5.8, 2.9)
Use in Specific Populations
- Pregnancy: Otezla has not been studied in pregnant women.
Advise pregnant women of the potential risk of fetal loss. Consider
pregnancy planning and prevention for females of reproductive
potential. There is a pregnancy exposure registry that monitors
pregnancy outcomes in women exposed to Otezla during pregnancy.
Information about the registry can be obtained by calling
1-877-311-8972 or visiting
https://mothertobaby.org/ongoing-study/otezla/
- Lactation: There are no data on the presence of apremilast or
its metabolites in human milk, the effects of apremilast on the
breastfed infant, or the effects of the drug on milk production.
The developmental and health benefits of breastfeeding should be
considered along with the mother's clinical need for Otezla and any
potential adverse effects on the breastfed child from Otezla or
from the underlying maternal condition
- 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 Otezla® Full Prescribing
Information.
About Amgen
Amgen is committed to unlocking the
potential of biology for patients suffering from serious illnesses
by discovering, developing, manufacturing and delivering innovative
human therapeutics. This approach begins by using tools like
advanced human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages
its expertise to strive for solutions that improve health outcomes
and dramatically improve people's lives. A biotechnology pioneer
since 1980, Amgen has grown to be one of the world's leading
independent biotechnology companies, has reached millions of
patients around the world and is developing a pipeline of medicines
with breakaway potential.
For more information, visit www.amgen.com and follow us on
www.twitter.com/amgen.
Forward-Looking Statements
This news release contains forward-looking statements that are
based on the current expectations and beliefs of Amgen. All
statements, other than statements of historical fact, are
statements that could be deemed forward-looking statements,
including any statements on the outcome, benefits and synergies of
collaborations, or potential collaborations, with any other
company, including BeiGene, Ltd. or any collaboration to
manufacture therapeutic antibodies against COVID-19, or the
Otezla® (apremilast) acquisition (including anticipated
Otezla sales growth and the timing of non-GAAP EPS accretion), as
well as estimates of revenues, operating margins, capital
expenditures, cash, other financial metrics, expected legal,
arbitration, political, regulatory or clinical results or
practices, customer and prescriber patterns or practices,
reimbursement activities and outcomes, effects of pandemics or
other widespread health problems such as the ongoing COVID-19
pandemic on our business, outcomes, progress, or effects relating
to studies of Otezla as a potential treatment for COVID-19, and
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CONTACT: Amgen, Thousand Oaks
Trish Rowland, 805-447-5631
(Media)
Megan Fox, 805-447-1423 (Media)
Arvind Sood, 805-447-1060
(Investors)
1 Data on File at Amgen Inc.
2 National Psoriasis Foundation. About Psoriasis.
Available at: https://www.psoriasis.org/about-psoriasis. Accessed
September 22, 2020.
3 National Psoriasis Foundation. Statistics.
Available at: https://www.psoriasis.org/content/statistics.
Accessed September 22, 2020.
4 Ortonne JP, Prinz JC. Alefacept: a novel and
selective biologic agent for the treatment of chronic plaque
psoriasis. Eur J Dermatol. 2004;14(1):41–45.
5 National Psoriasis Foundation. Plaque Psoriasis.
Available at:
https://www.psoriasis.org/about-psoriasis/types/plaque. Accessed
September 22, 2020.
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