Improvements in the severity of preexisting
nail, scalp and palmoplantar psoriasis achieved at week 16 were
maintained in OTEZLA responders through week 52 in ESTEEM 2
OTEZLA improved the severity of palmoplantar
psoriasis at week 16 in a subset of patients across three
trials
Long-term safety profile for up to 104 weeks in
ESTEEM 1 was consistent with previously reported data from OTEZLA
clinical trial programs, with no new safety signals and no
clinically meaningful changes in laboratory values
Celgene Corporation (NASDAQ: CELG) today announced that results
from long-term efficacy and safety analyses of the ESTEEM phase III
clinical trial program of Otezla® (apremilast) were presented at
the 73rd Annual Meeting of the American Academy of Dermatology
(AAD) in San Francisco, California. OTEZLA is the Company’s oral,
selective inhibitor of phosphodiesterase 4 (PDE4) approved for the
treatment of patients with moderate to severe plaque psoriasis who
are candidates for phototherapy or systemic therapy and for the
treatment of adults with active psoriatic arthritis.
In ESTEEM 1 and 2, patients were randomized to treatment with
OTEZLA 30 mg twice daily or placebo for the first 16 weeks. At week
16, patients either continued on OTEZLA or were switched from
placebo to OTEZLA 30 mg twice daily through week 32. Patients
initially randomized to OTEZLA who achieved a Psoriasis Area and
Severity Index (PASI)-75 response (ESTEEM 1) or PASI-50 response
(ESTEEM 2) at week 32 were then re-randomized to either OTEZLA 30
mg twice daily or placebo.
“Long-term data are critical in psoriasis, since patients may
deal with this disease throughout their lives,” said Jeffrey
Crowley, M.D., Bakersfield Dermatology, Bakersfield, CA. “Having
two-year safety results along with data showing that OTEZLA can
provide long-term improvements in difficult-to-treat symptoms can
be helpful for dermatologists and patients who are looking for
different treatment options.”
ESTEEM 2: 52-Week Data Observed in Patients with Nail, Scalp
and Palmoplantar Involvement
An analysis of data from ESTEEM 2 presented at AAD showed
sustained improvements at week 52 among PASI-50 responders
(patients who achieved a 50 percent reduction in PASI at week 32)
in difficult-to-treat areas such as nails, scalp and the palms of
the hands and soles of the feet (known as palmoplantar
psoriasis).
Among patients who had nail psoriasis at baseline with a Nail
Psoriasis Severity Index (NAPSI) greater than or equal to one, 45
percent (78/175) of those treated with OTEZLA 30 mg twice daily had
at least a 50 percent improvement in NAPSI (NAPSI-50) at week 16,
compared with 19 percent (17/91) of those treated with placebo
(P<0.0001). NAPSI-50 achievement was generally maintained for up
to 52 weeks in patients (69 percent, n=35) who received OTEZLA at
baseline who were PASI-50 responders.
Of those patients who had moderate to very severe scalp
psoriasis at baseline, 41 percent (72/176) of those treated with
OTEZLA 30 mg twice daily had a Scalp Physician Global Assessment
(ScPGA) score of clear (zero) or minimal (one) at week 16, compared
with 17 percent (16/93) of those treated with placebo
(P<0.0001). ScPGA score of zero or one achievement was generally
maintained for up to 52 weeks in patients (63 percent, n=32) who
received OTEZLA at baseline who were PASI-50 responders.
Among patients who had moderate to severe psoriasis on their
palms and feet at baseline, 65 percent (17/26) of those treated
with OTEZLA 30 mg twice daily had a Palmoplantar Psoriasis
Physician Global Assessment (PPPGA) score of clear (zero) or almost
clear (one) at week 16, compared with 31 percent (5/16) of those
treated with placebo (P=0.0315). PPPGA score of zero or one
achievement was sustained up to week 52 (n=4 of 4 patients) in
patients randomized to OTEZLA who were PASI-50 responders at week
32.
PSOR-005, ESTEEM 1 and ESTEEM 2: 16-Week Palmoplantar
Data
An analysis of PSOR-005, ESTEEM 1 and ESTEEM 2 found that OTEZLA
improved palmoplantar psoriasis in a subset of patients with
moderate to severe chronic plaque psoriasis who had palmoplantar
involvement.
Of those patients who had any palmoplantar psoriasis at baseline
(PPPGA score of one or greater, n=427 across the three studies – 49
in PSOR-005, 254 in ESTEEM 1 and 124 in ESTEEM 2), a higher
percentage of patients treated with OTEZLA 30 mg twice daily had
PPPGA reduced to clear or almost clear compared with placebo at
week 16 in all three trials [PSOR-005: 70 percent (19/27) vs. 32
percent (7/22), respectively, P=0.0072; ESTEEM 1: 63 percent
(107/169) vs. 45 percent (38/85), respectively, P=0.0047; ESTEEM 2:
71 percent (55/78) vs. 37 percent (17/46), respectively,
P=0.0003].
Among patients who had moderate to severe palmoplantar psoriasis
at baseline (PPPGA score of three or greater) (n=144 across the
three studies — 19 in PSOR-005, 83 in ESTEEM 1 and 42 in ESTEEM 2),
a higher percentage of patients treated with OTEZLA 30 mg twice
daily had PPPGA reduced to clear or almost clear compared with
placebo at week 16 in PSOR-005 [67 percent (6/9) vs. 20 percent
(2/10), respectively, P=0.0397] and ESTEEM 2 [65 percent (17/26)
vs. 31 percent (5/16), respectively, P=0.0315]. There was no
significant difference between the OTEZLA and placebo groups at
week 16 in ESTEEM 1 [39 percent (22/57) vs. 31 percent (8/26),
respectively, P=0.4912].
ESTEEM 1: Two-Year Safety Data
Long-term (104-week) results from the ESTEEM 1 trial showed that
no new safety signals were identified in patients treated with
OTEZLA 30 mg twice daily for up to two years (844 patients were
randomized, 444 continued in the second year).
As with adverse events (AEs) reported during the first 52 weeks
of exposure, most AEs reported during weeks 52 to 104 were mild or
moderate in severity and did not lead to discontinuation. The most
frequently reported AEs during the placebo-controlled period and
the OTEZLA-exposure periods were diarrhea, upper respiratory tract
infection, nausea, nasopharyngitis, tension headache and
headache.
The exposure adjusted incidence rate (EAIR) for serious AEs did
not increase with longer OTEZLA exposure, compared with the
placebo-controlled period. There were no clinically meaningful
changes in laboratory measurements identified over the OTEZLA
104-week exposure period. Incidence rates of major cardiac events,
solid tumors, hematological malignancies and serious infections
were comparable between the placebo and OTEZLA arms during the
placebo-controlled period. No increase in incidence rates was noted
with longer-term exposure to OTEZLA between weeks 52 to 104.
About ESTEEM
ESTEEM 1 and 2 are two large pivotal phase III randomized,
placebo-controlled studies evaluating OTEZLA in patients with a
diagnosis of moderate to severe plaque psoriasis for at least 12
months prior to screening, and who were also candidates for
phototherapy and/or systemic therapy. Approximately 1,250 patients
were randomized 2:1 to receive either OTEZLA 30 mg twice daily or
placebo after an initial five-day titration period, for the first
16 weeks, followed by a maintenance phase from weeks 16-32 in which
placebo patients were switched to OTEZLA 30 mg twice daily through
week 32, and a randomized withdrawal phase for responders from week
32 to week 52 based on their initial OTEZLA randomization and
Psoriasis Area and Severity Index (PASI)–75 response (ESTEEM 1) or
(PASI)-50 (ESTEEM2).
About PSOR-005
PSOR-005 is a phase IIb, multicenter, randomized,
placebo-controlled, dose-ranging study evaluating OTEZLA in
patients with a diagnosis of moderate to severe plaque psoriasis
for at least six months prior to screening, and who are also
candidates for phototherapy and/or systemic therapy. 352 patients
were randomized 1:1:1:1 to receive oral placebo or OTEZLA 10, 20,
or 30 mg twice daily after an initial five-day titration period,
for the first 16 weeks, followed by a maintenance phase from weeks
16-24 in which placebo patients were randomly switched to OTEZLA 20
mg or 30 mg twice daily through week 24.
About OTEZLA
OTEZLA 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 with psoriasis or psoriatic
arthritis is not well defined.
OTEZLA was approved on March 21, 2014 by the U.S Food and Drug
Administration (FDA) for the treatment of adults with active
psoriatic arthritis and on September 23, 2014 for the treatment of
patients with moderate to severe plaque psoriasis who are
candidates for phototherapy or systemic therapy. OTEZLA was also
approved on January 16, 2015 by the European Commission (EC) in two
therapeutic indications:
- For the treatment of moderate-to-severe
chronic plaque psoriasis in adult patients who failed to respond to
or who have a contraindication to, or are intolerant to other
systemic therapy including cyclosporine, methotrexate or psoralen
and ultraviolet-A light (PUVA)
- Alone or in combination with Disease
Modifying Antirheumatic Drugs (DMARDs), for the treatment of active
psoriatic arthritis (PsA) in adult patients who have had an
inadequate response or who have been intolerant to a prior DMARD
therapy
Important Safety Information (based on US labeling)
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
Depression: Treatment with OTEZLA is associated with an increase
in adverse reactions of depression. During clinical trials, 1.3%
(12/920) of patients treated with OTEZLA reported depression
compared to 0.4% (2/506) on placebo; 0.1% (1/1308) of OTEZLA
patients discontinued treatment due to depression compared with
none on placebo (0/506). 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.
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.
Weight Decrease: 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. Monitor body weight regularly;
evaluate unexplained or clinically significant weight loss, and
consider discontinuation of OTEZLA.
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 (eg, rifampin, phenobarbital, carbamazepine,
phenytoin) is not recommended.
Adverse Reactions
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).
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 Psoriasis
Psoriasis is an immune-mediated, non-contagious chronic
inflammatory skin disorder of unknown cause. The disorder is a
chronic recurring condition which varies in severity from minor
localized patches to complete body coverage. Plaque psoriasis is
the most common type of psoriasis. About 80 percent of people who
develop psoriasis have plaque psoriasis, which appears as patches
of raised, reddish skin covered by silvery-white scales. These
patches, or plaques, frequently form on the elbows, knees, lower
back, and scalp. Psoriasis occurs nearly equally in males and
females. An estimated 125 million people worldwide have psoriasis.
To learn more about the role of PDE4 in inflammatory diseases, go
to www.discoverpde4.com.
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 gene and protein regulation. For more information, please
visit www.celgene.com. Follow Celgene on Twitter @Celgene, and on
Pinterest and LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements, which
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
statements are based on management’s current plans, estimates,
assumptions and projections, and speak only as of the date they are
made. We undertake no obligation to update any forward-looking
statement in light of new information or future events, except as
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 other reports filed with the Securities and
Exchange Commission.
For inquiries, please contact:Celgene
CorporationInvestors:Patrick E. Flanigan III, 908-673-9969Vice
President, Investor RelationsorMedia:Catherine Cantone,
732-564-3592Director, Corporate Communications
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