Celgene Corporation (NASDAQ:CELG) today announced it has
fulfilled the accelerated approval requirements for POMALYST®
(pomalidomide) based on results from MM-003, an international phase
III study of POMALYST plus low-dose dexamethasone versus high-dose
dexamethasone in relapsed/refractory multiple myeloma patients.
POMALYST, in combination with dexamethasone is approved for
patients with multiple myeloma who have received at least two prior
therapies including lenalidomide and a proteasome inhibitor and
have demonstrated disease progression on or within 60 days of
completion of the last therapy.
“There remains a significant unmet need for relapsed/refractory
multiple myeloma patients. POMALYST has been able to help thousands
of patients since its approval in 2013 and this data now confirms
its survival benefits,” said Jacqualyn A. Fouse, Ph.D., President,
Global Hematology and Oncology for Celgene. “This label update
provides important information about a key product in our
industry-leading portfolio of therapies for patients with multiple
myeloma.”
In the MM-003 study, median progression-free survival (PFS), the
primary endpoint of the study, was significantly longer with
POMALYST plus low-dose dexamethasone (3.6 months) than high-dose
dexamethasone (1.8 months: HR 0.45 two-sided 95% CI: 0.35-0.59
p<0.001). Patients in the POMALYST plus low-dexamethasone arm
had a 55% reduction in the risk of progression or death.
The pre-specified, final analysis for overall survival (OS)
showed a median OS for the POMALYST plus low-dose dexamethasone arm
of 12.4 months (95% CI: 10.4, 15.3), compared to the high-dose
dexamethasone arm of 8 months (95% CI: 6.9, 9.0). This survival
benefit was statistically significant (HR 0.70 [two-sided 95% CI:
0.54, 0.92], p=0.009) even though 53% of patients in the high-dose
dexamethasone arm had subsequently received POMALYST. The hazard
ratio of 0.70 equated to a 30% reduction in the risk of death for
patients receiving POMALYST plus low-dose dexamethasone. Median PFS
and OS were based on the assessment of an Independent Review
Adjudication Committee.
POMALYST was initially approved by the FDA in February 2013
under the agency’s accelerated approval program based on the phase
II study, MM-002.
POMALYST® (pomalidomide) is a thalidomide analogue
indicated, in combination with dexamethasone, for patients with
multiple myeloma who have received at least two prior therapies
including lenalidomide and a proteasome inhibitor and have
demonstrated disease progression on or within 60 days of completion
of the last therapy.
Important Safety Information
WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND
ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity
- POMALYST is contraindicated in pregnancy. POMALYST is a
thalidomide analogue. Thalidomide is a known human teratogen that
causes severe birth defects or embryo-fetal death. In females of
reproductive potential, obtain 2 negative pregnancy tests before
starting POMALYST treatment.
- Females of reproductive potential must use 2 forms of
contraception or continuously abstain from heterosexual sex during
and for 4 weeks after stopping POMALYST treatment.
POMALYST is only available through a restricted distribution
program called POMALYST REMS®.
Venous and Arterial
Thromboembolism
- Deep venous thrombosis (DVT), pulmonary embolism (PE),
myocardial infarction, and stroke occur in patients with multiple
myeloma treated with POMALYST. Prophylactic antithrombotic measures
were employed in clinical trials. Thromboprophylaxis is
recommended, and the choice of regimen should be based on
assessment of the patient’s underlying risk factors.
CONTRAINDICATIONS: Pregnancy
- POMALYST can cause fetal harm and is
contraindicated in females who are pregnant. If POMALYST is used
during pregnancy or if the patient becomes pregnant while taking
this drug, the patient should be apprised of the potential hazard
to a fetus
WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity
- Females of
Reproductive Potential: Must avoid pregnancy while taking
POMALYST and for at least 4 weeks after completing therapy. Must
commit either to abstain continuously from heterosexual sexual
intercourse or to use 2 methods of reliable birth control,
beginning 4 weeks prior to initiating treatment with POMALYST,
during therapy, during dose interruptions, and continuing for 4
weeks following discontinuation of POMALYST therapy. Must obtain 2
negative pregnancy tests prior to initiating therapy
- Males:
Pomalidomide is present in the semen of patients receiving the
drug. Males must always use a latex or synthetic condom during any
sexual contact with females of reproductive potential while taking
POMALYST and for up to 28 days after discontinuing POMALYST, even
if they have undergone a successful vasectomy. Males must not
donate sperm
- Blood
Donation: Patients must not donate blood during treatment
with POMALYST and for 1 month following discontinuation of POMALYST
therapy because the blood might be given to a pregnant female
patient whose fetus must not be exposed to POMALYST
POMALYST REMS® Program
Because of the embryo-fetal risk, POMALYST is available only
through a restricted program under a Risk Evaluation and Mitigation
Strategy (REMS) called “POMALYST REMS®.” Prescribers
and pharmacies must be certified with the program; patients must
sign an agreement form and comply with the requirements. Further
information about the POMALYST REMS® program is
available at www.CelgeneRiskManagement.com or by telephone
at 1-888-423-5436.
Venous and Arterial Thromboembolism: Venous
thromboembolic events (DVT and PE) and arterial thromboembolic
events (ATE) (myocardial infarction and stroke) have been observed
in patients treated with POMALYST. In Trial 2, where anticoagulant
therapies were mandated, thromboembolic events occurred in 8.0% of
patients treated with POMALYST and low dose-dexamethasone (Low-dose
Dex) vs 3.3% treated with high-dose dexamethasone. Venous
thromboembolic events (VTE) occurred in 4.7% of patients treated
with POMALYST and Low-dose Dex vs 1.3% treated with high-dose
dexamethasone. Arterial thromboembolic events include terms for
arterial thromboembolic events, ischemic cerebrovascular
conditions, and ischemic heart disease. Arterial thromboembolic
events occurred in 3.0% of patients treated with POMALYST and
Low-dose Dex vs 1.3% treated with high-dose dexamethasone. Patients
with known risk factors, including prior thrombosis, may be at
greater risk, and actions should be taken to try to minimize all
modifiable factors (e.g., hyperlipidemia, hypertension,
smoking).
Hematologic Toxicity: In trials 1 and 2 in patients who
received POMALYST + Low-dose Dex, neutropenia (46%) was the most
frequently reported Grade 3/4 adverse reaction, followed by anemia
and thrombocytopenia. Monitor patients for hematologic toxicities,
especially neutropenia. Monitor complete blood counts weekly for
the first 8 weeks and monthly therafter. Patients may require dose
interruption and/or modification.
Hepatotoxicity: Hepatic failure, including fatal cases,
has occurred in patients treated with POMALYST. Elevated levels of
alanine aminotransferase and bilirubin have also been observed in
patients treated with POMALYST. Monitor liver function tests
monthly. Stop POMALYST upon elevation of liver enzymes. After
return to baseline values, treatment at a lower dose may be
considered.
Hypersensitivity Reactions: Angioedema and severe
dermatologic reactions have been reported. Discontinue POMALYST for
angioedema, skin exfoliation, bullae, or any other severe
dermatologic reactions, and do not resume therapy.
Dizziness and Confusional State: In trials 1 and 2 in
patients who received POMALYST + Low-dose Dex, 14% experienced
dizziness and 7% a confusional state; 1% of patients experienced
Grade 3 or 4 dizziness and 3% experienced a Grade 3 or 4
confusional state. Instruct patients to avoid situations where
dizziness or confusional state may be a problem and not to take
other medications that may cause dizziness or confusional state
without adequate medical advice.
Neuropathy: In trials 1 and 2, patients who received
POMALYST + Low-dose Dex experienced neuropathy (18%) and peripheral
neuropathy (~12%). In trial 2, 2% of patients experienced Grade 3
neuropathy.
Risk of Second Primary Malignancies: Cases of acute
myelogenous leukemia have been reported in patients receiving
POMALYST as an investigational therapy outside of multiple
myeloma.
Tumor Lysis Syndrome: Tumor lysis syndrome (TLS) may
occur in patients treated with POMALYST. Patients at risk are those
with high tumor burden prior to treatment. These patients should be
monitored closely and appropriate precautions taken.
ADVERSE REACTIONS
Nearly all patients treated with POMALYST + Low-dose Dex
experienced at least one adverse reaction (99%). In trial 2, the
most common adverse reactions included neutropenia (51.3%), fatigue
and asthenia (46.7%), upper respiratory tract infection (31%),
thrombocytopenia (29.7%), pyrexia (26.7%), dyspnea (25.3%),
diarrhea (22%), constipation (21.7%), back pain (19.7%), cough
(20%), pneumonia (19.3%), edema peripheral (17.3%), peripheral
neuropathy (17.3%), bone pain (18%), nausea (15%), and muscle
spasms (15.3%). Grade 3 or 4 adverse reactions included neutropenia
(48.3%), thrombocytopenia (22%), and pneumonia (15.7%).
DRUG INTERACTIONS
Pomalidomide is primarily metabolized by CYP1A2 and CYP3A.
Pomalidomide is also a substrate for P-glycoprotein (P-gp). Avoid
the use of strong CYP1A2 inhibitors. If medically necessary to
co-administer strong inhibitors of CYP1A2 in the presence of strong
inhibitors of CYP3A4 and P-gp, reduce POMALYST dose by 50%.
Cigarette smoking may reduce pomalidomide exposure due to CYP1A2
induction. Patients should be advised that smoking may reduce the
efficacy of pomalidomide.
USE IN SPECIFIC POPULATIONS
Pregnancy: If pregnancy does occur during treatment,
immediately discontinue the drug and refer patient to an
obstetrician/gynecologist experienced in reproductive toxicity for
further evaluation and counseling. Report any suspected fetal
exposure to POMALYST to the FDA via the MedWatch program at
1-800-332-1088 and also to Celgene Corporation at
1-888-423-5436.
Nursing Mothers: It is not known if pomalidomide is
excreted in human milk. Pomalidomide was excreted in the milk of
lactating rats. Because many drugs are excreted in human milk and
because of the potential for adverse reactions in nursing infants
from POMALYST, a decision should be made whether to discontinue
nursing or to discontinue the drug, taking into account the
importance of the drug to the mother.
Pediatric Use: Safety and effectiveness of POMALYST in
patients under the age of 18 have not been established.
Geriatric Use: No dosage adjustment is required for
POMALYST based on age. Patients >65 years of age were more
likely than patients ≤65 years of age to experience pneumonia.
Renal and Hepatic Impairment: Pomalidomide is metabolized
in the liver. Pomalidomide and its metabolites are primarily
excreted by the kidneys. The influence of renal and hepatic
impairment on the safety, efficacy, and pharmacokinetics of
pomalidomide has not been evaluated. Avoid POMALYST in patients
with a serum creatinine >3.0 mg/dL. Avoid POMALYST in patients
with serum bilirubin >2.0 mg/dL and AST/ALT >3.0 x ULN.
Please see full Prescribing Information,
including Boxed WARNINGS.
About MM-003
MM-003 was a Phase III multi-center, randomized, open-label
study where POMALYST + low-dose dexamethasone therapy was compared
to high-dose dexamethasone in adult patients with relapsed and
refractory multiple myeloma, who had received at least two prior
treatment regimens, including lenalidomide and bortezomib, and
demonstrated disease progression on or within 60 days of the last
therapy. For patients receiving POMALYST + low-dose dexamathasone,
94% were refractory to lenalidomide, and 74% were refractory to
both lenalidomide and bortezomib. Patients with creatinine
clearance ≥ 45ml/min qualified for the study. A total of 455
patients were enrolled in the study: 302 in the POMALYST + low-dose
dexamethasone arm and 153 in the high-dose dexamethasone arm.
Patients in the POMALYST + low-dose dexamethasone arm were
administered 4 mg POMALYST orally on days 1 to 21 of each 28-day
cycle. Dexamethasone (40 mg) was administered once per day on days
1, 8, 15 and 22 of a 28-day cycle. Patients >75 years of age
started treatment with 20 mg dexamethasone using the same schedule.
For the high-dose dexamethasone arm, dexamethasone (40 mg) was
administered once per day on days 1 through 4, 9 through 12, and 17
through 20 of a 28-day cycle. Patients >75 years of age started
treatment with 20 mg dexamethasone using the same schedule.
Treatment continued until patients had disease progression.
About POMALYST®
POMALYST is a thalidomide analogue indicated in combination with
dexamethasone for patients with multiple myeloma who have received
at least two prior therapies including lenalidomide and a
proteasome inhibitor and have demonstrated disease progression on
or within 60 days of completion of the last therapy.
Please see full Prescribing Information,
including Boxed WARNINGS.
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.
POMALYST® is a registered trademark of Celgene Corporation.
Forward-Looking Statements
This press release may contain 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 Celgene:Investors:(908)
673-9628investors@celgene.comorMedia:(908)
673-2275media@celgene.com
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