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Celgene Corporation Announces Positive Results from the Pivotal Phase III 'OPTIMISMM' Study of POMALYST/IMNOVID® for the Treatment of Relapsed or Refractory Multiple Myeloma

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Study met its primary endpoint demonstrating significant improvement
in progression-free survival (PFS) with POMALYST
®/IMNOVID®
in combination with bortezomib and dexamethasone (PVd) compared with
bortezomib and low-dose dexamethasone

Celgene Corporation (NASDAQ:CELG) today announced that the Phase III,
randomized, open-label, international clinical study, OPTIMISMM,
achieved its primary endpoint, showing a statistically significant and
clinically meaningful improvement in progression-free survival (PFS) for
the pomalidomide arm versus the comparator arm.

OPTIMISMM evaluated the efficacy and safety of POMALYST/IMNOVID
(pomalidomide) plus bortezomib and low-dose dexamethasone (PVd) versus
bortezomib and low-dose dexamethasone in patients with
relapsed/refractory multiple myeloma. It is the only phase III trial to
investigate a triplet combination in patients who have all received
prior lenalidomide (REVLIMID®), a population for which there
is a growing unmet medical need.

"The OPTIMISMM results confirm the expanding role of pomalidomide in
previously treated multiple myeloma patients," said Paul Richardson,
M.D., Clinical Program Leader and Director of Clinical Research, Jerome
Lipper Multiple Myeloma Center at the Dana Farber Cancer Institute, RJ
Corman Professor of Medicine, Harvard Medical School and principal
investigator of the study. "We see the PVd combination as an important
step in improving care, and especially for patients previously treated
with lenalidomide in this setting."

In the study, the safety profile was consistent with previously reported
data. Detailed data from OPTIMISMM will be presented at future medical
meetings.

The combination of POMALYST/IMNOVID, bortezomib and low-dose
dexamethasone is not currently approved for use.

About POMALYST/IMNOVID

Indication

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 risk to a fetus.

WARNINGS AND PRECAUTIONS

  • Embryo-Fetal Toxicity & Females of
    Reproductive Potential: See Boxed WARNINGS
    • 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 4
      weeks 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: See Boxed WARNINGS
    • Prescribers and pharmacies must be certified with the POMALYST
      REMS
      program by enrolling and complying with the REMS
      requirements; pharmacies must only dispense to patients who are
      authorized to receive POMALYST. Patients must sign a
      Patient-Physician Agreement Form and comply with REMS
      requirements; female patients of reproductive potential who are
      not pregnant must comply with the pregnancy testing and
      contraception requirements and males must comply with
      contraception 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: See
    Boxed WARNINGS.
    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). Thromboprophylaxis is recommended, and the
    choice of regimen should be based on assessment of the patient's
    underlying risk factors.
  • Increased Mortality with Pembrolizumab:
    In clinical trials in patients with multiple myeloma, the addition of
    pembrolizumab to a thalidomide analogue plus dexamethasone resulted in
    increased mortality. Treatment of patients with multiple myeloma with
    a PD-1 or PD-L1 blocking antibody in combination with a thalidomide
    analogue plus dexamethasone is not recommended outside of controlled
    clinical trials.
  • Hematologic Toxicity:
    Neutropenia (46%) was the most frequently reported Grade 3/4 adverse
    reaction in patients taking POMALYST in clinical trials, followed by
    anemia and thrombocytopenia. Monitor complete blood counts weekly for
    the first 8 weeks and monthly thereafter. 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 patients taking POMALYST in clinical trials, 14% experienced
    dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or
    4). 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 patients
    taking POMALYST in clinical trials, 18% experienced neuropathy (2%
    Grade 3 in one trial) and 12% peripheral neuropathy.
  • 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 (TLS): 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%). The most common adverse reactions
(≥15%) 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%), bone pain (18%), edema
peripheral (17.3%), peripheral neuropathy (17.3%), muscle spasms
(15.3%), and nausea (15%). Grade 3 or 4 adverse reactions (≥15%)
included neutropenia (48.3%), thrombocytopenia (22%), and pneumonia
(15.7%).

DRUG INTERACTIONS

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2.
Consider alternative treatments. If a strong CYP1A2 inhibitor must be
used, reduce POMALYST dose by 50%.

USE IN SPECIFIC POPULATIONS

  • Pregnancy: See Boxed WARNINGS. 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. There is
    a POMALYST pregnancy exposure registry that monitors pregnancy
    outcomes in females exposed to POMALYST during pregnancy as well as
    female partners of male patients who are exposed to POMALYST. This
    registry is also used to understand the root cause for the pregnancy.
    Report any suspected fetal exposure to POMALYST to the FDA via the
    MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at
    1-888-423-5436.
  • Lactation: There is no
    information regarding the presence of pomalidomide in human milk, the
    effects of POMALYST on the breastfed infant, or the effects of
    POMALYST on milk production. 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 breastfed infants
    from POMALYST, advise a nursing woman to discontinue breastfeeding
    during treatment with POMALYST.
  • Pediatric Use: Safety and
    effectiveness have not been established in pediatric patients.
  • 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 Impairment: Reduce
    POMALYST dose by 25% in patients with severe renal impairment
    requiring dialysis. Take dose of POMALYST following hemodialysis on
    hemodialysis days.
  • Hepatic Impairment: Reduce
    POMALYST dose by 25% in patients with mild to moderate hepatic
    impairment and 50% in patients with severe hepatic impairment.
  • Smoking Tobacco: Advise
    patients that smoking may reduce the efficacy of POMALYST. Cigarette
    smoking reduces the AUC of pomalidomide by 32% by CYP1A2 induction.

Please see full Prescribing
Information
, including Boxed WARNINGS.

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global biopharmaceutical 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: @CelgenePinterestLinkedInFacebook and YouTube.

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 our other reports filed with the Securities and
Exchange Commission.

All registered trademarks are owned by Celgene Corporation.

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