Celgene plans to submit sNDA by end of 2019
Celgene plans additional studies with the AIDS
Malignancy Consortium in U.S. and sub-Saharan Africa
Celgene Corporation (NASDAQ:CELG) today announced that the U.S.
Food and Drug Administration (FDA) has granted Breakthrough Therapy
designation to POMALYST® (pomalidomide) for the treatment of
patients with human immunodeficiency virus (HIV)-positive Kaposi
sarcoma who have previously received systemic chemotherapy, as well
as patients with HIV‐negative Kaposi’s sarcoma.
Kaposi sarcoma is a multicentric tumor caused by Kaposi
sarcoma-associated herpesvirus, also called human herpesvirus-8.
Patients suffer multiple lesions on the skin and oral mucosa, and
at times other organs such as the lungs or gastrointestinal mucosa.
Kaposi sarcoma most commonly arises in persons infected with HIV.
There is a substantial need for new treatments because there are no
approved therapies for HIV-positive patients who are refractory to
or intolerant of systemic chemotherapy. Although the use of
combination anti-retroviral treatments (cART or HAART) has reduced
the incidence of advanced Kaposi sarcoma in the United States,
there are still nearly 2000 new cases each year. The disease is
more highly prevalent in areas of the world where HIV treatments
are less available, such as sub-Saharan Africa, and in some
countries is the most common tumor in men overall.
“The encouraging news of the FDA Breakthrough Therapy
designation for POMALYST in Kaposi sarcoma reflects the urgency in
accelerating the development of therapies to address diseases of
this type,” said Jay Backstrom, M.D., Chief Medical Officer for
Celgene. “We will continue to work closely with the agency to move
this program forward for patients with this rare and serious
cancer.”
The Breakthrough Therapy designation was granted by the FDA on
the basis of the results of a clinical study performed under a
Cooperative Research and Development Agreement (CRADA) by a team
led by Dr. Robert Yarchoan, of the HIV and AIDS Malignancy Branch
within the Center for Cancer Research of the National Cancer
Institutes (NCI). The results of that study, published in the
Journal of Clinical Oncology (MN Polizzotto et al, JCO, 2016, 34,
4125-31), evaluated POMALYST in patients with Kaposi sarcoma, with
or without HIV infection, many of whom had received prior cytotoxic
chemotherapy.
According to the FDA, Breakthrough Therapy designation is
intended to expedite the development and review of medicines with
early evidence of potential clinical benefit in serious
diseases.
Celgene plans to submit a supplemental New Drug Application for
POMALYST in this disease area by the end of 2019.
Celgene also has two additional studies planned in this disease.
In partnership with the AIDS Malignancy Consortium (AMC), a U.S.
multicenter study will be performed to confirm and extend the
results of the NCI study. The AMC is also sponsoring a second study
in sub-Saharan Africa, where Kaposi sarcoma continues to be a
serious problem. This program is a part of the Celgene Global
Health effort to discover and develop new drugs for diseases that
affect patients in the lower- and middle-income countries where
health systems and medical resources are less advanced.
POMALYST is not approved for Kaposi sarcoma in any country.
About POMALYST
POMALYST is one of Celgene’s IMiD® agents - proprietary small
molecule, orally-available compounds for the treatment of some
blood cancers. IMiD agents are hypothesized to have multiple
mechanisms of action and have become a foundation of multiple
myeloma research, with a growing number of studies exploring these
compounds in different settings and diseases.
U.S. Safety Information
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 4 weeks 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.
- Severe
Cutaneous Reactions Including Hypersensitivity
Reactions: Angioedema and severe cutaneous
reactions including Stevens-Johnson Syndrome (SJS), toxic epidermal
necrolysis (TEN), and drug reaction with eosinophilia and systemic
symptoms (DRESS) have been reported. DRESS may present with a
cutaneous reaction (such as rash or exfoliative dermatitis),
eosinophilia, fever, and/or lymphadenopathy with systemic
complications such as hepatitis, nephritis, pneumonitis,
myocarditis, and/or pericarditis. Discontinue POMALYST for
angioedema, skin exfoliation, bullae, or any other severe cutaneous
reactions such as SJS, TEN or DRESS, 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
The most common adverse reactions for POMALYST (≥30%) included
fatigue and asthenia, neutropenia, anemia, constipation, nausea,
diarrhea, dyspnea, upper-respiratory tract infections, back pain,
and pyrexia.
In the phase III trial, nearly all patients treated with
POMALYST + low-dose dex experienced at least one adverse reaction
(99%). Adverse reactions (≥15% in the POMALYST + low-dose dex arm
and ≥2% higher than control) 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% in the POMALYST
+ low-dose dex arm and ≥1% higher than control) 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 child, 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 a breastfed child from
POMALYST, advise women not to breastfeed 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 Global Health
Celgene Global Health (CGH) is a dedicated R&D unit of
Celgene committed to discovering, developing and delivering novel
drugs for Diseases of the Developing World (DDWs). Collaborating
with non-profit and academic institutions around the globe, CGH has
utilized the company’s library of more than 400,000 compounds to
evaluate candidates for drug development for DDWs. More than ten
discovery and development programs are ongoing in several disease
areas such as malaria and tuberculosis. For more information, visit
https://www.celgene.com/responsibility/global-health/
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 the Company's website at www.celgene.com. Follow Celgene
on Social Media: @Celgene, Pinterest, LinkedIn, Facebook 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. Celgene undertakes 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, including factors
related to the proposed transaction between Bristol-Myers Squibb
and Celgene, such as, but not limited to, the risks that:
management’s time and attention is diverted on transaction related
issues; disruption from the transaction makes it more difficult to
maintain business, contractual and operational relationships; legal
proceedings are instituted against Bristol-Myers Squibb, Celgene or
the combined company could delay or prevent the proposed
transaction; and Bristol-Myers Squibb, Celgene or the combined
company is unable to retain key personnel
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