Celgene Corporation (NASDAQ:CELG) today announced it has received a
Paragraph IV Certification Letter advising that Natco Pharma Limited of
Hyderabad, India, submitted an Abbreviated New Drug Application (ANDA)
to the U.S. Food and Drug Administration (FDA). The application requests
authorization to manufacture and market generic versions of REVLIMID
(lenalidomide) 5, 10, 15 and 25 mg capsules in the United States.
Celgene intends to vigorously enforce its extensive intellectual
property rights for REVLIMID and plans to file a complaint alleging
infringement within the required 45-day response period. REVLIMID is
currently protected by 12 issued patents listed in the FDAs Approved
Drug Products List (Orange Book) and has additional patent applications
pending. The issued patents comprise composition of matter, polymorph
and method of use claims as well as claims related to Celgenes
proprietary RevAssist system. In order for Natco to
avoid liability, all patent claims in the suit must be deemed invalid,
not infringed, unenforceable, or expired.
About REVLIMID
REVLIMID is an IMiDs compound. REVLIMID and
other IMiDs continue to be evaluated in over 100 clinical trials in a
broad range of hematological and oncological conditions. The IMiDs
pipeline is covered by a comprehensive intellectual property estate of
issued and pending patent applications in the US, EU and other regions,
including composition-of- matter and use patents.
REVLIMID is approved in combination with dexamethasone for the treatment
of patients with multiple myeloma who have received at least one prior
therapy in nearly 50 countries, encompassing Europe, the Americas, the
Middle-East and Asia, and in combination with dexamethasone for the
treatment of patients whose disease has progressed after one therapy in
Australia and New Zealand.
REVLIMID is also approved in the United States, Canada and several Latin
American countries, as well as Malaysia, Israel, Japan, Australia and
New Zealand for transfusion-dependent anemia due to low- or
intermediate-1-risk MDS associated with a deletion 5q cytogenetic
abnormality with or without additional cytogenetic abnormalities.
Marketing Authorization Applications are currently being evaluated in a
number of other countries.
REVLIMID (lenalidomide) in combination with dexamethasone is indicated
for the treatment of multiple myeloma patients who have received at
least one prior therapy.
REVLIMID (lenalidomide) is indicated for patients with
transfusion-dependent anemia due to Low- or Intermediate-1risk
myelodysplastic syndromes (MDS) associated with a deletion 5q
cytogenetic abnormality with or without additional cytogenetic
abnormalities.
Important Safety Information
WARNINGS:
1. POTENTIAL FOR HUMAN BIRTH DEFECTS.
Lenalidomide is an analogue of thalidomide. Thalidomide is a known
human teratogen that causes severe life-threatening human birth defects.
If lenalidomide is taken during pregnancy, it may cause birth defects or
death to an unborn baby. Females should be advised to avoid pregnancy
while taking REVLIMID (lenalidomide).
Male Patients: It is not known whether lenalidomide is present
in the semen of patients receiving the drug. Therefore, males
receiving REVLIMID (lenalidomide) must always use a
latex condom during any sexual contact with females of childbearing
potential even if they have undergone a successful vasectomy.
Special Prescribing Requirements
Because of this potential toxicity and to avoid fetal exposure to
REVLIMID (lenalidomide), REVLIMID (lenalidomide)
is only available under a special restricted distribution program. In
the U.S., this program is called RevAssist.
Under this program, only prescribers and pharmacists registered with the
program can prescribe and dispense the product. In addition, REVLIMID
(lenalidomide) must only be dispensed to patients who are
registered and meet all the conditions of the RevAssist
program.
2. HEMATOLOGIC TOXICITY (NEUTROPENIA
AND THROMBOCYTOPENIA).
This drug is associated with significant neutropenia and
thrombocytopenia. Eighty percent of patients with del 5q
myelodysplastic syndromes had to have a dose delay/reduction during the
major study. Thirty-four percent of patients had to have a second dose
delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of
patients enrolled in the study. Patients on therapy for del 5q
myelodysplastic syndromes should have their complete blood counts
monitored weekly for the first 8 weeks of therapy and at least monthly
thereafter. Patients may require dose interruption and/or reduction.
Patients may require use of blood product support and/or growth factors.
(see DOSAGE and ADMINISTRATION)
3. DEEP VENOUS THROMBOSIS AND
PULMONARY EMBOLISM.
This drug has demonstrated a significantly increased risk of deep
venous thrombosis (DVT) and pulmonary embolism (PE) in patients with
multiple myeloma who were treated with REVLIMID
(lenalidomide) combination therapy. Patients and physicians are advised
to be observant for the signs and symptoms of thromboembolism. Patients
should be instructed to seek medical care if they develop symptoms such
as shortness of breath, chest pain, or arm or leg swelling. It is not
known whether prophylactic anticoagulation or antiplatelet therapy
prescribed in conjunction with REVLIMID
(lenalidomide) may lessen the potential for venous thromboembolic
events. The decision to take prophylactic measures should be done
carefully after an assessment of an individual patients underlying risk
factors.
You can get the information about REVLIMID
(lenalidomide) and the RevAssist program on
the Internet at www.REVLIMID.com
or by calling the manufacturers toll-free number at 1-888-423-5436.
ADDITIONAL WARNINGS: HEMATOLOGIC TOXICITY
Multiple Myeloma
In the pooled multiple myeloma studies, Grade 3 and 4 hematologic
toxicities were more frequent in patients treated with the combination
of REVLIMID (lenalidomide) and dexamethasone than in patients treated
with dexamethasone alone
Patients on therapy should have their complete blood counts
monitored every 2 weeks for the first 12 weeks and then monthly
thereafter
Patients may require dose interruption and/or dose reduction
CONTRAINDICATIONS:
Pregnancy Category X:
Lenalidomide is contraindicated in pregnant women and women capable of
becoming pregnant. When there is no alternative, females of
childbearing potential may be treated with lenalidomide provided
adequate precautions are taken to avoid pregnancy
Hypersensitivity:
REVLIMID (lenalidomide) is contraindicated in any patients
who have demonstrated hypersensitivity to the drug or its components
PRECAUTIONS:
Angioedema, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis:
Angioedema and serious dermatologic reactions including
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
have been reported. These events can be fatal. Patients with a prior
history of Grade 4 rash associated with thalidomide treatment should
not receive REVLIMID (lenalidomide). REVLIMID
(lenalidomide) interruption or discontinuation should be considered
for Grade 2-3 skin rash. REVLIMID (lenalidomide) must be
discontinued for angioedema, Grade 4 rash, exfoliative or bullous
rash, or if SJS or TEN is suspected, and should not be resumed
following discontinuation for these reactions
Tumor Lysis Syndrome;
Lenalidomide has antineoplastic activity and therefore the
complications of tumor lysis syndrome may occur. The patients at risk
of tumor lysis syndrome are those with high tumor burden prior to
treatment. These patients should be monitored closely and appropriate
precautions taken
Renal impairment:
Since lenalidomide is primarily excreted unchanged by the kidney,
adjustments to the starting dose of REVLIMID
(lenalidomide) are recommended to provide appropriate drug exposure in
patients with moderate or severe (CLcr > 60 mL/min) renal
impairment and in patients on dialysis
Because elderly patients are more likely to have decreased renal
function, care should be taken in dose selection, and it would be
prudent to monitor renal function
Nursing mothers: It is not known whether REVLIMID
(lenalidomide) is excreted in human milk.
Because of the potential for adverse reactions in nursing infants, a
decision should be made whether to discontinue nursing or the drug,
taking into account the importance of the drug to the mother
ADVERSE REACTIONS:
Multiple Myeloma
In the REVLIMID (lenalidomide)/dexamethasone treatment
group, 151 patients (45%) underwent at least one dose interruption
with or without a dose reduction of REVLIMID (lenalidomide)
compared to 21% in the placebo/dexamethasone treatment group
Of these patients who had one dose interruption with or without a dose
reduction, 50% in the REVLIMID (lenalidomide)/dexamethasone
treatment group underwent at least one additional dose interruption
with or without a dose reduction compared to 21% in the
placebo/dexamethasone treatment group
Most adverse events and Grade 3/4 adverse events were more frequent in
MM patients who received the combination of REVLIMID
(lenalidomide)/dexamethasone compared to placebo/dexamethasone
Other adverse events reported in multiple myeloma patients (REVLIMID
(lenalidomide)/dexamethasone vs dexamethasone/placebo): constipation
(39% vs 19%), fatigue (38% vs 37%), insomnia (32% vs 37%), muscle cramp
(30% vs 21%), diarrhea (29% vs 25%), neutropenia (28% vs 5%), anemia
(24% vs 17%), asthenia (23% vs 25%), pyrexia (23% vs 19%), nausea (22%
vs 19%), headache (21% vs 21%), peripheral edema (21% vs 19%), dizziness
(21% vs 15%), dyspnea (20% vs 15%), tremor (20% vs 7%), decreased weight
(18% vs 14%), thrombocytopenia (17% vs 10%), rash (16% vs 8%), back pain
(15% vs 14%), hyperglycemia (15% vs 14%), and muscle weakness (15% vs
15%).
Myelodysplastic Syndromes
Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were
the most frequently reported adverse events observed in the del 5q MDS
population
Other adverse reactions reported in del 5q MDS patients (REVLIMID
(lenalidomide)): diarrhea (49%), pruritus (42%), rash
(36%), fatigue (31%), constipation (24%), nausea (24%), nasopharyngitis
(23%), arthralgia (22%), pyrexia (21%), back pain (21%), peripheral
edema (20%), cough (20%), dizziness (20%), headache (20%), muscle cramp
(18%), dyspnea (17%), and pharyngitis (16%).
DOSAGE AND ADMINISTRATION:
Dosing is continued or modified based upon clinical and laboratory
findings. Dosing modifications are recommended to manage Grade 3 or 4
neutropenia or thrombocytopenia or other Grade 3 or 4 toxicity judged
to be related to REVLIMID (lenalidomide)
For other Grade 3 or 4 toxicities judged to be related to REVLIMID(lenalidomide),
hold treatment and restart at next lower dose level when toxicity has
resolved to less than or equal to Grade 2
Please see full Prescribing Information, including Boxed WARNINGS,
CONTRAINDICATIONS, PRECAUTIONS, and ADVERSE REACTIONS.
About Multiple Myeloma
Multiple myeloma (also known as myeloma or plasma cell myeloma) is a
cancer of the blood in which malignant plasma cells are overproduced in
the bone marrow. Plasma cells are white blood cells that help produce
antibodies called immunoglobulins that fight infection and disease.
However, most patients with multiple myeloma have cells that produce a
form of immunoglobulin called paraprotein (or M protein) that does not
benefit the body. In addition, the malignant plasma cells replace normal
plasma cells and other white blood cells important to the immune system.
Multiple myeloma cells can also attach to other tissues of the body,
such as bone, and produce tumors. The cause of the disease remains
unknown.
About Celgene Corporation
Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global biopharmaceutical company engaged primarily in the
discovery, development and commercialization of novel therapies for the
treatment of cancer and inflammatory diseases through gene and protein
regulation. For more information, please visit the companys Web site at www.celgene.com.
This release contains certain forward-looking statements which
involve known and unknown risks, delays, uncertainties and other factors
not under the Companys control, which may cause actual results,
performance or achievements of the Company to be materially different
from the results, performance or other expectations implied by these
forward-looking statements. These factors include results of current or
pending research and development activities, actions by the FDA and
other regulatory authorities, and those factors detailed in the
Companys filings with the Securities and Exchange Commission such as
10K, 10Q and 8K reports.
Source: Business Wire
