Oral REVLIMID is approved for treatment until disease progression
BOUDRY, Switzerland--(BUSINESS WIRE)--
Celgene International Sàrl, a wholly owned subsidiary of Celgene
Corporation (NASDAQ: CELG), today announced that the European Commission
(EC) has approved REVLIMID® (lenalidomide) for the treatment
of adult patients with previously untreated multiple myeloma who are not
eligible for transplant.
The REVLIMID Marketing Authorisation has been updated to include this
new indication in multiple myeloma, building upon the already approved
indication of REVLIMID in combination with dexamethasone for the
treatment of multiple myeloma in adult patients who have received at
least one prior therapy.
Multiple myeloma is a persistent and life-threatening blood cancer that
is characterised by tumour proliferation and suppression of the immune
system.1 It is a rare but deadly disease: around 38,900
people were newly diagnosed with multiple myeloma in Europe in 2012, and
24,300 people died from the disease in the same year.2 On
average, multiple myeloma is diagnosed in people 65-74 years of age,3
and the majority of newly diagnosed patients may not be eligible for
more aggressive treatment options such as high-dose chemotherapy with
stem cell transplant.4
Professor Thierry Facon, Services des Maladies du Sang, Hôpital Claude
Huriez, and CHRU Lille, France, says: "Having a new treatment option now
available for patients newly diagnosed with multiple myeloma is a real
step forward. Treating patients continuously until disease progression
is supported by several clinical studies, and will have an important
impact on how we manage the disease over the long-term."
"We are very pleased that physicians can now offer their patients a new
and different treatment option," said Tuomo Pätsi, President of Celgene
in Europe, the Middle East and Africa (EMEA). "Multiple myeloma is rare,
but it is devastating for those who have it, and it has a major impact
on their friends and family too. We have seen significant progress in
the treatment of the disease over the years, with an improvement of more
than 50% in 5-year survival rates, but there continues to be a need for
innovative new approaches to turn deadly diseases, like this one, into
manageable, long-term, chronic conditions."
The EC decision in newly diagnosed multiple myeloma was based on the
results of two pivotal studies: MM-020 (also known as the FIRST trial)
The FIRST study, MM-020,5 was one of the largest phase III,
multi-centre, open-label, randomised studies in patients newly
diagnosed with multiple myeloma and not eligible for stem cell
transplantation, including 1,623 patients. It compared lenalidomide
plus dexamethasone administered in 28-day cycles until disease
progression (Rd), with Rd for 72 weeks (18 cycles; Rd18) and
melphalan-prednisone-thalidomide (MPT) for 72 weeks. Progression-free
survival (PFS; study primary endpoint) was significantly improved in
patients treated continuously with Rd, compared with those receiving
MPT (primary comparison, p < 0.0001) or Rd18 (p < 0.0001). Median overall
survival (OS) in patients receiving Rd continuous therapy was 58.9
months, vs. 48.5 months for patients treated with MPT (HR 0.75; 95% CI
0.62, 0.90), based on a March 3, 2014 interim OS analysis. The numbers
of patients experiencing any grade 3 or 4 adverse event were similar
in each group. The most frequent grade 3 or 4 adverse events were
neutropenia, anaemia and infections.
MM-0155 was a multi-centre, randomised, double-blind,
placebo-controlled phase III study of 459 patients that compared
melphalan-prednisone-lenalidomide induction followed by lenalidomide
maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or
melphalan-prednisone (MP) followed by placebo in patients ≥65 years or
older with newly diagnosed multiple myeloma. Progression-free survival
(PFS; study primary endpoint) was significantly improved in patients
treated with MPR-R when compared with MPR and MP (p < 0.001 for
comparisons of MPR-R over MPR and MP). In the MM-015 study, overall
survival was not significantly improved when compared across any
treatment arm. During induction, the most frequent adverse events were
hematologic (including neutropenia, thrombocytopenia, and anaemia).
During the maintenance phase, the incidence of new or worsened grade 3
or 4 adverse events was low (0 to 6%).
The EC decision for the use of REVLIMID in newly diagnosed multiple
myeloma in adult patients ineligible for transplantation follows the
positive opinion issued by the Committee for Medicinal Products for
Human Use (CHMP) in December 2014. It is the second European Commission
approval Celgene has received this year, following the approval of OTEZLA®,
the first phosphodiesterase-4 (PDE-4) inhibitor for use in psoriasis and
psoriatic arthritis, in January 2015. A CHMP positive opinion was also
issued in January for use of the company's oncology drug ABRAXANE®,
in non-small cell lung cancer.
Celgene announced on 18 February 2015 that the U.S. Food and Drug
Administration (FDA) has expanded the existing indication for REVLIMID
(lenalidomide) in combination with dexamethasone to include patients
newly diagnosed with multiple myeloma in the U.S.
In the United States, REVLIMID is approved in combination with
dexamethasone for the treatment of patients with multiple myeloma. In
the European Union, REVLIMID is approved for the treatment of adult
patients with previously untreated multiple myeloma who are not eligible
for transplant. 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 70 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, Switzerland,
Australia, New Zealand and several Latin American countries, as well as
Malaysia and Israel, for transfusion-dependent anaemia due to low- or
intermediate-1-risk MDS associated with a deletion 5q cytogenetic
abnormality with or without additional cytogenetic abnormalities and in
Europe for the treatment of patients with transfusion-dependent anemia
due to low- or intermediate-1-risk myelodysplastic syndromes associated
with an isolated deletion 5q cytogenetic abnormality when other
therapeutic options are insufficient or inadequate.
In addition, REVLIMID is approved in the United States for the treatment
of patients with mantle cell lymphoma (MCL) whose disease has relapsed
or progressed after two prior therapies, one of which included
bortezomib. In Switzerland, REVLIMID is indicated for the treatment of
patients with relapsed or refractory MCL after prior therapy that
included bortezomib and chemotherapy/rituximab.
Celgene International Sàrl, located in Boudry, in the Canton
of Neuchâtel, Switzerland, is a wholly-owned subsidiary and
International Headquarters of Celgene Corporation. 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.
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ADDITIONAL IMPORTANT SAFETY INFORMATION based on EU SmPC
REVLIMID® (lenalidomide) is contraindicated in patients with
known hypersensitivity to the active substance or to any of the
excipients in the formulation.
REVLIMID® (lenalidomide) is contraindicated during pregnancy,
and also in women of childbearing potential unless all of the conditions
of the Pregnancy Prevention Programme are met.
Warnings and precautions
Pregnancy: the conditions of the Pregnancy Prevention Programme must be
fulfilled for all patients unless there is reliable evidence that the
patient does not have childbearing potential.
Cardiovascular disorders: patients with known risk factors for
myocardial infarction or thromboembolism should be closely monitored.
Neutropenia and thrombocytopenia: complete blood cell counts should be
performed every week for the first 8 weeks of treatment and monthly
thereafter to monitor for cytopenias. A dose reduction may be required.
Infection with or without neutropenia: all patients should be advised to
seek medical attention promptly at the first sign of infection.
Renal impairment: monitoring of renal function is advised in patients
with renal impairment.
Thyroid disorders: optimal control of co-morbid conditions influencing
thyroid function is recommended before start of treatment. Baseline and
ongoing monitoring of thyroid function is recommended.
Tumour lysis syndrome: patients with high tumour burden prior to
treatment should be monitored closely and appropriate precautions taken.
Allergic reactions: patients who had previous allergic reactions while
treated with thalidomide should be monitored closely.
Severe skin reactions: REVLIMID® (lenalidomide) must be
discontinued for exfoliative or bullous rash, or if SJS or TEN is
suspected, and should not be resumed following discontinuation for these
reactions. Interruption or discontinuation of lenalidomide should be
considered for other forms of skin reaction depending on
severity. Patients with a history of severe rash associated with
thalidomide treatment should not receive lenalidomide.
Lactose intolerance: patients with rare hereditary problems of galactose
intolerance, lapp lactase deficiency or glucose-galactose malabsorption
should not take this medicinal product.
Second primary malignancies (SPM): the risk of occurrence of hematologic
SPM must be taken into account before initiating treatment with REVLIMID®
(lenalidomide) either in combination with melphalan or immediately
following high-dose melphalan and autologous stem cell transplant
(ASCT). Physicians should carefully evaluate patients before and during
treatment using standard cancer screening for occurrence of SPM and
institute treatment as indicated.
Hepatic disorders: dose adjustments should be made in patients with
renal impairment. Monitoring of liver function is recommended,
particularly when there is a history of or concurrent viral liver
infection or when REVLIMID® (lenalidomide) is combined with
medicinal products known to be associated with liver dysfunction.
Newly diagnosed multiple myeloma patients: patients should be carefully
assessed for their ability to tolerate REVLIMID®
(lenalidomide) in combination, with consideration to age, ISS stage III,
ECOG PS≤2 or CLcr < 60 mL/min.
Cataract: regular monitoring of visual ability is recommended.
Summary of the safety profile in multiple myleloma
Newly diagnosed multiple myeloma in patients treated with REVLIMID®
(lenalidomide) in combination with low dose dexamethasone:
The serious adverse reactions observed more frequently (≥5%) with
REVLIMID® (lenalidomide) in combination with low dose
dexamethasone (Rd and Rd18) than with melphalan, prednisone and
thalidomide (MPT) were pneumonia (9.8%) and renal failure (including
The adverse reactions observed more frequently with Rd or Rd18 than
MPT were: diarrhoea (45.5%), fatigue (32.8%), back pain (32.0%),
asthenia (28.2%), insomnia (27.6%), rash (24.3%), decreased appetite
(23.1%), cough (22.7%), pyrexia (21.4%), and muscle spasms (20.5%).
Newly diagnosed multiple myeloma patients treated with REVLIMID®
(lenalidomide) in combination with melphalan and prednisone:
The serious adverse reactions observed more frequently (≥5%) with
melphalan prednisone, and REVLIMID® (lenalidomide) followed
by REVLIMID® (lenalidomide) maintenance (MPR+R) or
melphalan prednisone, and REVLIMID® (lenalidomide) followed
by placebo (MPR+p) than melphalan, prednisone and placebo followed by
placebo (MPp+p) were febrile neutropenia (6.0%) and anaemia (5.3%)
The adverse reactions observed more frequently with MPR+R or MPR+ p
than MPp+p were: neutropenia (83.3%), anaemia (70.7%),
thrombocytopenia (70.0%), leukopenia (38.8%), constipation (34.0%),
diarrhoea (33.3%), rash (28.9%), pyrexia (27.0%), peripheral oedema
(25.0%), cough (24.0%), decreased appetite (23.7%), and asthenia
Patients with multiple myeloma who have received at least one prior
The most serious adverse reactions observed more frequently with
REVLIMID® (lenalidomide) and dexamethasone than with
placebo and dexamethasone in combination were venous thromboembolism
(deep vein thrombosis, pulmonary embolism) and grade 4 neutropenia
The observed adverse reactions which occurred more frequently with
REVLIMID® (lenalidomide) and dexamethasone than placebo and
dexamethasone in pooled multiple myeloma clinical trials (MM-009 and
MM-010) were fatigue (43.9%), neutropenia (42.2%), constipation
(40.5%), diarrhoea (38.5%), muscle cramp (33.4%), anaemia (31.4%),
thrombocytopenia (21.5%), and rash (21.2%).
Paediatric population: REVLIMID® (lenalidomide) should not be
used in children and adolescents from birth to less than 18 years.
Older people with newly diagnosed multiple myeloma: for patients older
than 75 years of age treated with REVLIMID® (lenalidomide) in
combination with dexamethasone, the starting dose of dexamethasone is
20 mg/day on Days 1, 8, 15 and 22 of each 28-day treatment cycle. No
dose adjustment is proposed for patients older than 75 years who are
treated with REVLIMID® (lenalidomide) in combination with
melphalan and prednisone.
Older people with multiple myeloma who have received at least one prior
therapy: care should be taken in dose selection and it would be prudent
to monitor renal function.
Patients with renal impairment: care should be taken in dose selection
and monitoring of renal function is advised. No dose adjustments are
required for patients with mild renal impairment and multiple myeloma.
Dose adjustments are recommended at the start of therapy and throughout
treatment for patients with moderate or severe impaired renal function
or end stage renal disease.
Patients with hepatic impairment: REVLIMID® (lenalidomide)
has not formally been studied in patients with impaired hepatic function
and there are no specific dose recommendations.
Please refer to the Summary of Product Characteristics for full
European prescribing information.
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 Celgene
Corporation's Annual Report on Form 10-K and other reports filed with
the Securities and Exchange Commission.
All registered trademarks are owned by Celgene Corporation.
# # #
1. Palumbo A & Anderson K. Multiple myeloma. N Engl J Med
2. Ferlay J et al. Cancer incidence and mortality patterns in Europe:
Estimates for 40 countries in 2012. Eur J Cancer 2013;49:1374-1403.
3. National Cancer Institute. SEER Stat Fact Sheets: Myeloma. http://seer.cancer.gov/statfacts/html/mulmy.html
4. Jagannath S. Treatment of myeloma in patients not eligible for
transplantation. Curr Treat Options Oncol 2005;6(3):241-53.
5. Summary of Product Characteristics, REVLIMID, February 2015.
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