- Oral REVLIMID® is the
first and only medicine licensed in Europe for use as
post-autologous stem cell transplantation maintenance therapy in
multiple myeloma
- The new indication expands the
availability of REVLIMID® across the disease
continuum of multiple myeloma
Celgene International Sàrl, a wholly-owned subsidiary of Celgene
Corporation (NASDAQ: CELG), today announced that the European
Commission (EC) has approved REVLIMID® (lenalidomide) as
monotherapy for the maintenance treatment of adult patients with
newly diagnosed multiple myeloma who have undergone autologous stem
cell transplantation (ASCT). REVLIMID® is the first and only
licensed maintenance treatment available to these patients.
The REVLIMID® Marketing Authorisation has been updated to
include this new indication, which expands on the existing multiple
myeloma indications as combination therapy for the treatment of
those not eligible for transplant who are newly diagnosed, or have
received at least one prior therapy.
Multiple myeloma is an incurable 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 39,000 people are diagnosed with multiple myeloma in Europe,
and around 24,000 people die from the disease each year.2 The
median age at diagnosis in Europe is between 65 and 70 years.3 In
Europe, patients who are fit and in good clinical condition are
typically considered eligible for ASCT.4
For patients who are newly diagnosed with multiple myeloma and
eligible for ASCT, key treatment goals are to delay disease
progression and ultimately achieve long-term control over multiple
myeloma.5 These patients typically receive induction therapy and
high-dose chemotherapy with melphalan followed by ASCT. This
treatment approach has been an established standard of care for
over 20 years.6 Considering that over half of those patients who
relapse do so within 2 to 3 years of ASCT,7,8 the approval of a
maintenance therapy for use after ASCT that may delay disease
progression represents a major advance for these patients.
“After ASCT, most patients will still see their disease recur or
progress. We now have an opportunity to enhance immune function and
delay disease progression by controlling residual malignant cells
and slowing tumour growth. REVLIMID® has been shown to increase
progression-free survival after ASCT in clinical trials. Having a
licensed therapy for use in this very important setting means we
now have the opportunity to delay disease progression by sustaining
the response,” says Professor Michel Attal, Executive Director of
the Institut Universitaire du Cancer Toulouse Oncopole and Institut
Claudius Regaud, France.
The EC decision to approve REVLIMID® as monotherapy for multiple
myeloma in the post-ASCT setting was based on the results of two
cooperative group-led studies, CALGB 1001049 and IFM 2005-02.10
- CALGB
100104 was a phase III, controlled, double-blind,
multi-centre study of 460 patients with newly diagnosed multiple
myeloma undergoing ASCT who were randomized to receive continuous
daily treatment with REVLIMID® or placebo until relapse or
intolerance.
- IFM
2005-02 was an international, phase III, controlled,
double-blind, multi-centre study of 614 patients newly diagnosed
with multiple myeloma who were randomized to receive a 2-month
consolidation regimen post-ASCT of REVLIMID® monotherapy, followed
by continuous daily treatment with either REVLIMID® or placebo
until relapse or intolerance.
In both studies, the primary efficacy endpoint in the study was
progression-free survival (PFS) from transplant to the date of
disease progression or death, whichever occurred first. REVLIMID®
monotherapy as maintenance treatment post-ASCT significantly
reduced the risk of disease progression or death in patients with
multiple myeloma, leading to the studies being unblinded based on
passing their pre-specified boundary for superiority at interim
analysis. The updated PFS, using a cut-off of 1 February 2016
continues to show a PFS advantage:
- CALGB
100104: after 81.6 months of follow up, median PFS was 56.9
months (95% CI 41.9, 71.7) in the REVLIMID® arm versus 29.4 months
(95% CI 20.7, 35.5) in the placebo arm (HR=0.61; 95% CI 0.48, 0.76;
p<0.001).
- IFM
2005-02: after 96.7 months of follow up, median PFS was 44.4
months (95% CI 39.6, 52.0) in the REVLIMID® arm versus 23.8 months
(95% CI 21.2, 27.3) in the placebo arm (HR=0.57; 95% CI 0.47, 0.68;
p<0.001).
Individual studies were not powered for an overall survival (OS)
endpoint. Using a cut-off of 1 February 2016, a descriptive
analysis showed that the median overall survival in the CALGB
100104 was 111.0 months (95% CI, 101.8, not estimable) for patients
who received REVLIMID versus 84.2 (95% CI 71.0, 102.7) in the
placebo arm (HR=0.61; 95% CI 0.46, 0.81; p<0.001). In the IFM
2005-02 study, median overall survival was 105.9 months (95% CI,
88.8, not estimable) for patients who received REVLIMID versus 88.1
(95% CI 80.7, 108.4) in the placebo arm (HR=0.90; 95% CI 0.72,
1.13; p=0.355, not significant).
In both of these phase III studies, the safety profile was in
line with other clinical data in newly diagnosed non-stem cell
transplant and a post-approval safety study in relapsed/refractory
multiple myeloma. The most commonly reported adverse events in
these two studies were haematological, and included neutropenia and
thrombocytopenia. The most commonly reported non-haematological
adverse events were infections. An increased incidence rate of
haematological second primary malignancies (SPMs) was also observed
in the REVLIMID® group compared with the placebo group in both
studies. However, the EC decision confirms that the benefit-risk
ratio for REVLIMID® is positive in this expanded indication.
Tuomo Pätsi, President of Celgene European and International
Operations, said, “We are glad to provide a treatment option for
these patients with multiple myeloma, who have previously had no
licensed medicine available to them for maintenance treatment
following ASCT. This latest approval underlines the important role
of REVLIMID® in the treatment of multiple myeloma, extending its
use across the disease spectrum, and demonstrating our commitment
to multiple myeloma patients. We continue to invest in research and
development as we strive to turn multiple myeloma – and other
currently incurable diseases – into manageable conditions.”
The EC decision for the use of REVLIMID® as monotherapy for the
maintenance treatment of adult patients with newly diagnosed
multiple myeloma who have undergone ASCT follows the positive
opinion issued by the Committee for Medicinal Products for Human
Use (CHMP) in January 2017.
Celgene announced on 22 February 2017 that the U.S. Food and
Drug Administration (FDA) has expanded the existing indication for
REVLIMID® to include use for patients with multiple myeloma as
maintenance therapy following autologous hematopoietic stem cell
transplant in the U.S.
About CALGB 100104
CALGB 100104 was a phase III, randomised, controlled,
double-blind, multi-centre study conducted in 47 centres in the
United States. A total of 460 patients newly diagnosed with
multiple myeloma – aged between 18 and 70 years – who achieved at
least stable disease or better 100 days after undergoing autologous
stem cell transplant, were randomised to receive either REVLIMID®
maintenance (10 mg/day for 3 months, then 15 mg/day) or placebo,
until disease progression, intolerable side effects or death.
About IFM 2005-02
IFM 2005-02 was a phase III, controlled, double-blind,
multi-centre study conducted in 77 centres across 3 countries in
Europe. A total of 614 patients newly diagnosed with multiple
myeloma, who were younger than 65 years without signs of disease
progression within 6 months of undergoing autologous stem cell
transplant, were then randomised to receive a 2-month consolidation
regimen of REVLIMID® monotherapy, 25 mg per day on 21/28 days,
followed by either REVLIMID® maintenance (10 mg/day for 3 months,
then 15 mg/day) or placebo, until disease progression, intolerable
side effects or death.
About REVLIMID®
REVLIMID® as combination therapy is approved in Europe, in the
United States, in Japan and in around 25 other countries for the
treatment of adult patients with previously untreated multiple
myeloma (MM) who are not eligible for transplant. REVLIMID® is also
approved in combination with dexamethasone for the treatment of
patients with MM 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
myelodysplastic syndromes (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 MDS
associated with an isolated deletion 5q cytogenetic abnormality
when other therapeutic options are insufficient or inadequate.
In addition, REVLIMID® is approved in Europe and 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.
REVLIMID is not indicated and is not recommended for the
treatment of patients with chronic lymphocytic leukemia (CLL)
outside of controlled clinical trials.
ADDITIONAL IMPORTANT SAFETY INFORMATION based on EU
SmPC
Contraindications
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 myeloma
Newly diagnosed multiple myeloma: patients who have undergone
ASCT treated with REVLIMID® (lenalidomide) maintenance:
- The serious adverse reactions observed
more frequently (≥5%) with REVLIMID® (lenalidomide) maintenance
than placebo were pneumonias (10.6%) and lung infection (9.4%)
- The adverse reactions observed more
frequently with REVLIMID® (lenalidomide) maintenance than placebo
were neutropenia (79.0%), thrombocytopenia (72.3%), diarrhoea
(54.5%), bronchitis (47.4%), nasopharyngitis (34.8%), muscle spasms
(33.4%), leucopenia (31.7%), rash (31.7%), asthenia (29.7%), cough
(27.3%), upper respiratory tract infection (26.8%), fatigue
(22.8%), gastroenteritis (22.5%), anaemia (21.0%), and pyrexia
(20.5%).
Newly diagnosed multiple myeloma: patients who are not eligible
for transplant 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 acute) (6.3%).
- 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 who are not eligible
for ASCT 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 (22.0%).
Patients with multiple myeloma who have received at least one
prior therapy:
- 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%).
Special populations
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.
ABOUT CELGENE
Celgene International Sàrl, located in Boudry, 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 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: @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 Celgene’s
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’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, et al. N Engl J Med. 2011;364:1046–1060.
2 Ferlay J, et al. Eur J Cancer. 2013;49:1374–1403
3 Moreau P, et al. Ann Oncol. 2013; 24 (Suppl 6):
vi133-vi137
4 Moreau P, et al. Ann Oncol. 2013; 24 (Suppl 6):
vi133-vi137
5 Stewart AK, et al. Blood. 2009;114:5436-5443.
6 Bird JM, et al. Br J Haematol. 2011;154:32-75
7 Attal M, et al. Blood. 2006 Nov 15;108(10):3289-94
8 Child JA, et al. N Engl J Med. 2003; 348:1875-1883
9 McCarthy PL, et al. N Engl J Med. 2012;366(19):1770-1781.
CALGB is the cooperative group Cancer and Leukemia Group B (now
known as Alliance).
10 Attal M, et al. N Engl J Med. 2012;366(19):1782-1791. IFM is
the cooperative group Intergroupe Francophone du Myélome.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170224005278/en/
Media:Stacey MintonOffice: +41 32 729 62 36 / Cell: +41
79 265 23 52sminton@celgene.comorMaryline Iva+41 79 816 16
94miva@celgene.comorInvestors:+41 32 729
8303ir@celgene.com
Celgene (NASDAQ:CELG)
Historical Stock Chart
From Apr 2024 to May 2024
Celgene (NASDAQ:CELG)
Historical Stock Chart
From May 2023 to May 2024