Celgene Receives Positive CHMP Opinion to Expand REVLIMID® (Lenalidomide) Indication as Monotherapy for the Maintenance Treatment of Patients with Newly Diagnosed Multiple Myeloma (MM) after Autologous Stem Cell Transplantation

BOUDRY, Switzerland–(BUSINESS WIRE)– Celgene International Sàrl, a wholly owned subsidiary of Celgene
Corporation (NASDAQ:CELG), today announced that the European Medicines
Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has
adopted a positive opinion for the use of REVLIMID^® as
monotherapy for the maintenance treatment of adult patients with newly
diagnosed multiple myeloma (MM) who have undergone autologous stem cell
transplantation (ASCT). Once approved by the European Commission,
REVLIMID® will be the first and only licensed maintenance treatment
available to these patients.

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 MM 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 under
65 years, fit and in good clinical condition are typically considered
eligible for ASCT.⁴

For newly diagnosed, transplant-eligible MM patients, key treatment
goals are to obtain and to maintain a deep response to therapy, with the
ultimate objective of delaying disease progression.^5,6 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.⁷ Considering
that over half of patients relapse within 2 to 3 years after ASCT,^8,9
trials have been conducted to assess whether maintenance therapy
following ASCT could enable more durable remissions.

“Studies show that maintenance treatment after ASCT with REVLIMID^®
may help control residual malignant cells and delay tumour growth by
enhancing immune function,” says Professor Michel Attal, Executive
Director of the Institut Universitaire du Cancer Toulouse Oncopole
and Institut Claudius Regaud, France. “Our primary goal is to
delay disease progression for as long as possible, and we have seen in
several independent studies, that REVLIMID^®
maintenance after ASCT can halve the risk of disease progression by
sustaining the response.”

The CHMP recommendation was based on the results of two cooperative
group-led studies, CALGB 100104¹⁰ and IFM 2005-02¹¹:

• CALGB 100104 was a phase III, controlled, double-blind, multi-centre
  study of 460 patients with newly diagnosed MM undergoing ASCT who
  received continuous daily treatment with REVLIMID^® or
  placebo until relapse.
• IFM 2005-02 was an international, phase III, controlled, double-blind,
  multi-centre study of 614 patients newly diagnosed with MM 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.

In the two phase III studies, REVLIMID^® monotherapy as
maintenance treatment post-ASCT significantly reduced the risk of
disease progression or death in patients with MM, leading to the studies
being unblinded based on passing their pre-specified boundary for
superiority at interim analysis.

In these studies, the safety profile was in line with other clinical
data in newly diagnosed non-stem cell transplant (NSCT) and
post-approval safety study in relapsed/refractory MM (rrMM). Across both
phase III clinical studies, the most commonly reported adverse events
(AE) were haematological and included neutropenia and thrombocytopenia.
The most commonly reported non-haematological AE were infections. In
both trials, an increased incidence rate of haematologic second primary
malignancies (SPMs) has been observed in the REVLIMID^® group
compared with the placebo group. However, the CHMP positive opinion
confirms that the benefit-risk ratio for REVLIMID^® is
positive in this expanded indication.

Tuomo Pätsi, President of Celgene in Europe, the Middle East and Africa
(EMEA), said, “Despite substantial progress made so far in multiple
myeloma treatment, it remains an incurable disease. We welcome this CHMP
opinion as it confirms the important role that REVLIMID^®
plays in treating multiple myeloma, extending the use of REVLIMID^®
across the disease continuum. At Celgene, we aspire to turn some of the
most challenging diseases, like multiple myeloma, into manageable
conditions. Therefore, we will continue to invest more than one-third of
our revenues back into research and development.”

The CHMP reviews applications for all 28 member states in the European
Union (EU), as well as Norway, Liechtenstein and Iceland. The European
Commission, which generally follows the recommendation of the CHMP, is
expected to make its final decision in approximately two months. If
approval is granted, detailed conditions for the use of this product
will be described in the Summary of Product Characteristics (SmPC),
which will be published in the revised European Public Assessment Report
(EPAR).

About CALGB 100104

CALGB 100104 was a phase III, randomised, controlled, double-blind,
multi-centre study conducted in 47 centres in the United States. 460
newly diagnosed multiple myeloma patients – aged between 18 and 70 years
– who achieved at least stable disease (SD) or better 100 days after
undergoing autologous stem cell transplant (ASCT), 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. 614 newly
diagnosed multiple myeloma patients younger than 65 years without signs
of disease progression within 6 months of undergoing ASCT, were then
randomised to receive a two-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^® in combination with dexamethasone 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.

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 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
  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 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,
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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
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
Hoering A, et al. Blood. 2009;114:1299-1305
⁷
Bird JM, et al. Br J Haematol. 2011;154:32-75
⁸
Attal M, et al. Blood. 2006 Nov 15;108(10):3289-94
⁹
Child JA, et al. N Engl J Med. 2003; 348:1875-1883
¹⁰
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).
¹¹ Attal M, et al. N Engl J Med.
2012;366(19):1782-1791. IFM is the cooperative group Intergroupe
Francophone du Myélome.

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