lundi 30 mars 2020


U.S. FDA Grants Priority Review for Fedratinib New Drug Application in Myelofibrosis

Par Rédaction , dans Communiqués , le 5 mars 2019

Tuesday, March 5th 2019 at 12:30pm UTC

U.S. Food & Drug Administration sets Prescription Drug User Fee Act
action date for Sept. 3, 2019

SUMMIT, N.J.–(BUSINESS WIRE)– Celgene Corporation (NASDAQ:CELG) today announced the U.S. Food and Drug
Administration (FDA) has accepted the company’s New Drug Application
(NDA) for fedratinib and granted a Priority Review. Fedratinib is a
highly selective JAK2 inhibitor intended for the treatment of patients
with myelofibrosis, a serious bone marrow disorder that disrupts the
body’s normal production of blood cells.1 Under the
Prescription Drug User Fee Act, the FDA has set its action date as Sept.
3, 2019.

“The acceptance of the NDA and granting of Priority Review for
fedratinib represent the first potential new treatment option after many
years for patients affected by myelofibrosis.” said Jay Backstrom, M.D.,
Chief Medical Officer for Celgene. “Patients with myelofibrosis,
including the number who are ineligible for or failed existing therapy
continues to increase, representing a well-defined unmet medical need.
We believe fedratinib can play an important role in the treatment of
myelofibrosis and we look forward to working with the FDA as the review
process advances.”

The NDA for fedratinib is based on results from a randomized,
placebo-controlled, phase 3 trial (JAKARTA) in patients with
primary or secondary myelofibrosis, as well as a single-arm, open-label
phase 2 trial (JAKARTA2) in patients with primary or secondary
myelofibrosis previously exposed to ruxolitinib, the only FDA-approved
treatment for the disease. Results of these two trials have been
previously published in peer-reviewed journals. The FDA has also
provided fedratinib Orphan Drug designation for the treatment of
secondary and primary myelofibrosis.

Celgene also plans to evaluate fedratinib in combination with
luspatercept.

Fedratinib is an investigational compound that is not approved for any
use in any country.

About JAKARTA

JAKARTA is a pivotal phase 3, multicenter, randomized, double-blind,
placebo-controlled trial evaluating the efficacy of daily oral doses
(400 mg or 500 mg) of fedratinib compared with placebo in patients with
intermediate-2 or high-risk primary myelofibrosis, post-polycythemia
vera myelofibrosis or post-essential thrombocythemia myelofibrosis with
splenomegaly. The study included 289 subjects across 94 sites in 24
countries.

The primary endpoint was spleen response rate, defined as the proportion
of patients who had a reduction in spleen volume of at least 35% after
six one-month treatment cycles with a magnetic resonance imaging (MRI)
or computerized tomography (CT) scan four weeks later. Secondary
endpoints included symptom response rate, defined as the proportion of
patients with a 50% or greater reduction in Total Symptom Score after
six one-month treatment cycles as measured by the modified Myelofibrosis
Symptoms Assessment Form (MFSAF) v2.0 diary.

About JAKARTA2

JAKARTA2 is a phase 2, multicenter, open label, single-arm trial
evaluating the efficacy of a once daily dose of fedratinib (400 mg
starting dose) in patients previously treated with ruxolitinib and with
a diagnosis of intermediate-1 with symptoms, intermediate-2 or high-risk
primary myelofibrosis, post-polycythemia vera myelofibrosis or
post-essential thrombocythemia myelofibrosis. The study included 97
subjects across 40 sites in 10 countries.

The primary endpoint was spleen response rate, defined as the proportion
of patients who had a reduction in spleen volume of at least 35% as
measured by MRI or CT scan after six one-month treatment cycles.
Secondary endpoints included symptom response rate, defined as the
proportion of patients with a 50% or greater reduction in Total Symptom
Score after six one-month treatment cycles as measured by the modified
Myelofibrosis Symptoms Assessment Form (MFSAF) v2.0 diary.

FDA placed a clinical hold on the fedratinib program in November 2013
after potential cases of Wernicke’s encephalopathy were reported among
subjects (approximately 1%) in clinical trials. The FDA removed the
clinical hold in August 2017.

About Fedratinib

Fedratinib is an oral kinase inhibitor with activity against wild type
and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like
tyrosine kinase 3 (FLT3). Fedratinib is a JAK2-selective inhibitor with
higher potency for JAK2 over family members JAK1, JAK3 and TYK2.
Abnormal activation of JAK2 is associated with myeloproliferative
neoplasms (MPNs), including myelofibrosis and polycythemia vera. In cell
models expressing mutationally active JAK2 or FLT3, fedratinib reduced
phosphorylation of signal transducer and activator of transcription
(STAT3/5) proteins, inhibited cell proliferation, and induced apoptotic
cell death. In mouse models of JAK2V617F-driven
myeloproliferative disease, fedratinib blocked phosphorylation of
STAT3/5, increased survival and improved disease-associated symptoms,
including reduction of white blood cells, hematocrit, splenomegaly, and
fibrosis.

About Myelofibrosis

Myelofibrosis is a serious and rare bone marrow disorder that disrupts
the body’s normal production of blood cells. Bone marrow is gradually
replaced with fibrous scar tissue, which limits the ability of the bone
marrow to make red blood cells.1 The disorder can lead to
anemia, weakness, fatigue and swelling of the spleen and liver, among
other symptoms.1 Myelofibrosis is classified as a
myeloproliferative neoplasm, a group of rare blood cancers that derive
from blood-forming stem cells.2 In the U.S. myelofibrosis
occurs in 1.5 of every 100,000 people each year.3 Both men
and women are affected and, while the disease can affect people of all
ages, the median age at diagnosis ranges from 60 to 67 years4,5

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global biopharmaceutical 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,

LinkedIn
and Facebook.

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 each
company’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 the Annual Report on Form 10-K and other reports of each
company 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; pending legal proceedings or
any future litigation 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.

1 Mayo Clinic. Myelofibrosis. Available at https://www.mayoclinic.org/diseases-conditions/myelofibrosis/symptoms-causes/syc-20355057.
Accessed January 2019.

2 Leukemia & Lymphoma Society. Myelofibrosis. Available at https://www.lls.org/myeloproliferative-neoplasms/myelofibrosis.
Accessed January 2019.

3 Leukemia & Lymphoma Society. Myelofibrosis facts. Available
at https://www.lls.org/sites/default/files/file_assets/FS14_Myelofibrosis_Fact%20Sheet_Final9.12.pdf.
Accessed January 2019.

4 Abdel-Wahab O and Levine R. Primary myelofibrosis: Updates
on Definition, Pathogenesis and Treatment. Annual Review of Medicine. 2009;60:233-245.

5 Mesa R, Niblack J, Wadleigh M, et al. The burden of fatigue
and quality of life in myeloproliferative disorders (MPDs). Cancer. 2007;109:68-76.

Contacts

Celgene Corporation
Investors:
+1-908-673-9628
ir@celgene.com
or
Media:
+1-908-673-2275
media@celgene.com

Source: Celgene Corporation

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