duction in the risk of death or permanent
ventilation in Spinraza-treated infants with
SMA compared to untreated infants.
Two months earlier, Biogen and Ionis
Pharmaceuticals announced that Spinraza
met the primary endpoint at the interim
analysis of CHERISH, a Phase III trial assessing the drug in later-onset (consistent
with Type 2) SMA. The analysis found that
children receiving Spinraza experienced a
highly statistically significant improvement
in motor function versus those who did not
receive treatment. The new medicine additionally displayed a favorable benefit-risk
profile in the clinical study.
Biogen’s aducanumab is being tested in
two worldwide Phase III trials, ENGAGE
and EMERGE. The two studies are designed
to assess the drug compound’s safety and
efficacy in slowing cognitive impairment
and the progression of disability in people
with early Alzheimer’s disease. A human
recombinant monoclonal antibody (mAb),
aducanumab is derived from a de-identi-fied library of B cells collected from healthy
elderly subjects with no signs of cognitive
impairment or cognitively impaired elderly
subjects with unusually slow cognitive decline using Neurimmune’s technology platform called Reverse Translational Medicine
(RTM). Biogen licensed aducanumab from
Neurimmune through a collaborative development and license deal. Aducanumab is
believed to target aggregated forms of beta
amyloid including soluble oligomers and
insoluble fibrils that can form into amyloid
plaque in the brain of AD patients. Based
on pre-clinical and Phase Ib data, treatment
with aducanumab has been demonstrated
to reduce amyloid plaque levels.
During August 2016, aducanumab was
accepted into the EMA’s PRIME program.
During the following month, the FDA accepted aducanumab – also known by the product
code BIIB037 – into its Fast Track program.
Industry analysts have high hopes for aducanumab, which has been rated by EvaluatePharma as one of the top 20 most valuable
R&D projects per an August 2016 report. The
new drug candidate ranked No. 8 in that report with a net present value of $6.89 billion.
Siemens Healthineers and Biogen are
jointly developing magnetic resonance imaging (MRI) applications with the intent of
quantifying key markers of multiple sclerosis (MS) disease activity and progression,
per a deal struck in January 2017.
Other key pipeline events for Biogen
during 2017 include full enrollment of Phase
IIb for natalizumab in stroke; Phase IIb
initiation for opicinumab in MS; potential
BAN2401 data in Alzheimer’s; and Phase II
completion for BG00011 in idiopathic pul-
Natalizumab targets key mediators of
post-ischemic inflammation and neuro-
toxicity. In a Phase II ACTION trial, natal-
izumab did not reduce MRI-defined infarct
volume, but demonstrated benefit on key
clinical measures up to 9 hours after onset.
A second dose-ranging Phase II trial (AC-
TION 2) with an extended time window is
scheduled to be fully enrolled during 2017.
Opicinumab (anti-LINGO-1) is an investigational, fully human monoclonal antibody being developed as a potential neu-roreparative therapy for individuals with
relapsing forms of multiple sclerosis (RMS).
Two Phase II studies (RENEW and SYNERGY) were designed to test the biological
activity and clinical potential of opicinumab
in CNS demyelinating diseases.
Summit, N.J.-based Celgene is an in- tegrated global biopharma company engagedmainlyinthediscovery, devel-
opment and commercialization of innovative
therapies for treating cancer and inflammato-
ry diseases through next-generation solutions
in protein homeostasis, immuno-oncology,
epigenetics, immunology and neuro-inflam-
mation. Management says the company is
developing innovative therapies that address
the source of disease, not just the symptoms.
Celgene’s discovery and development plat-
forms for drug and cell-based therapies allow
the company to create and retain significant
value within its therapeutic franchise fields of
cancer and inflammatory diseases. Company
leadership says, “Scientists and physicians
at Celgene are the driving force behind our
success, enabling target-to-therapeutic plat-
forms that integrate both small-molecule and
According to its executives, leading-edge
scientific research in oncology remains Cel-
gene’s passion. The company is concentrat-
ed on developing disruptive approaches to
high-value disease pathways that translate
into life-enhancing medicines with the ul-
timate goal to change the course of human
health while promising to always put pa-
Celgene has developed target-identifi-cation and drug-discovery technology platforms that allow the company to rapidly proceed from target identification and validation
through lead identification and optimization.
Celgene’s full-year 2016 R&D expendi-
ture totaled $4.47 billion compared to $3.7
billion during 2015.
“In 2016, we made exceptional progress
strengthening and growing our franchises
while accelerating and adding to our robust
pipeline; our significant business momentum
supports raising our 2017 guidance,” noted
Mark J. Alles, CEO of Celgene. “We are entering a pivotal two-year period with multiple catalysts increasing our confidence in our
ability to achieve or exceed our 2020 targets
and sustain our growth from 2020 to 2030.”
The Phase III product candidate ozanimod is considered by various health analysts
as one of the industry’s most valuable R&D
projects. The novel, oral, selective sphingosine
1-phosphate 1 and 5 receptor modulator is
undergoing development for immune-in-flammatory indications including inflammatory bowel disease and relapsing multiple
sclerosis. Treatment with S1P receptor modulators is thought to work by interfering with
S1P signaling and preventing a certain subtype (ccr7+) of lymphocytes (a type of white
blood cell) from exiting the lymph nodes and
contributing to tissue inflammation.
TOUCHSTONE is a Phase II, randomized, double-blind, placebo-controlled study
comparing the efficacy and safety of ozanimod (additionally known as RPC1063) with
placebo in patients with moderate to severe
active ulcerative colitis. TOUCHSTONE
met its primary endpoint and secondary
endpoints with statistical significance for
patients on the 1-milligram dosage of ozanimod compared to placebo.
The phase III TRUE NORTH registration
trial with ozanimod in patients with ulcerative colitis is enrolling with data expected
during 2018. Data from a proof of concept
phase II study of ozanimod in patients with
Crohn’s disease are anticipated during 2017.
Celgene is anticipating making important
progress with various operational milestones
during 2017. In the hematology/oncology
area, FDA approval is expected for enasidenib
(AG-221) as a treatment for patients with relapsed and/or refractory acute myeloid leukemia (AML) with isocitrate dehydrogenase-2
(IDH2) mutation. Enrollment is expected to
begin in a pivotal program with JCAR017 in
relapsed and/or refractory non-Hodgkin’s
lymphoma in collaboration with Juno Therapeutics. In the Inflammation and Immunology (I&I) category, the company is on track
with the U.S. submission of an NDA for ozanimod in patients with multiple sclerosis and
an FDA filing for a supplemental NDA for the
Otezla once-daily formulation.
The investigational drug JCAR017 during
December 2016 was granted breakthrough
therapy designation by U.S. regulators for
treating patients with relapsed/refractory
(r/r) aggressive large B-cell non-Hodgkin
lymphoma, including diffuse large B-cell
lymphoma (DLBCL), not otherwise specified
(de novo or transformed from indolent lym-
phoma), Primary mediastinal B-cell lympho-
ma (PMBCL) or Grade 3B follicular lympho-
ma. Also, the EMA Committee for Medicinal
Products for Human Use (CHMP) and Com-
mittee for Advanced Therapies (CAT) grant-
ed JCAR017 access to the priority medicines
(PRIME) scheme for r/r DLBCL.
Celgene says JCAR017 uses a defined
CD4:CD8 cell composition and 4-1BB as the
costimulatory domain, which differentiates
it from other CD19-directed CAR T product
candidates undergoing clinical development. Juno Therapeutics is building a fully
integrated biopharma company concentrated on re-engaging the body’s immune
system to revolutionize oncology treatment.
Plans are under way to initiate a pivotal U.S.
study in patients with relapsed or refractory
DLBCL during 2017. If approved for marketing, JCAR017 is expected to attain blockbuster sales status.
Speaking of blockbusters, Otezla (
apremi-last) is the first in a new class of medicines
approved for treating psoriasis and psoriatic
arthritis, two diseases involving dysregulated
immune system activity. The drug is an oral
small-molecule inhibitor of phosphodiester-ase 4 (PDE4) specific for cyclic adenosine
monophosphate (cAMP). PDE4 inhibition
results in increased intracellular cAMP levels
which is thought to indirectly modulate the
production of inflammatory mediators. As
of December 2016, Otezla had been cleared
for marketing in 37 countries, including the
United States, Europe and Japan. Since
FDA’s 2014 approval of Otezla, Celgene has
continued to develop novel orally available
small molecules that inhibit the production
of multiple pro-inflammatory mediators.
Those small molecules include interleukin-2
(IL-2), IL- 12, interferon-gamma, TNF-alpha,
leukotrienes and nitric oxide synthase.
Celgene’s lead investigational product,
GED-0301, is an oligonucleotide that targets
the messenger RNA for Smad7. In patients
with Crohn’s disease, abnormally high levels of
Smad7 interfere with TGF-;1 anti-inflamma-
tory pathways in the gut, resulting in increased
inflammation. Also known as mongersen,
GED-0301 is designed to work locally to re-
duce Smad7 levels with negligible systemic
exposure. The drug candidate is undergoing
Phase III clinical studies for Crohn’s disease
and Phase II trials for ulcerative colitis. If its
present development path proceeds on course,