Novartis continues to make major strides
in advancing its pipeline, in part through
the execution of the company’s bolt-on
M&A strategy. During early January 2017,
Novartis entered into an exclusive option
agreement with Ionis Pharmaceuticals and
its affiliate Akcea Therapeutics to license
two investigational treatments expected to
significantly reduce cardiovascular risk in
patients living with elevated levels of lipoprotein Lp(a) or ApoCIII, which is a potent
regulator of triglycerides.
The antisense therapies developed by
Ionis – AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx – have the potential to lower
lipoproteins up to 90; and significantly reduce cardiovascular risk in high-risk patient
populations. The investment in biomark-er-based therapies bolsters Novartis’ cardiovascular specialty pipeline and dedication
to address unmet medical need of high-risk
The acquisition of Encore Vision, as announced during December 2016, strengthens the ophthalmology pipeline of Novartis.
Through the transaction, Novartis has added
to its pipeline a first-in-class disease-modifying topical treatment for presbyopia patients
in the field of high unmet medical need and
high prevalence, known as EV06. Presbyopia
is a common age-related loss of near distance
vision characterized by a progressive inability
to concentrate on nearby objects.
Novartis additionally during December struck an option, collaboration and license deal with Conatus Pharmaceuticals
to broaden the company’s liver portfolio to
deliver best-in-class single and combination
therapies for non-alcoholic steatohepatitis
(NASH) with advanced fibrosis and cirrhosis. This transaction allows Novartis and Conatus to jointly develop emricasan.
The investigational, first-in-class, oral,
pan-caspase inhibitor is intended for treating
non-alcoholic steatohepatitis (NASH) with
advanced fibrosis (scarring) and cirrhosis.
This collaboration has the potential to expand treatment options for people in different stages of fatty liver disease, where no
approved medicines currently exist. Novartis
has FXR agonists in clinical development
for NASH, the most advanced of which is in
a Phase 2 study and has been granted Fast
Track designation from U.S. regulators.
In another pipeline-bolstering move, Novartis in December acquired ;iarco Group,
a privately held company concentrated
on the development of novel dermatology
treatments. With the acquisition comes to
Novartis the once-daily oral H4 receptor antagonist ;PL389, which is being developed
to treat atopic dermatitis, commonly known
as eczema. ;PL389 demonstrated a clinically and statistically significant improvement
of eczema lesions, resulting in a 50 percent
reduction in EASI score versus placebo after
eight weeks of treatment with a favorable
Selexys Pharmaceuticals, a company
specializing in developing therapeutics in
certain hematologic and inflammatory dis-
orders, was purchased by Novartis during
November. Novartis exercised its right to
acquire Selexys following receipt of results of
the SUSTAIN trial, a Phase II study assessing
the use of the anti-P-selectin antibody SelG1
in the reduction of vaso-occlusive pain crises
in patients with sickle cell disease (SCD). The
acquisition complements and broadens No-
vartis’ hematology pipeline and underscores
the company’s dedication to improving care
for patients with high unmet need.
Roche has more than 18,000 employ- ees working on research and develop- ment to deliver medical innovations,
a figure higher than the overall size of most
pharma and biotech companies. The company recently launched four new medicines:
Cotellic (advanced melanoma), Alecensa
(lung cancer), Venclexta (chronic lymphocytic leukemia; jointly commercialized with
AbbVie) and Tecentriq (bladder and lung
cancer). Also, five FDA breakthrough therapy designations were granted for Roche
medicines throughout 2016.
One of Roche’s most important new products is the cancer immunotherapy Tecentriq
(atezolizumab). During May 2016, Tecentriq
became the first treatment to gain U.S. marketing clearance for individuals with previously treated advanced bladder cancer in
more than 30 years. In January 2017, Roche
announced that a second Priority Review had
been granted for Tecentriq in advanced bladder cancer as a first-line treatment option for
people not eligible for cisplatin chemotherapy. An FDA decision on the product’s marketing approval for the supplemental BLA is
expected by April 30, 2017.
A monoclonal antibody, Tecentriq is designed to target and bind to a protein called
PD-L1 (programmed death-ligand 1), which
is expressed on tumor cells and tumor-infil-trating immune cells. PD-L1 interacts with
PD-1 and B7.1, both found on the surface of
T cells, resulting in T-cell inhibition. By blocking this interaction, Tecentriq may enable
T-cell activation, restoring the cells’ ability to
effectively detect and attack tumor cells.
The multiple sclerosis drug candidate
Ocrevus (ocrelizumab) is anticipated to be
one of the biggest product launches of 2017.
The investigational, humanized monoclonal
antibody is designed to selectively target
CD20-positive B cells. That specific type
of immune cell is believed to be a key con-
tributor to myelin (nerve cell insulation and
support) and axonal (nerve cell) damage,
which can lead to disability in people with
MS. Ocrevus binds to CD20 cell surface pro-
teins expressed on certain B cells, but not
on stem cells or plasma cells, and therefore
significant functions of the immune system
may be preserved.
Ocrevus is the first investigational medicine to demonstrate superior efficacy versus
comparators in relapsing and primary progressive multiple sclerosis in clinical trials.
The product showed a favorable safety profile in three large Phase III trials. Ocrevus is
the first investigational medicine to significantly reduce the progression of physical
disability in primary progressive MS in a
large Phase III study. Data from Phase III
trials demonstrated consistent and clinically
meaningful reductions in major markers of
disease activity and progression compared
with Rebif (interferon beta-1a) in RMS and
with placebo in PPMS.
Marketing applications for Ocrevus,
filed for RMS and PPMS, have been validat-ed and are under review by the European
Medicines Agency (EMA) and U.S. Food
and Drug Administration. The Prescription
Drug User Fee Act (PDUFA) date for the approval review of the Biologics License Application (BLA) of Ocrevus is March 28, 2017.
Assuming an FDA green light on this date,
Ocrevus global sales are expected to top $4
billion by 2022 per industry analysts.
Another anticipated future blockbuster
emerging from the Roche pipeline is the
investigational bispecific monoclonal antibody emicizumab. Also known by the product code ACE910, emicizumab is designed
to bring together factors I;a and ;. The
two proteins are necessary to activate the
natural coagulation cascade and restore the
blood-clotting process. The drug compound
can be administered by an injection of a
ready-to-use solution under the skin (
subcutaneously) once every week.
Emicizumab is being studied in pivotal
phase III trials in people 12 years of age and
older, with and without inhibitors to factor
VIII, and in children younger than 12 years
old with factor VIII inhibitors. Future stud-
ies will seek to assess less frequent dosing
schedules. The development program is
evaluating emicizumab’s potential to help
overcome current clinical challenges, in-
cluding the short-lasting effects of existing
treatments, the development of factor VIII
inhibitors and the necessity for frequent ve-
nous access. Emicizumab was discovered by
Chugai Pharmaceutical Co. Ltd. and is being
jointly developed in conjunction with Roche
by Chugai and Genentech.
In December 2016, Roche reported that
the potential hemophilia A treatment met
its primary endpoint as well secondary ones
in the first pivotal phase III trial, known as
Haven 1. Emicizumab prophylaxis reduced
the amount of bleeds over time versus no
prophylaxis in people with hemophilia A
and inhibitors to factor VIII. HAVEN 1 is
a randomized, multicenter, open-label trial
assessing the efficacy, safety, and pharma-cokinetics of emicizumab.
Roche presented other significant clinical results during 2016. A pivotal study in a
group of people with hemophilia A (Haven
1) demonstrated that prophylaxis with emicizumab resulted in a significant reduction
in the number of bleeds over time. A phase
III trial by Roche company Chugai (J-Alex)
found that first-line treatment with Alecensa significantly reduced the risk of disease
worsening or death compared to crizotinib,
the current standard of care, for individuals
with ALK-positive NSCLC. Gazyva;Gazyvaro
demonstrated positive results in a major clinical study (Gallium) in follicular lymphoma.
Additionally in 2016, Roche presented
data from the largest clinical study performed to date in giant cell arteritis (GCA),
a serious inflammatory disease of blood vessels. Initially combined with a steroid regimen, Actemra;RoActemra more effectively
sustained remission versus a steroid-only
regimen in patients with newly diagnosed
and relapsing GCA.
As of the beginning of February 2017, Sanofi’s R;D pipeline consisted of 44 pharmaceutical new molecular
entities (excluding Life Cycle Management)
and vaccine candidates in clinical development. Of that total, 13 were in Phase III or
had been filed with regulatory authorities
for marketing clearance. According to the
company, more than 50 percent of projects
stem from collaborations and partnerships.
Within Sanofi’s R;D portfolio, industry
analysts as a consensus are most excited
about the dermatology drug Dupixent (
dup-ilumab). The product is intended for the
treatment of adults with moderate-to-se-vere atopic dermatitis (AD) who are candidates for systemic therapy. The investigational biologic therapy inhibits signaling
of IL- 4 and IL- 13, two key cytokines necessary for the type 2 (including Th2) immune
response, which is believed to be a major
driver in the pathogenesis of the disease.
A biologics license application (BLA) for
Dupixent was accepted for Priority Review
by the U.S. Food and Drug Administration
during September 2016. Per the Prescription Drug User Fee Act (PDUFA), the target
FDA action date is set for March 29, 2017.
During December 2016, Sanofi and Regeneron Pharmaceuticals Inc. announced that
the European Medicines Agency (EMA) had
accepted for review the Marketing Authorization Application (MAA) for Dupixent.
In addition to atopic dermatitis in adults,
Dupixent is undergoing clinical studies in
pediatric AD, asthma, nasal polyposis and
eosinophilic esophagitis. If cleared for marketing, Dupixent would be commercialized
by Regeneron and Sanofi Genzyme, the specialty care global business unit of Sanofi.
2017 an important year for our pipeline
Q1 Q2 Q3 Q4
(Tecentriq 1L Lung)
(Perjeta aBC, Her2+)