48 | Novartis Annual Report 2014

innovation

Novartis Annual Report 2014 | 49

innovation | pipeline

pipeline
Novartis is consistently rated as
having one of the industrys most
respected development pipelines, with
more than 200 projects in clinical
development, including 135 in the
Pharmaceuticals Division, as of
Dec. 31, 2014.

MAJOR DEVELOPMENT PROJECTS

PHASE l PHASE ll PHASE lll

Submission

Planned
Project/product
Division
Common name
Mechanism of action
Potential indication/disease area
Route of administration filing dates1,2
Oncology
BYL719

Pharmaceuticals alpelisib

PI3K3 inhibitor

Solid tumors

Oral

2019

LJM716

Pharmaceuticals

HER3 inhibitor

Solid tumors

Intravenous

2019

EGF816

Pharmaceuticals

Epidermal growth factor receptor

Solid tumors

Oral

2019

Many of these projects, which include new

BGJ398

Pharmaceuticals

Pan-FGF receptor kinase inhibitor

Solid tumors

Oral

2019

molecular entities as well as additional indica-

INC280

Pharmaceuticals

capmatinib

cMET inhibitor

Non-small cell lung cancer

Oral

2018

tions and different formulations for marketed

Tasigna

Pharmaceuticals

nilotinib

BCR-ABL inhibitor

Chronic myeloid leukemia treatment-free remission

Oral

2016

products, are for potentially best-in-class or

LGX818

Pharmaceuticals

encorafenib

RAF inhibitor

Solid tumors

Oral

2019

first-in-class medicines that could significantly

Afinitor/Votubia
Pharmaceuticals everolimus
mTOR4 inhibitor
(RAD001)

Non-functioning GI and lung neuroendocrine tumors,

Oral
2015
tuberous sclerosis complex seizures, DLBCL5

advance treatment standards for patients

LCI699

Cushings disease

worldwide. This table provides an overview of

Pharmaceuticals

osilodrostat

Aldosterone synthase inhibitor

Oral

2017

BKM120
Pharmaceuticals buparlisib
PI3K3 inhibitor

Metastatic breast cancer, hormone receptor-positive, aromatase Oral

2015
inhibitor resistant, mTOR4 inhibitor naive [lead indication];
metastatic breast cancer, hormone receptor-positive, aromatase
inhibitor and mTOR4 inhibitor resistant solid tumors

LEE011
Pharmaceuticals ribociclib
CDK4/66 inhibitor

HR+, HER2 negative advanced breast cancer (postmenopausal

Oral
2016
women)[lead indication]; HR+, HER2 negative advanced breast
cancer (premenopausal women); solid tumors

flexible and efficient. Our development para-

MEK1627

Pharmaceuticals binimetinib

MEK8 inhibitor

NRAS mutant melanoma [lead indication], LGSOC,9 solid tumors

Oral

2016

digm consists of two parts: Exploratory

MEK162 + LGX818

Pharmaceuticals

MEK inhibitor + RAF inhibitor

RAF mutant melanoma

Oral

2016

Development and Confirmatory Development.

PKC412
Pharmaceuticals midostaurin
Signal transduction inhibitor

Exploratory development

Signifor LAR (SOM230) Pharmaceuticals pasireotide

Somatostatin analogue
Cushings disease

selected projects in confirmatory development.

We use the traditional pipeline model as a
platform (e.g. Phase I-III). However, we have
tailored the process to be simpler, more

This consists of clinical proof-of-concept studies,

which are small clinical trials that combine
elements of traditional Phase I/II testing. These
customized trials are designed to give early
insights into issues such as safety, efficacy and
toxicity for a drug in a given indication. Once a
positive proof of concept has been established,
the drug moves to the Confirmatory Development stage.
Confirmatory development
These are projects for which a positive proof
of concept has been established. They have
elements of traditional Phase II/III testing and
include trials aimed at confirming the safety
and efficacy of the drug in the given indication
leading up to submission of a dossier to
health authorities for approval. Like traditional
Phase III testing, this stage can also include
trials that compare the drug to the current
standard of care for the disease, in order to
evaluate the drugs overall risk/benefit profile.
The pipeline table provides an overview of
selected projects in Confirmatory Development. See the glossary on pages 50 and 52
for further explanation of the terms used.

binimetinib, encorafenib

Acute myeloid leukemia [lead indication],

Oral
2015
aggressive systemic mastocytosis
Long-acting release, 2016
Intramuscular
injection

Zykadia (LDK378)
Pharmaceuticals ceritinib
ALK10 inhibitor

ALK10+ advanced non-small cell lung cancer (post chemo-

Oral
US approved
therapy and post crizotinib)[lead indication], ALK10+ advanced
EU registration
non-small cell lung cancer (chemotherapy naive, crizotinib naive)

Jakavi

Polycythemia vera

Pharmaceuticals

ruxolitinib

LBH589
Pharmaceuticals panobinostat

Janus kinase inhibitor

Oral

Pan-deacetylase inhibitor
Relapsed or relapsed-and-refractory multiple myeloma
Oral
(pan-DACi)

EU registration
US registration
EU registration

Exjade
Pharmaceuticals deferasirox
Iron chelator
Iron overload
Oral FCT
US registration
film-coated tablet (FCT)

Cardiovascular and Metabolism
BGS649

Pharmaceuticals

Aromatase inhibitor

Obese hypogonadotropic hypogonadism

Oral

2019

LIK066

Pharmaceuticals

SGLT 1/2 inhibitor

Type 2 diabetes

Oral

2019

ACZ885
Pharmaceuticals canakinumab

Anti-interleukin-1
Secondary prevention of cardiovascular events
monoclonal antibody

Subcutaneous
2017
injection

LCQ908
Pharmaceuticals pradigastat

Diacylglycerol acyl
Familial chylomicronemia syndrome
Oral
2015
transferase-1 inhibitor

RLX030
Pharmaceuticals serelaxin

Recombinant form of human

Acute heart failure
Intravenous infusion 2016
relaxin-2 hormone

Tekturna
Pharmaceuticals aliskiren
Direct renin inhibitor

Reduction of cardiovascular death/hospitalizations

Oral
2016
in chronic heart failure

LCZ696
Pharmaceuticals valsartan, sacubitril
Angiotensin receptor,

(as sodium salt complex)
neprilysin inhibitor

Chronic heart failure with reduced ejection fraction

Oral
US registration
[lead indication], chronic heart failure with preserved
EU registration
ejection fraction

Respiratory
BCT197

Pharmaceuticals

Anti-inflammatory agent

QAW039
Pharmaceuticals
fevipiprant CRTH2 antagonist

Chronic obstructive pulmonary disease

Oral

Asthma

Oral 2019

2019

QAX576
Pharmaceuticals

Anti-interleukin-13
Allergic diseases
monoclonal antibody

Subcutaneous
2019
injection

QGE031
Pharmaceuticals

High-affinity anti-IgE
Asthma
monoclonal antibody

Subcutaneous
2019
injection

Seebri (NVA237)
Pharmaceuticals glycopyrronium bromide
Long-acting muscarinic antagonist
Chronic obstructive pulmonary disease
Inhalation

EU approved
US registration11

Chronic obstructive pulmonary disease

Inhalation
Long-acting beta2 adrenergic agonist
and long-acting muscarinic antagonist

EU approved
US registration11

Ultibro (QVA149)
Pharmaceuticals

indacaterol,
glycopyrronium bromide

Filings that have received approval in one of the markets (US or EU) but are awaiting approval in the other market
are included in the table.
2
Refers to lead indication only
3
Phosphoinositide 3-kinase inhibitor
4
Mammalian target of rapamycin
5
Diffuse large B-cell lymphoma
1

Cyclin-dependent kinase 4/6

Conditional on completion of the previously announced transactions with GSK, we expect to return our rights in MEK162 to Array BioPharma Inc.
Combination of mitogen-activated protein kinase and extracellular signal-regulated kinase
Low-grade serous ovarian cancer
10
Anaplastic lymphoma kinase
11
Submission pending acceptance by FDA
6
7
8

50 | Novartis Annual Report 2014

innovation

Novartis Annual Report 2014 | 51

innovation | pipeline

pipeline
continued

glossAry

MAJOR DEVELOPMENT PROJECTS

PHASE l PHASE ll PHASE lll

Project/product Project refers to the Novartis

reference code (combination of three letters

Submission

Planned
Project/product
Division
Common name
Mechanism of action
Potential indication/disease area
Route of administration filing dates1,2

and three numbers) used for projects in

Immunology and Dermatology

development. Product refers to the brand name

QAW039

for a marketed product.

ACZ885
Pharmaceuticals canakinumab

Anti-interleukin-1
Hereditary periodic fevers
monoclonal antibody

Subcutaneous
2016
injection

Cosentyx (AIN457)
Pharmaceuticals secukinumab

Anti-interleukin-17
monoclonal antibody

Subcutaneous
injection

LDE225
Pharmaceuticals sonidegib

Smoothened receptor/
Advanced basal cell carcinoma
Oral
hedgehog signaling inhibitor

Common name Official international nonproprietary name or generic name for an

Pharmaceuticals

fevipiprant

CRTH2 antagonist

Atopic dermatitis

Psoriasis [lead indication], ankylosing spondylitis,

psoriatic arthritis

Oral

2019

US registration
EU registration
US registration
EU registration

individual molecular entity as designated by

the World Health Organization
Mechanism of action Specific biochemical
interaction with a molecular target such as
a receptor or enzyme, through which a drug
substance produces its pharmacological effect
Potential indication/indications Disease or

Neuroscience
CJM112
Pharmaceuticals

Anti-interleukin-17
Immune disorders
monoclonal antibody

CAD106
Pharmaceuticals
Beta-amyloid-protein therapy
Alzheimers disease

Subcutaneous
2019
injection
Intramuscular
2019
injection

BAF312
Pharmaceuticals siponimod

Sphingosine-1-phosphate
Secondary progressive multiple sclerosis
Oral
2019
receptor modulator

Gilenya
Pharmaceuticals fingolimod

Sphingosine-1-phosphate
Chronic inflammatory demyelinating polyradiculoneuropathy
Oral
2017
receptor modulator

condition for which a compound or marketed

BYM338
Pharmaceuticals bimagrumab
Inhibitor of activin receptor type II

Sporadic inclusion body myositis [lead indication],

Intravenous infusion 2016
hip fracture, sarcopenia

product is in development and is being studied

as a potential therapy

Cell and Gene Therapy

CTL019
Pharmaceuticals tisagenlecleucel-T

CD19-targeted chimeric antigen

receptor T-cell immunotherapy

medicinal preparation is administered into

FCR001
Pharmaceuticals

Inducing stable donor chimerism

Renal transplant
Infusion
2019
and immunological tolerance

the body, such as oral, subcutaneous or

HSC835

Stem cell regeneration

intravenous

Route of administration Path by which a

Pharmaceuticals

Adult and pediatric acute lymphoblastic leukemia

Intravenous
2016
[lead indication], diffuse large B-cell lymphoma

Stem cell transplantation

Infusion

2019

Infectious Diseases

Phase I First clinical trials of a new compound,

H7N912

generally performed in a small number of

Acellular pertussis
Vaccines
Tdap vaccine
Pediatric
Prevention of tetanus, diphtheria and pertussis
Intramuscular
2015
combination

healthy human volunteers, to assess the clinical

safety and tolerability, as well as metabolic and
pharmacologic properties of the compound
Phase II Clinical studies with patients who have
the target disease, with the aim of continuing
the Phase I safety assessment in a larger group,
assessing the efficacy of the drug in the patient
population, and determining the appropriate
doses for further evaluation

C. difficile13

Vaccines

Vaccines

H7N9 vaccine

C. difficile vaccine

Pandemic influenza

Hospital infections

Prevention of H7N9 influenza

Prevention of C. difficile disease

Intramuscular

Intramuscular

2015

2015

Human
Vaccines
HIV vaccine
HIV
Prevention of HIV disease
Intramuscular
2015
immunodeficiency
virus (HIV)14
S. aureus

Prevention of S. aureus disease

Intramuscular

KAF156 Pharmaceuticals

Vaccines

S. aureus vaccine

Hospital infections

Malaria

Oral 2019

2015

KAE609 Pharmaceuticals
cipargamin PfATP4 inhibitor

Malaria

Oral 2017

Group B streptococcus Vaccines

Group B streptococcus
Maternal
Prevention of group B streptococcus
Intramuscular
2015
vaccine
H5N1 influenza
Vaccines
Pandemic influenza vaccine Pandemic
Prevention of H5N1 influenza
Intramuscular
2015
cell culture vaccine12
MenABCWY
Vaccines

Meningococcal A, B, C, W Meningitis
Prevention of meningococcal A, B, C, W and Y disease
Intramuscular
2015
and Y vaccine

P. aeruginosa13

Vaccines

P. aeruginosa vaccine

Prevention of P. aeruginosa disease

Intramuscular

2015

Cell culture QIV

Vaccines

Seasonal influenza vaccine Seasonal influenza

Hospital infections

Prevention of seasonal influenza

Intramuscular

2015

aQIV pediatric

Vaccines

Seasonal influenza vaccine Seasonal influenza

Prevention of seasonal influenza

Intramuscular

2015

Fluad US

Vaccines

Seasonal influenza vaccine Seasonal influenza

Prevention of seasonal influenza

Intramuscular

201411

Flucelvax
Vaccines
Seasonal influenza vaccine Seasonal influenza
Prevention of seasonal influenza
Intramuscular
201411
age 4+ US
Bexsero US

Vaccines

Meningococcal B vaccine

Meningitis

Prevention of meningococcal B disease

Intramuscular

2014

Filings that have received approval in one of the markets (US or EU) but are awaiting approval in the other market
are included in the table.
Refers to lead indication only
11
Submission pending acceptance by FDA
12
Collaboration with United States Department of Health and Human Services
13
Collaboration with Valneva
14
Collaboration with United States National Institutes of Health
1

52 | Novartis Annual Report 2014

innovation

Novartis Annual Report 2014 | 53

innovation | pipeline

pipeline
continued

Phase III Large-scale clinical studies with

MAJOR DEVELOPMENT PROJECTS

several hundred to several thousand patients,

PHASE l PHASE ll PHASE lll

which are conducted to establish the safety

Planned
Project/product
Division
Common name
Mechanism of action
Potential indication/disease area
Route of administration filing dates1,2

and efficacy of the drug-specific indications

Submission

for regulatory approval. Phase III trials also

Ophthalmology

may be used to compare a new drug against

RTH258 Alcon

Anti-VEGF15 single-chain
Wet age-related macular degeneration
Intravitrealinjection 2017
antibody fragment

Lucentis
Pharmaceuticals ranibizumab

Anti-VEGF15 monoclonal
antibody fragment

Choroidal neovascularization and macular edema,16

Intravitreal injection 2016
retinopathy of prematurity (ROP)

OAP030 (Fovista)

Aptamer anti-PDGF17

Wet age-related macular degeneration

a current standard of care to evaluate the overall benefit-risk relationship of the new medicine.
Advanced development Medical device project
for which a positive proof of concept has been

Pharmaceuticals

established and studies are being conducted

EXE844b

to establish the safety, efficacy or performance

EXZ829
Alcon
olopatadine hydrochloride

to address regulatory requirements for obtaining marketing authorization

Submission An application for marketing
approval has already been filed with one or
both of the following regulatory agencies:
FDA (United States), EMA (European Union).

Solution

2016

AcrySof IQ ReSTOR
Alcon

Multifocal, aspheric and cylinder
Cataractous lens replacement with or without presbyopia,
Surgical
2016
Advanced development
Toric 3.0D diopter
correcting intraocular lens
and with astigmatism
US and Japan
range expansion IOL
Alcon

finafloxacin

Anti-infective

Otitis media-tympanostomy tube surgery

Topical

2016 US

Antihistamine and
Allergic conjunctivitis
Topical
Submitted US
mast cell stabilization

AOSept Plus/
Alcon

Disinfection and cleaning
Contact lens care
Lens care
Submitted US
Advanced development US
Clear Care Plus
2016 Japan
with HydraGlyde
AcrySof IQ ReSTOR
Alcon

Toric 2.5D IOL

Multifocal, aspheric and cylinder

correcting intraocular lens

Cataractous lens replacement with or without presbyopia,

Surgical
and with astigmatism

Submitted Japan
Advanced development Japan
2015 US

AcrySof IQ
Alcon

Multifocal aspheric intraocular lens
Cataractous lens replacement with or without presbyopia
Surgical
Submitted US
ReSTOR 2.5D IOL
AcrySof IQ
Alcon

ReSTOR Toric 3.0D IOL

Multifocal, aspheric and cylinder

correcting intraocular lens

Cataractous lens replacement with or without presbyopia,

Surgical
Submitted US
and with astigmatism

Novartis has not yet received marketing

authorization from both regulatory agencies.

Biosimilars

The application contains comprehensive

GP2013
Sandoz
rituximab
Anti-CD20 antibody

Non-Hodgkin lymphoma, chronic lymphocytic leukemia,

Intravenous
rheumatoid arthritis, granulomatosis with polyangiitis
(also known as Wegeners granulomatosis), and
microscopic polyangiitis and others (same as originator)

GP2015
Sandoz etanercept
TNF- inhibitor

Arthritidies (rheumatoid arthritis, ankylosing spondylitis, psoriatic Subcutaneous

arthritis), plaque psoriasis and others (same as originator)

GP2017
Sandoz adalimumab
TNF- inhibitor

Arthritidies (rheumatoid arthritis, ankylosing spondylitis, psoriatic Subcutaneous

arthritis), plaque psoriasis and others (same as originator)

HX575
Sandoz
epoetin alfa
Erythropoiesis-stimulating agent

Chronic kidney disease, chemotherapy-induced anemia

and others (same as originator)

data and information gathered during

human clinical trials and animal studies
conducted through the various phases of drug
development.
Filings that have received approval in one of the markets
(either US or EU ) but are awaiting approval in the other market
are included in the table.

Subcutaneous and US
intravenous

HX575 s.c.
Sandoz
epoetin alfa
Erythropoiesis-stimulating agent
Chronic kidney disease
Subcutaneous



LA-EP2006
Sandoz
pegfilgrastim

Pegylated granulocyte
colony-stimulating factor

EP2006
Sandoz
filgrastim
Granulocyte colony-stimulating factor

EU (extension
nephrology,
appproved as
Binocrit since 2007)

Chemotherapy-induced neutropenia and others

Subcutaneous
(same as originator)
Chemotherapy-induced neutropenia, mobilization of peripheral
blood progenitor cells and others (same as originator)

Subcutaneous and
intravenous

US

Filings that have received approval in one of the markets (US or EU) but are awaiting approval in the other market
are included in the table.
Refers to lead indication only
15
Vascular endothelial growth factor
16
Choroidal neovascularization and macular edema secondary to conditions other than age-related
macular degeneration, diabetic macular edema, retinal vein occlusion and pathologic myopia
17
Anti-platelet-derived growth factor
1