3. INTRODUCTION
Novartis (NYSE: NVS) is a world leader in the research and
development of products to protect and improve health and well-being.
The company has core businesses in pharmaceuticals, vaccines,
consumer health, generics, eye care and animal health
Headquartered in Basel, Switzerland, Novartis employs nearly 115 000
people in over 140 countries worldwide to help save lives and improve
the quality of life. The Group is present in India through Novartis India
Limited, listed on the Mumbai Stock Exchange and its wholly owned
subsidiaries Novartis Healthcare Private Limited, Sandoz Private
Limited and Chiron Behring Vaccines Private Limited.
HISTORY OF NOVARTIS
Novartis was created in 1996 through the merger of Ciba-Geigy and
Sandoz, two companies with a rich and diverse corporate history.
Throughout the years, Novartis and its predecessor companies have
discovered and developed many innovative products for patients and
consumers worldwide.
Novartis has been in India since 1947. The Group operates in India
through four entities namely Novartis India Limited, listed on the
Mumbai Stock Exchange, Novartis Healthcare Private Limited, Sandoz
Private Limited and Chiron-Behring Vaccine Private Limited. In India
Novartis has a presence in pharmaceuticals, generics (pharmaceutical
products that are off patent), Vaccines, OTC (over-the-counter
medicines), eyecare and Animal Health.
4. PRESENT STATUS
Novartis India has reported a standalone sales turnover of Rs 212.85
crore and a net profit of Rs 24.41 crore for the quarter ended Mar '13.
Other income for the quarter was Rs 22.30 crore.For the quarter ended
Mar 2012 the standalone sales turnover was Rs 204.48 crore and net
profit was Rs 32.91 crore., and other income Rs 27.96 crore.Novartis
India shares closed at 575.60 on May 14, 2013 (BSE) and has given -
14.13% returns over the last 6 months and -18.31% over the last 12
months
REMARKABLE ACHIVEMENTS
{1} Novartis Pharmaceutical US chosen for 2013 list of best employers
for mothers.
{2} Novartis was accredited as the first global CEO Cancer Gold
Standard employer by the CEO Roundtable on Cancer.
{3} Award of Excellence for Innovations in Diversity
{4} Fortune 500 rated Novartis as the third largest healthcare company
worldwide.
{5} Novartis enters the list of the 50 preferred employers among
European Engineering/IT students.
5. {6} SMS for Life has been recognized by Sustainia to Novartis as one of
the world's top 100 innovative, sustainable solutions for 2013
{7} Novartis Pharmaceuticals Corporation recognized among the best
employers for diversity in the US in Diversity Inc's Top 50 Companies
for Diversity
{8} Novartis ranked top pharmaceutical company in Fortune's World's
Most Admired Companies 2013 for the third time in a row.
{9} Novartis recognized as having the "Most Innovative Pipeline" for
the third consecutive year.
{10} Novartis is a member of the 2012/13 Dow Jones Sustainability
World Index, which recognizes the leading sustainability-driven
companies worldwide.
{11} Novartis awarded two of the prestigious SCRIP Awards for
excellence in innovation and R&D
{12} Novartis is the greenest healthcare company worldwide
{13} Novartis ranked no. 11 on Science's Top 20 Employers list.
{14} Novartis brand ranks no. 39 globally and no. 2 in Switzerland.
6. {15} Novartis named one of the top 50 most attractive employers
worldwide for engineering students by Universum .
{16} Novartis named the most transparent large healthcare company
by Transparency International
{17} Novartis wins Ethical Corporation Award for Best Corporate/NGO
Partnership for SMS for Life
{18} Novartis ranks again as the most respected healthcare company
in "The World's Most Respected Companies" by US business magazine
Barron's
{19} Novartis again ranked No. 1 employer in Switzerland for students
in Natural Science by Swiss business magazine Bilanz and Universum
{20} Novartis is No. 2 in Pharm Exec's 2012 ranking of the top 50
pharma companies based on Rx sales.
{21} Novartis CEO Joseph Jimenez receives "CEO in Action" award for
commitment and engagement in Novartis Diversity & Inclusion
initiatives.
7. MOST VISIBLE PRODUCTS OF NOVARTIS
{1} GALVUS - PRICE OF GALVUS 50 mg RS 586.04
Galvus® (vildagliptin) is approved in more than 100 countries
across Europe, Asia Pacific, Africa and Latin America . It is
indicated for the treatment of type 2 diabetes as a monotherapy
and in combination with metformin, a sulphonylurea, a
thiazolidinedione or insulin. Specific indications vary by country.
SALES OF GALVUS
Novartis believes that Galvus will be one of the drugs that will
offset the loss of revenues from patent expirations, notably on its
biggest-seller, the blood pressure lowerer Diovan (valsartan).
Galvus generated sales of $677 million, a rise of 66% and this
despite not being available in the USA.
MECHANISM OF ACTION OF GALVUS
Vildagliptin is indicated in the treatment of type 2 diabetes
mellitus in adults. Vildagliptin is also indicated for use in
8. combination with insulin (with or without metformin) when diet
and exercise plus a stable dose of insulin do not provide
adequate glycemic control. Vildagliptin, a member of the islet
enhancer class, is a potent and selective DPP-4 inhibitor. The
administration of vildagliptin results in a rapid and complete
inhibition of DPP-4 activity, resulting in increased fasting and
postprandial endogenous levels of the incretin hormones GLP-1
(glucagon-like peptide 1) and GIP (glucose-dependent
insulinotropic polypeptide).
ROUTE OF ADMINISTRATION AND DOSSAGE OF GALVUS
The recommended dose of vildagliptin is 50mg once daily administered
in the morning . Doses higher than 100mg are not recommended.
If a dose of Galvus is missed, it should be taken as soon as the patient
remembers. A double dose should not be taken on the same day.
The safety and efficacy of vildagliptin as triple oral therapy in combination
with metformin and a thiazolidinedione have not been established . GALVUS
is administered by Oral use Galvus can be administered with or without
a meal
PHARMACODYNAMICS
By increasing the endogenous levels of these incretin hormones,
vildagliptin enhances the sensitivity of beta cells to glucose, resulting
in improved glucose-dependent insulin secretion. Treatment with
vildagliptin 50-100mg daily in patients with type 2 diabetes
significantly improved markers of beta cell function including HOMA-β
(Homeostasis Model Assessment–β), proinsulin to insulin ratio and
measures of beta cell responsiveness from the frequently-sampled
meal tolerance test. In non-diabetic (normal glycaemic) individuals,
vildagliptin does not stimulate insulin secretion or reduce glucose
levels. By increasing endogenous GLP-1 levels, vildagliptin also
enhances the sensitivity of alpha cells to glucose, resulting in more
glucose-appropriate glucagon secretion. The enhanced increase in the
insulin/glucagon ratio during hyperglycaemia due to increased incretin
hormone levels results in a decrease in fasting and postprandial
hepatic glucose production, leading to reduced glycaemia.
9. {2} DIOVAN 80 mg – PRICE OF DIOVAN RS 616.98
MECHANISM OF ACTION OF DIOVAN
Valsartan {DIOVAN} is an oral medication that is used to treat
high blood pressure and congestive heart failure. It belongs to a
class of drugs called angiotensin receptor blockers (ARBs).
Angiotensin, formed in the blood by the action of angiotensin
converting enzyme (ACE), is a powerful chemical that attaches to
angiotensin receptors found in many tissues but primarily on
smooth muscle cells of blood vessels. Angiotensin's attachment
to the receptors causes the blood vessels to narrow
(vasoconstrict) which leads to an increase in blood pressure
(hypertension). Valsartan blocks the angiotensin receptor. By
blocking the action of angiotensin, valsartan dilates blood
vessels and reduces blood pressure.
SALES OF DIOVAN
Global sales for DIOVAN 80 Mg were approximately $5000 million
10. ROUTE OF ADMINISTRATION AND DOSSAGE OF DIOVAN
DIOVAN is administered by ORAL route
The usual dose of valsartan for adults with high blood pressure is
80 to 160 mg once daily. The maximum dose is 320 mg daily.
Maximum blood pressure reduction occurs within 4 weeks. For
congestive heart failure, the usual dose is 40 mg twice daily. The
doses may be increased to 80-160 mg twice daily. The initial
dose after a heart attack is 20 mg twice daily. The dose may be
increased to 160 mg twice daily if tolerated without side effects
PHARMACODYNAMICS
Valsartan inhibits the pressor effect of angiotensin II infusions. An oral
dose of 80 mg inhibits the pressor effect by about 80% at peak with
approximately 30% inhibition persisting for 24 hours Removal of the
negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma
renin and consequent rise in angiotensin II plasma concentration in
hypertensive patients.
Minimal decreases in plasma aldosterone were observed after
administration of valsartan; very little effect on serum potassium was
observed. In multiple-dose studies in hypertensive patients with stable
renal insufficiency and patients with renovascular hypertension,
valsartan had no clinically significant effects on glomerular filtration
rate, filtration fraction, creatinine clearance, or renal plasma flow In
multiple-dose studies in hypertensive patients, valsartan had no
notable effects on total cholesterol, fasting triglycerides, fasting
serum glucose, or uric acid.
11. {3} TEGRETOL 100 Mg – PRICE OF TEGRETOL 100 mg RS 10.10
MECHANISM OF ACTION
Tegretol has demonstrated anticonvulsant properties in rats and mice
with electrically and chemically induced seizures. It appears to act by
reducing polysynaptic responses and blocking the post-tetanic
potentiation Tegretol greatly reduces or abolishes pain induced by
stimulation of the infraorbital nerve in cats and rats. It depresses
thalamic potential and bulbar and polysynaptic reflexes, including the
linguomandibular reflex in cats. Tegretol is chemically unrelated to
other anticonvulsants or other drugs used to control the pain of
trigeminal neuralgia. The principal metabolite of Tegretol
carbamazepine-10,11-epoxide, has anticonvulsant activity as
demonstrated in several in vivo animal models of seizures. Though
clinical activity for the epoxide has been postulated, the significance
of its activity with respect to the safety and efficacy of Tegretol has
not been established
Sales of TEGRETOL 100mg is $413 million
ROUTE OF ADMINISTRATION AND DOSSAGE OF TEGRETOL100
Tegretol is given orally, usually in two or three divided doses. Tegretol
may be taken during, after or between meals, with a little liquid e.g. a
glass of water. Tegretol should be taken in a number of divided doses
although initially 100-200mg once or twice daily is recommended. This
may be followed by a slow increase until the best response is obtained
12. PHARMACODYNAMICS
Therapeutic class: Anti-epileptic, neurotropic and psychotropic agent
Dibenzazepine derivative.
As an antiepileptic agent its spectrum of activity embraces: partial
seizures (simple and complex) with and without secondary
generalisation; generalised tonic-clonic seizures, as well as
combinations of these types of seizures.
The mechanism of action of carbamazepine, the active substance of
Tegretol, has only been partially elucidated. Carbamazepine stabilises
hyperexcited nerve membranes, inhibits repetitive neuronal
discharges, and reduces synaptic propagation of excitatory impulses.
It is conceivable that prevention of repetitive firing of sodium-dependent
action potentials in depolarised neurons via use- and
voltage-dependent blockade of sodium channels may be its main
mechanism of action.
Whereas reduction of glutamate release and stabilisation of neuronal
membranes may account for the antiepileptic effects, the depressant
effect on dopamine and noradrenaline turnover could be responsible
for the antimanic properties of carbamazepine
13. {4} FEMARA – PRICE OF FEMARA 2.5mg RS 1986.00
MECHANISM OF ACTION
LETROZOLE is an oral non - steroidal aromatase inhibitor for the
treatment of hormonally responsive breast cancer after surgery
Estrogens are produced by the conversion of androgens through
the activity of the aromatase enzyme. Estrogens then bind to an
estrogen receptor, which causes cells to divide.
SALES TURNOVER OF FEMARA $937 million
ROUTE OF ADMINISTRATION AND DOSSAGE OF FEMARA
The recommended dose of Femara (letrozole tablets) is one 2.5 mg
tablet administered once a day, without regard to meals. In patients
with advanced disease, treatment with Femara should continue until
tumor progression is evident. And Femara is administered orally
14. PHARMACODYNAMICS
In postmenopausal patients with advanced breast cancer, daily doses
of 0.1 mg to 5 mg Femara suppress plasma concentrations of
estradiol, estrone, and estrone sulfate by 75%-95% from baseline with
maximal suppression achieved within two-three days. Suppression is
dose-related, with doses of 0.5 mg and higher giving many values of
estrone and estrone sulfate that were below the limit of detection in
the assays. Estrogen suppression was maintained throughout
treatment in all patients treated at 0.5 mg or higher. Letrozole is highly
specific in inhibiting aromatase activity. There is no impairment of
adrenal steroidogenesis. No clinically-relevant changes were found in
the plasma concentrations of cortisol, aldosterone, 11-deoxycortisol,
17-hydroxy-progesterone, ACTH or in plasma renin activity among
postmenopausal patients treated with a daily dose of Femara 0.1 mg
to 5 mg. The ACTH stimulation test performed after 6 and 12 weeks of
treatment with daily doses of 0.1, 0.25, 0.5, 1, 2.5, and 5 mg did not
indicate any attenuation of aldosterone or cortisol production.
Glucocorticoid or mineralocorticoid supplementation is, therefore, not
necessary. No changes were noted in plasma concentrations of
androgens (androstenedione and testosterone) among healthy
postmenopausal women after 0.1, 0.5, and 2.5 mg single doses of
Femara or in plasma concentrations of androstenedione among
postmenopausal patients treated with daily doses of 0.1 mg to 5 mg.
This indicates that the blockade of estrogen biosynthesis does not
lead to accumulation of androgenic precursors. Plasma levels of LH
and FSH were not affected by letrozole in patients, nor was thyroid
function as evaluated by TSH levels, T3 uptake, and T4 levels
15. {5} GLIVEC – PRICE OF GLIVEC 400 mg RS 1371.73
MECHANISM OF ACTION OF GLIVEC
Imatinib is a small molecule kinase inhibitor. Glivec film-coated
tablets contain imatinib mesylate 400 mg of imatinib free base.
Imatinib mesylate is designated chemically as 4-[(4-Methyl- 1-
piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-
pyrimidinyl]amino]-phenyl]benzamide methanesulfonate and its
structural formula is
16. Imatinib is a 2-phenyl amino pyrimidine derivative that functions
as a specific inhibitor of a number of tyrosine kinase enzymes. It
occupies the TK active site, leading to a decrease in activity.
There are a large number of TK enzymes in the body, including
the insulin receptor. Imatinib is specific for the TK domain in abl
(the Abelson proto-oncogene), c-kit and PDGF-R (platelet-derived
growth factor receptor). In chronic myelogenous leukemia, the
Philadelphia chromosome leads to a fusion protein of abl with bcr
(breakpoint cluster region), termed bcr-abl. As this is now a
constitutively active tyrosine kinase, imatinib is used to
decrease bcr-abl activity. The active sites of tyrosine kinases
each have a binding site for ATP. The enzymatic activity
catalyzed by a tyrosine kinase is the transfer of the terminal
phosphate from ATP to tyrosine residues on its substrates, a
process known as protein tyrosine phosphorylation. Imatinib
works by binding close to the ATP binding site of bcr-abl, locking
it in a closed or self-inhibited conformation, and therefore
inhibiting the enzyme activity of the protein semi-competitively.
This fact explains why many BCR-ABL mutations can cause
resistance to imatinib by shifting its equilibrium toward the open
or active conformation. Imatinib is quite selective for bcr-abl – it
does also inhibit other targets mentioned above (c-kit and PDGF-R),
but no other known tyrosine kinases. Imatinib also inhibits
the abl protein of non-cancer cells but cells normally have
additional redundant tyrosine kinases which allow them to
continue to function even if abl tyrosine kinase is inhibited. Some
tumor cells, however, have a dependence on bcr-abl. Inhibition of
the bcr-abl tyrosine kinase also stimulates its entry in to the
nucleus, where it is unable to perform any of its normal anti-apoptopic
functions. The Bcr-Abl pathway has many downstream
pathways including the Ras/MapK pathway, which leads to
increased proliferation due to increased growth factor-independent
cell growth. It also affects the Src/Pax/Fak/Rac
17. pathway. This affects the cytoskeleton, which leads to increased
cell motility and decreased adhesion. The PI/PI3K/AKT/BCL-2
pathway is also affected. BCL-2 is responsible for keeping the
mitochondria stable; this suppresses cell death by apoptosis and
increases survival. The last pathway that Bcr-Abl affects is the
JAK/STAT pathway, which is responsible for proliferation.
SALES TURNOVER OF GLIVEC $3100 million
ROUTE OF ADMINISTRATION AND DOSSAGE OF GLIVEC 400
Therapy should be initiated by a physician experienced in the
treatment of patients with hematological malignancies or
malignant sarcomas, as appropriate. The prescribed dose should
be administered orally, with a meal and a large glass of water.
Doses of 400 mg should be administered once daily dose of 800
mg should be administered as 400 mg twice a day. In CML, a
dose increase from 400 mg to 600 mg in adult patients with
chronic phase disease, or from 600 mg to 800 mg (given as 400
mg twice daily) in adult patients in accelerated phase or blast
crisis may be considered in the absence of severe adverse drug
reaction and severe non-leukemia related neutropenia or
thrombocytopenia in the following circumstances: disease
progression (at any time), failure to achieve a satisfactory
hematologic response after at least 3 months of treatment,
failure to achieve a cytogenetic response after 6-12 months of
treatment, or loss of a previously achieved hematologic or
cytogenetic response.
18. PHARMACODYNAMICS
Imatinib is an antineoplastic agent used to treat chronic
myelogenous leukemia. Imatinib is a 2-phenylaminopyrimidine
derivative that functions as a specific inhibitor of a number of
tyrosine kinase enzymes. In chronic myelogenous leukemia, the
Philadelphia chromosome leads to a fusion protein of Abl with
Bcr (breakpoint cluster region), termed Bcr-Abl. As this is now a
continuously active tyrosine kinase, Imatinib is used to decrease
Bcr-Abl activity
