Roche Annual Report 2010

Pharmaceuticals | Solid localcurrency
growth in sales of strategic products
and core operating profit despite lower
Tamiflu revenues and a tougher market
environment, additional approvals for
key medicines and progress with promising
projects in our late-stage development
pipeline made 2010 a successful year.
The Pharmaceuticals Division is focused on
translating excellence in science into effective
medicines for patients. It combines cuttingedge
research at Roche, Genentech in the
US, Chugai in Japan and over 150 partners
worldwide with global scale and reach
in clinical development, manufacturing and
commercial operations.

Pharmaceuticals
Roche Business Report 2010
25­
Pharmaceuticals Division in brief
Sales | in millions of CHF
Core operating profit | in millions of CHF
Number of employees
35,961
38,996
37,058
13,594
14,836
14,776
54,813
54,141 53,187
08 09 10
08 09 10
08 09 10
Key figures
In millions of CHF
% change
in CHF
% change in
local currencies
% of sales
Sales 37,058 –5 –2 100
— United States 14,071 –5 –1 38
— Western Europe 9,467 –13 –5 25
— Japan 4,319 –9 –12 12
— International (Asia—Pacific, CEMAI 1 ,
Latin America, Canada, Others)
9,201 7 8 25
Core operating profit 14,776 0 4 39.9
Operating free cash flow 12,933 –13 –9 34.9
Research and development (core basis) 8,160 –5 –2 22.0
1 CEMAI: Central and Eastern Europe, Middle East, Africa, Central Asia, Indian Subcontinent.
Pharmaceuticals Management Team | 31 December 2010
Pascal Soriot 1, 2
Hal Barron 2
Ian Clark 2
Tuygan Göker 2
Meeta Gulyani 2
Peter Hug 2
Michael Knierim 2
David Loew 2
Luke Miels 2
Patrick Mongrolle 2
Jörg Rupp 2
Patrick Yang 2
Chief Operating Officer Pharmaceuticals, Head of Pharma Medicines
Global Product Development, Chief Medical Officer
Commercial Operations, North America and CEO, Genentech
Commercial Operations, CEMAI
Global Portfolio Management
Commercial Operations, Western Europe
Human Resources
Global Product Strategy
Commercial Operations, Asia—Pacific
Finance
Commercial Operations, Latin America
Global Technical Operations
Jean-Jacques Garaud 1
Osamu Nagayama 1
Richard Scheller 1
Dan Zabrowski 1
Pharma Research and Early Development (pRED)
President and CEO, Chugai
Genentech Research and Early Development (gRED)
Roche Partnering
1 Member of the Corporate Executive Committee — see Corporate Governance, p. 84–85.
2 Member of the Pharma Medicines Leadership Team.

26­ Roche Business Report 2010 Pharmaceuticals
Pharmaceuticals Division
Solid local-currency growth 1 in sales of strategic
products and core operating profit, additional marketing
approvals for strategic products, and progress
with a range of promising projects in our late-stage
R & D pipeline made 2010 a successful year overall
for the Pharmaceuticals Division. Growth was driven
primarily by strong demand for key medicines from
the Group’s oncology and inflammatory disease portfolios.
Following the end of the influenza A (H1N1)
pandemic and completion of government stockpiling
orders, sales of Tamiflu declined strongly.
We achieved important product development successes
in 2010, including expanded marketing
ap­prov­als for Actemra/RoActemra for rheumatoid
arthritis in the US and the EU, Herceptin for stomach
cancer (EU and US), MabThera/Rituxan for chronic
lymphocytic leukemia (US) and maintenance treatment
of follicular lymphoma (EU), and Lucentis for
macular edema following retinal vein occlusion (US).
Key regulatory filings included marketing applications
for Actemra/RoActemra for juvenile idiopathic
arthritis in the EU and US, Herceptin for stomach
cancer in Japan and Avastin for advanced ovarian
cancer in the EU.
During the year we made decisions to move several
projects into late-stage development, including
­ocrelizumab for multiple sclerosis, RG7128 for hep-­
atitis C, lebrikizumab for asthma and RG3638 ­
(MetMAb) for lung cancer. Positive results from clin-­
ical trials with other late-stage compounds such ­
as RG7204 (BRAF inhibitor) for melanoma, RG7159
(GA101) for non-Hodgkin’s lymphoma and chronic
lymphocytic leukemia, and T–DM1 and pertuzumab
for HER2-positive breast cancer were published or
presented at major medical conferences during 2010.
These targeted compounds are designed to move ­
the standard of care for these diseases and improve
patient survival. Roche’s pharmaceutical pipeline
­currently includes 12 new molecular entities in latestage
development.
Sales by region
United States 38% (–1%)
Asia—Pacific 6% (+8%)
Latin America 7% (+20%)
Other regions 3% (–9%)
CEMAI 9% (+4%)
Western Europe 25% (–5%)
Japan 12% (–12%)
Italics = growth rates (local currencies).
CEMAI: Central and Eastern Europe, Middle East, Africa,
Central Asia, Indian Subcontinent.
At the same time, 2010 was a year of significant
­challenges. Pressure on healthcare budgets in many
countries and healthcare reforms in the United
States, the world’s largest market for pharmaceuticals,
translated into mandatory reductions in reimbursement
prices or higher rebates on medicines
under statutory health insurance or governmentfunded
programmes. These developments already
had a noticeable impact on sales in 2010, and ­
we expect this to continue into 2011 and beyond. ­
In addition, we experienced several product development
setbacks in 2010. The most serious of ­
these were the decision to suspend phase III testing
of taspoglutide for type 2 diabetes, and regulatory
developments in the US and EU concerning Avastin
as a treatment for advanced breast cancer.
In December the European and US health authorities
announced decisions that are pivotal in determining
whether Avastin remains available as a treatment ­
for metastatic breast cancer. We believe strongly that
patients should have this option and are pleased ­
that the European authorities continue to support the
use of Avastin in this indication. It is disappointing
that the US Food and Drug Administration (FDA) has
come to a different conclusion after reviewing the
same set of data. We believe that women with HER2-
negative metastatic breast cancer living in the US
should also have Avastin as a treatment option, and
we have requested a hearing with the FDA accordingly
(see p. 37).
Responding to the tougher operating environment
and setbacks outlined above, we continued to
strengthen our Pharmaceuticals organisation to
1 Unless otherwise stated, all growth rates are in local currencies.

Pharmaceuticals
Roche Business Report 2010
27­
increase efficiency and maintain its focus on innovation.
We believe that the measures now being
implemented through the Group’s Operational Excellence
programme will enhance Roche’s ability to
deliver breakthrough medicines for patients, allowing
us to expand further in high-growth emerging economies
while strengthening our presence in established
markets.
Results and main
business developments
Sales by the Pharmaceuticals Division in 2010
declined 2% in local currencies (–5% in Swiss francs,
–1% in US dollars) compared with 2009 to 37.1 billion
Swiss francs. Excluding Tamiflu, the division’s
local-currency sales grew 5%, above the global ­
market. In addition to the Group’s five main cancer
medicines, the primary sales drivers were Lucentis,
Actemra/RoActemra and Mircera. Growth from these
and other pharmaceuticals largely compensated ­
for lower sales of Tamiflu, CellCept and NeoRecormon/Epogin.
Together, the top six sales drivers —
Avastin, MabThera/Rituxan, Herceptin, Lucentis,
Actemra/RoActemra and Xeloda — contributed over
1.3 billion Swiss francs in additional sales in 2010.
Due to the passing of the influenza A (H1N1) pandemic,
a relatively mild influenza season and the
completion of most government stockpiling orders,
sales of Tamiflu declined strongly, to 873 million
Swiss francs (2.3 billion francs lower than in 2009).
Sales expanded fastest in the International region
(8%, or 11% excluding Tamiflu), driven by demand for
MabThera, Herceptin, Avastin and other key medicines
in emerging markets. Particularly strong growth
was recorded in Latin America (20%), led by Brazil
and Venezuela. Solid growth in the Asia—Pacific
region (8%) was led by China and Taiwan. A slight
decrease in the United States (–1%) reflects significantly
lower sales of Tamiflu and CellCept, as well
as healthcare reform impacts affecting all major
products. A 5% decline in sales in Western Europe
was due primarily to markedly lower sales of Tamiflu
and NeoRecormon and the effects of government
austerity measures introduced in a number of countries,
including Greece and Spain in the second
quarter and Germany in the third quarter. Together,
Excluding Tamiflu, Pharmaceuticals
Division sales grew 5%,
above the global market.
healthcare reforms in the United States and austerity
measures in Europe had a negative impact on total
sales of approximately 530 million Swiss francs or ­
1.5 percentage points. Excluding Tamiflu, sales in the ­
US and Western Europe increased 4% and 2%,
respectively, compared with market growth 2 of 3%
and 2%. A decline in sales of 12% in Japan reflects
both significantly lower demand for Tamiflu and ­
the impact of revised National Health Insurance reimbursement
prices that came into effect in April.
Excluding Tamiflu, Japanese sales grew 3% in a virtually
flat market.
Core operating profit 3 grew 4% in local currencies
and was stable in Swiss francs at 14.8 billion Swiss
francs. The corresponding margin increased 1.9
­percentage points to 39.9%, driven by synergies from
the merger with Genentech and productivity improvements.
This was achieved despite the expected sharp
decline in Tamiflu sales and the impact of health­-­
care reforms and austerity measures. A reduction of
1% in marketing expenses was achieved through
tight cost management, which more than covered ­
an increase in allowances for bad debts in Southern
Europe. Research and development expenses
declined 2% versus 2009 thanks to resource priori-­
tisation while securing long-term growth through ­
the rich R & D pipeline. In addition to investments in
phase III initiations, the metabolism franchise and ­
the earlier-stage neurology portfolio, research and
development expenses included costs associated
with the discontinuation of the ocrelizumab rheumatoid
arthritis programme (see p. 51, below) and
project termination costs associated with the Operational
Excellence programme.
2 Pharmaceutical market growth according to IMS
(to end of September 2010).
3 Unless otherwise stated all results are on a core basis
(see p. 14, above, and p. 144 of the Finance Report).

28­ Roche Business Report 2010 Pharmaceuticals
The core operating profit
margin increased 1.9 percentage
points to 39.9%.
The division’s full-year operating free cash flow
remained strong at 12.9 billion Swiss francs. The
decrease of 9% compared with 2009 primarily
reflects the payment in 2010 of certain large 2009
year-end accruals, including employee retention ­
and severance payments, and high royalty payments
relating to strong Tamiflu sales in the second half ­
of 2009. The Pharmaceuticals Division is on track to
achieve its goal of pre-tax annual synergies from ­
the Genentech merger of approximately 1 billion
Swiss francs by 2011. Synergies of over 800 million
Swiss francs were achieved in 2010. For more
­information on the division’s operating results, ­
see the Finance Report (Part 2 of this Annual ­
Report).
In the year under review the Pharmaceuticals ­
Division incurred significant non-core costs associated
with restructuring measures implemented ­
under the Operational Excellence programme. Most
of these costs relate to severance payments following
reductions in positions in sales and marketing,
global manufacturing, global development, ­
and research and early development, as well as
impairments of intangible assets.
Manufacturing infrastructure
Integration of the Roche and Genentech manufacturing
and supply networks continued in 2010, as
­initiatives were implemented to ensure that global
demand for commercial and clinical supplies of ­
our medicines can be met and that necessary adaptations
to our growing pipeline are made in time.
A number of important milestones were achieved ­
in 2010. In April Hillsboro Operations (Oregon, USA)
was officially inaugurated. By 2013 Hillsboro will ­
be the US commercial filling and packaging facility
for our medicines, supplementing facilities in
­Germany and Switzerland. In addition, expansion ­
of the Kentucky Distribution Center was completed
in 2010. The facility now serves as the primary
­distribution centre for all products marketed in the
United States.
In all, Global Technical Operations facilities passed
more than 30 health authority inspections in 2010.
Our biotech production facility in Singapore received
its first approvals by the US Food and Drug Administration
(FDA), to manufacture Lucentis and Avastin
biologic bulk drug substance for commercial use ­
in the US. Approval by the EU authorities is targeted
for 2011. Our Kaiseraugst (Switzerland) facility
­successfully launched Actemra product for commercialisation
in the United States 14 days after FDA
approval. Our bulk drug manufacturing facilities in
South San Francisco, Vacaville and Oceanside ­
(California, USA) received Class A certification, an
international business award recognising system­-­
atic process improvements.
As part of the continuous evaluation of our global
manufacturing network, we are always reviewing and
analysing our structures, organisations, processes
and operations. In 2010 we sold facilities located in
Isando (South Africa) and Karachi (Pakistan). In
addition, plants in Montevideo (Uruguay) and Nutley
(New Jersey, USA) were closed, and we continue ­
to plan for the closure of certain operations in Mannheim
(Germany) and Basel (Switzerland).
Following a detailed analysis of organisational
­structures and processes as part of the Group-wide
Operational Excellence programme, Global Technical
Operations will further refine its organisational
­structure to improve operational efficiencies, optimise
manufacturing assets and consolidate the
­technical development and clinical supply network.
Some activities will be reorganised in California,
Mannheim and other sites by the end of 2013, resulting
in a reduction of approximately 750 positions. ­
In addition, Roche intends to seek buyers for its US
sites in Florence, South Carolina, and Boulder,
­Colorado, potentially affecting an additional 600 jobs.
Together with activities initiated in the last two ­
years, these changes will reduce the number of
­manufacturing locations from 21 to 15 by the ­
end of 2013.

Pharmaceuticals
Roche Business Report 2010
29­
Sales by therapeutic area
Oncology 57% (+7%)
Inflammatory and autoimmune diseases, transplantation 8% (+3%)
Central nervous system 3% (+2%)
Respiratory 3% (+7%)
Metabolic diseases, bone diseases 7% (–1%)
Infectious diseases 1% (–2%)
Cardiovascular diseases 3% (–3%)
Virology 10% (–39%)
Others 1% (–10%)
Renal anemia 3% (–6%)
Ophthalmology 4% (+27%)
Italics = growth rates (local currencies).
Partnering activities
Collaboration with external partners has long been ­
a cornerstone of Roche’s R & D strategy. Access ­
to external innovation through licensing and targeted
acquisitions is a significant means of strengthening
the R & D portfolio and expanding the Group’s technology
capabilities. In 2010 Roche Partnering signed
a total of 52 new agreements, including one prod­-­
uct transaction and 40 research and technology collaborations.
In addition, ten product outlicensing
agreements were signed.
Among Roche Partnering’s main transactions in 2010
were an agreement with Belgian company reMYND
to develop novel therapeutics that could slow down
neurodegeneration in Parkinson’s and Alzheimer’s
patients. A new collaboration was agreed with Aileron
Therapeutics to discover, develop and commercial-­
ise a novel class of drugs called stapled peptide ther-­
apeutics, a potentially transfor­mative technology ­
to create drugs for important disease targets that are
intractable to currently available modalities. In
December Roche acquired Marcadia Biotech, a privately
owned US company focusing on the devel-­
opment of innovative therapeutics for ­metabolic ­
diseases. Marcadia’s research and development programmes
on new peptide therapies for the treatment
of type 2 diabetes and obesity will be integrated ­
into Roche’s R & D portfolio. These include next gener-­
ation peptides such as MAR701, currently in phase I
development for type 2 diabetes. Several partners
were added to Roche’s Expanding the Innovation
Network (EIN) project, which is designed to create
and deepen relations with leading academic insti-­
tutions worldwide. Under a new EIN partnership with
Harvard University, Roche provides strategic questions
and know-how to Harvard, with Harvard providing
innovative solutions.
Genentech Partnering completed four product transactions
and 16 research and technology collaborations
in 2010, supporting the cutting-edge work ­
of Genentech Research and Early Development.
Among these is an expansion of the antibody-drug
conjugate collaboration with Seattle Genetics in
oncology. New collaborations in immunology
included an exclusive licensing agreement with
Swiss-based antibody specialist NovImmune, covering
an anti-IL-17 antibody that has the potential ­
to benefit patients across a range of autoimmune diseases.
A novel research programme was agreed ­
with US company Adimab, which will use its proprietary
discovery platform to identify fully human antibodies
against two targets selected by Genentech.
Under the agreement, Genentech has rights to
­commercialise antibodies generated from the collaboration.
Sales review —
selected key products
The Pharmaceuticals Division’s broad-based portfolio
of marketed products includes ten medicines from

30­ Roche Business Report 2010 Pharmaceuticals
Top-selling pharmaceuticals — Roche Group | in millions of CHF
6,461 6,356 5,429 1,645 1,458
Avastin MabThera/Rituxan Herceptin Pegasys Lucentis **
+9% *
+9% *
+7% *
+2% *
+27% *
Active substance:
bevacizumab 1
Active substance:
rituximab 1
Active substance:
trastuzumab 1
Active substance:
peginterferon alfa-2a 1
Active substance:
ranibizumab 1
Indications:
colorectal cancer,
breast cancer, non-small
cell lung cancer, kidney
cancer, glioblastoma
Indications:
non-Hodgkin’s lymphoma,
chronic lymphocytic
leukemia, rheumatoid
arthritis
Indications:
HER2-positive breast cancer,
advanced HER2-positive
stomach cancer
Indications:
hepatitis B and C
Indications:
wet age-related macular
degeneration, macular
edema following retinal
vein occlusion

Pharmaceuticals
Roche Business Report 2010
31­
Thanks to the Pharmaceuticals Division’s broad-based
portfolio, Roche is one of the world’s leading providers of
clinically differentiated medicines for cancer, viral
and inflammatory diseases, and metabolic disorders.
1,426 1,325 1,290 1,285 1,013
Xeloda Tarceva CellCept NeoRecormon, Epogin Bonviva/Boniva
+17% *
+6% *
–15% *
–15% *
+1% *
Active substance:
capecitabine 2
Active substance:
erlotinib 2
Active substance:
mycophenolate mofetil 2
Active substance:
epoetin beta 1
Active substance:
ibandronate 2
Indications:
colorectal cancer, breast
cancer, stomach cancer
Indications:
advanced non-small cell
lung cancer, advanced
pancreatic cancer
Indications:
transplantation
Indications:
anemia
Indications:
osteoporosis
1,2 The images above show molecular diagrams representing the active
substance of each medicine (1 = therapeutic protein, 2 = small molecule).
* Year-on-year sales growth in local currencies.
** US sales. Lucentis is marketed outside the United States by Novartis.

32­ Roche Business Report 2010 Pharmaceuticals
six therapeutic areas that generated sales of over ­
1 billion Swiss francs each in 2010. Of these, the top
three recorded sales of well over 5 billion Swiss
francs each. Combined sales of the Group’s top 20
pharmaceuticals amounted to 32.6 billion Swiss
francs, or 88% of divisional sales.
Sales of the division’s oncology portfolio rose 7% to
21.3 billion Swiss francs in 2010, led by key products
Avastin, MabThera/Rituxan, Herceptin, Xeloda and
Tarceva. Together, these five medicines accounted for
over half of total pharmaceutical sales. Sales of
­antiviral medicines declined 39%, for a full-year total
of 3.5 billion Swiss francs, due mainly to the sharp
decline in sales of Tamiflu. Overall sales of the renal
anemia portfolio declined by 6% to 1.2 billion francs,
with strong demand for Mircera outweighed by
decreasing sales of NeoRecormon/Epogin. Sales in
the combined inflammation/autoimmune/transplantation
portfolio rose 3% to 3.0 billion francs: growing
demand for MabThera/Rituxan for rheumatoid ­
arthritis and strong uptake of Actemra/RoActemra
offset continued generic erosion of CellCept in the
United States.
Oncology
Global sales of Avastin (bevacizumab), for advanced
colorectal, breast, lung and kidney cancer, and for
relapsed glioblastoma (a type of brain tumour), rose
9% to 6.5 billion Swiss francs, reflecting continued
positive uptake of the product overall. Sales growth
in Western Europe (7%) was driven primarily by
­continued uptake for breast cancer and improved
uptake for colorectal and lung cancer. Austerity
measures introduced during the year in Greece,
Spain, Germany and other markets resulted in a progressive
flattening of growth in the region as a ­
whole that was particularly noticeable in the fourth
quarter. Sales in the US were flat for the year, reflecting
reserve adjustments due to the healthcare
reforms enacted in 2010 and regulatory and reimbursement
uncertainty regarding the metastatic
breast cancer indication (see p. 37); together these
factors led to a decline in sales in the second
­half-year, especially the fourth quarter. Avastin maintained
its high US market share in its metastatic
colorectal and lung cancer indications. Very strong
sales growth in Japan (51%) was driven by continued
good uptake in colorectal and non-small cell lung
cancer. Very strong growth was also recorded in
Latin America (42%). In the third quarter Avastin ­
was launched in China in its first indication, first-line
treatment of metastatic colorectal cancer; initial
uptake has been very encouraging.
Full-year sales (oncology and autoimmune diseases)
of MabThera/Rituxan (rituximab), for non-Hodgkin’s
lymphoma (NHL), chronic lymphocytic leukemia
(CLL) and rheumatoid arthritis (RA), totalled 6.4 billion
Swiss francs in 2010, an increase of 9% versus
2009. Sustained growth in the oncology segment was
driven by uptake in CLL and continued strong use ­
in NHL in Western Europe and the US. Solid doubledigit
growth in the International region, including
strong gains in key emerging markets, reflects uptake
of the medicine in its NHL indications. The European
rollout of MabThera in a new indication, first-line
maintenance treatment of patients with follicular lymphoma,
commenced in the fourth quarter. Estimated
sales of MabThera/Rituxan in the RA segment
reached the 1 billion Swiss franc mark in 2010 (16%
of the product’s total sales), 17% higher than in
2009. Growth is being driven by increased use in
patients with an inadequate response to one or more
tumour necrosis factor inhibitors and by growing
acceptance of six-month repeat treatment intervals.
Global sales of Herceptin (trastuzumab), for HER2-
positive breast cancer and HER2-positive metastatic
stomach cancer, rose 7% to 5.4 billion Swiss francs
on sustained, solid single-digit growth in the United
States and Western Europe, and double-digit gains ­
in the International region. Herceptin maintained ­
its high market penetration in breast cancer, with ­
sales also benefitting from initial uptake for stomach
­cancer in EU countries and other markets. In addition,
improvements in the quality of HER2 testing ­
are expanding the population of patients eligible for
treatment with Herceptin. In Japan, where Herceptin
has a market share of approximately 90% in its ­
breast cancer indications, a stable sales volume and
revised reimbursement prices from April resulted ­
in a significant decline in sales revenue compared
with 2009.
Xeloda (capecitabine), for colorectal, stomach
and breast cancer, generated total sales of 1.4 billion
Swiss francs, an increase of 17% compared with
2009. Growth was driven primarily by strong gains in
the United States, Japan and China, the product’s

Pharmaceuticals
Roche Business Report 2010
33­
three largest markets. Global sales of Xeloda are
benefitting from a number of new indications,
­including stomach cancer in China, an expanded
metastatic colorectal cancer indication in Japan, ­
and adjuvant 4 colon cancer in Europe, as well as
increased patient share in metastatic breast ­
cancer in the US and EU.
Sales of Tarceva (erlotinib), for advanced lung
and pancreatic cancer, increased 6% to 1.3 billion
Swiss francs, driven mainly by increased use in ­
the second-line non-small cell lung cancer setting.
The main contributions to growth came from the
International region, Japan and the US. Mid-singledigit
growth in the US reflects steady demand in ­
the lung and pancreatic cancer indications and the
impact of government healthcare reforms. Against ­
a background of stable demand, sales in Western
Europe declined slightly, mainly as a result of government-mandated
price reductions and rebates in
­several major markets. Sustained strong sales growth
in Japan (37%) reflects continued market pene­tration
and oncologists’ increasing confidence in the
benefits of treatment with Tarceva.
Virology
Worldwide sales of Pegasys (peginterferon alfa-2a),
for hepatitis B and C, increased 2% to 1.6 billion
Swiss francs in 2010. Flat sales in the United States
and sales decreases in Western Europe, Japan ­
and certain other mature markets were offset by
growth in the International region, especially ­
Asia—Pacific and CEMAI 5 countries. The product’s
market share continued to expand in the main
­European markets, the US and Japan. Global sales
continued to benefit from clinical data reinforcing ­
the superiority of Pegasys over other treatment
options and increased use in hepatitis B. The hepatitis
C market is poised for major expansion, with the
introduction of a new generation of direct-acting
antiviral agents expected from 2011 onwards.
Because Pegasys — the leading pegylated interferon
— is used in most hepatitis treatment development
programmes today, it is expected to become the
backbone of future combination therapies with the
new antivirals (see also p. 51, below).
Following exceptional demand in 2009 due to the
influenza A (H1N1) pandemic, sales of Tamiflu (oseltamivir),
for influenza A and B, totalled 873 million
Swiss francs in 2010, 73% (2.3 billion francs) lower
than in 2009. With government stockpiling orders
largely completed by early 2010 and the influenza A
(H1N1) pandemic passing its peak, sales fell sharply
in the last three quarters. Sales were also affected ­
by relatively mild influenza seasons in both hemispheres
during 2010. Roche remains ready to address
­potential threats posed by influenza and is maintaining
production capacity in cooperation with
­exter­nal manufacturing partners to enable a rapid
response to future significant outbreaks or government
stockpiling orders.
Ophthalmology
US sales of Lucentis (ranibizumab), for wet agerelated
macular degeneration and macular edema
following retinal vein occlusion, rose 27% to ­
1.5 billion Swiss francs. Strong growth throughout
2010 was driven primarily by increases in the ­
total number of patients receiving Lucentis and the
time patients are on treatment. The US launch of
Lucentis for the treatment of macular edema (swelling
in the retina) following retinal vein occlusion
began in late June, and initial uptake is encouraging.
Lucentis was ­discovered by Genentech, which
retains commer­cial rights in the United States.
Novartis has exclusive commercial rights for the ­
rest of the world.
Inflammation and autoimmune disorders
As the global rollout of the novel rheumatoid ­
arthritis medicine Actemra (tocilizumab, known as
RoActemra in the EU) continued, sales in 2010
totalled 397 million Swiss francs, a rise of 177% over
2009. Uptake of Actemra/RoActemra in the EU, ­
the United States and other launch markets remains
very encouraging. Around 60% of US rheumatologists
have already prescribed the medicine. Continued
strong sales growth in Japan reflects increas­-­
ing use of Actemra as a first-line biologic. Chugai
announced in August that the Japanese health
authorities had removed the approval conditions for
Actemra for the rheumatoid arthritis and polyar­ticular-course
juvenile idiopathic arthritis indica­tions.
4 Adjuvant treatment is given after surgical removal of the
tumour to lower the risk of relapse.
5 CEMAI: Central and Eastern Europe, Middle East, Africa,
Central Asia, Indian Subcontinent.

Clinical development — a long process that continues even after market launch
Creating value for patients means
investing skill and resources in a long,
uncertain journey
10,000
molecules
investment
10
molecules
≤ 50
volunteers or patients
Preclinical development
3–6 years
Phase I
1–2 years
Preclinical testing evaluates a drug’s safety profile and pharmacological
effects in the laboratory. Every promising new compound
must pass rigourous preclinical testing before it can be studied in
humans. New drugs usually undergo both in vitro (in test tubes, cell
cultures and isolated organs) and in vivo (animal) testing. Computer
models are playing an increasingly important role in preclinical development.
Data from preclinical tests are essential for determining
whether a drug is safe enough to be administered to people in clinical
trials.
Phase I trials test the safety of
various doses of a new drug. During
phase I trials researchers are
looking at how the drug is absorbed,
distributed and changed (metabolised)
in the body, how it is eliminated,
how long these processes take, and
whether there are any unwanted
effects. These trials involve only a
small number of people — usually
healthy volunteers. In some cases
people whose disease is very
advanced (cancer, for example) may
also participate.

100–1,000 *
patients
2–3
molecules
≤ 500
patients
1–2
molecules
≤ 15 ,000
patients
1
molecule
Phase II Phase III Phase IV
1.5–2 years 3–3.5 (or more) years from market entry on
Phase II trials test the new drug
in people who have the disease it
is designed to treat. The number
of patients in phase II trials is limited
but usually larger than in phase I
studies. In addition to further safety
testing, these trials identify appropriate
dose ranges and test whether
the drug demonstrates clinical efficacy
(proof of concept). Many new
drugs fail in phase II testing.
A new drug moves into phase III
clinical trials only if the phase I
and phase II trial results suggest
it might benefit patients in signficant
ways. Phase III trials compare
the new drug with current treatments
or, in some trials, with a placebo.
Many phase III trials last a long time,
typically a year or more, and may
involve several thousand patients in
several countries.
Phase III trials must include a large
number of patients so that investigators
can evaluate the differences
between types of treatment. Regulatory
agencies normally require results
from phase III trials before approving
a new drug.
Phase IV trials are conducted after
a drug has been approved by regulatory
agencies and launched on
the market. Also known as post-marketing
trials, they are designed to
gather broader, ‘real-world’ experience
with the new drug in routine medical
practice. Phase IV trials generate additional
data on safety and efficacy in
large numbers of patients and in particular
patient subgroups. They can
also provide further information on
how the drug works in comparison or
in combination with other treatments.
Even large phase III trials cannot identify
all potential side effects: this is
another area where phase IV trials provide
essential additional information.
Roche maintains a system of risk
assessment programmes to identify
and evaluate side effects that did not
appear in phase I–III trials.
* Patients per trial; 5–20 (or more) trials.

36­ Roche Business Report 2010 Pharmaceuticals
Further major approvals for
Actemra/RoActemra, Herceptin,
MabThera/Rituxan and
Lucentis.
The decision gives more patients access to Actemra
and follows positive results from a routine post-­
marketing surveillance programme. Actemra/
RoActemra is now available in some 50 countries
worldwide.
Anemia and transplantation
Sales of the renal anemia medication Mircera (me­thoxy
polyethylene glycol-epoetin beta) rose 51% to
255 million Swiss francs. Demand for Mircera, which
is now available in over 100 countries worldwide, ­
is coming mainly from the predialysis segment and
new patient commencements. Combined sales of ­
the Group’s established anemia medicines, Roche’s
NeoRecormon and Chugai’s Epogin (epoetin beta),
declined 15% to 1.3 billion Swiss francs. Roche
­Pharmaceuticals’ overall share of the European anemia
market remained stable despite increasing
biosimilar competition, due mainly to the strong performance
of Mircera in the major EU countries ­
and a robust market share by volume for NeoRecormon
in the renal indication. A 10% decline in sales ­
of Epogin in Japan was due mainly to competition in
the dialysis market and a lower National Health
Insurance reimbursement price, factors which outweighed
increased demand for the medicine in ­
the predialysis segment.
At 1.3 billion Swiss francs for the full year, sales
­revenue from CellCept (mycophenolate mofetil), for
the prevention of solid organ transplant rejection,
remained significant. The sales decrease of 15% was
due primarily to the loss of patent exclusivity in ­
the United States in 2009. The resulting losses to
competition from generic versions were partly offset
by sales growth in Japan and the International
region.
Development highlights —
key marketed products
In 2010 the Pharmaceuticals Division filed 20 major
new marketing applications and gained 18 major
­regulatory approvals (see tables, pp. 38 and 39). The
following summaries present approvals, filings and
major clinical trial results for key marketed products,
by indication.
Actemra/RoActemra
Approvals | In January 2010 the US Food and Drug
Administration (FDA) approved Actemra for ­
the treatment of adult patients with moderately to
severely active rheumatoid arthritis (RA) who ­
have had an inadequate response to one or more
tumour necrosis factor (TNF) inhibitors. Actemra, ­
the first interleukin-6 receptor-inhibiting monoclonal
antibody approved to treat RA, may be used alone ­
or in combination with methotrexate or other disease
modifying antirheumatic drugs. In June the Euro­pean
Commission extended the product’s existing
marketing approval to include treatment with
RoActemra plus methotrexate to reduce the rate of
progression of joint damage and improve physical
function in patients with rheumatoid arthritis. The
new indication, which is based on two-year data from
a global phase III study (LITHE), came just over a
year after the medicine’s initial EU approval, further
reinforcing its value as an effective treatment for ­
RA. In January 2011 the FDA approved Actemra for ­
a similar indication (inhibition and slowing of
­structural joint damage, improvement of physical
function, and achievement of major clinical response
in adults with moderately to severely active RA),
based on a supplemental Biologics License Application
(sBLA) submitted by Genentech in March
2010.
Filings | In October Genentech submitted a second
sBLA to the FDA and Roche submitted an Accelerated
Assessment application to the European
­Medicines Agency (EMA), seeking to extend the
approved indications of Actemra/RoActemra to
include treatment of systemic juvenile idiopathic
arthritis (sJIA). Both applications are based on positive
data from the global phase III TENDER study.
There are currently no approved therapies in the EU
or US for sJIA, a debilitating and difficult-to-treat

Pharmaceuticals
Roche Business Report 2010
37­
disease that affects the whole body and represents
an area of high unmet medical need.
Avastin
Since its initial approval in 2004 in the United States
for advanced colorectal cancer, Avastin has made
anti-angiogenic therapy a fundamental pillar of cancer
treatment. Avastin is approved in many countries ­
for the treatment of advanced stages of colorectal,
breast, non-small cell lung and kidney cancer. It is
also available in the US and 29 other countries for the
treatment of patients with glioblastoma (a type of
brain cancer). Nearly a million patients have been
treated with Avastin so far. More than 1,000 ongoing
Roche-sponsored or -supported, or independently
conducted clinical trials are investigating the use of
Avastin in over 50 tumour types (including colorectal,
breast, non-small cell lung, brain, gastric, ovarian
and others) and different settings (advanced or
early-stage disease).
Breast cancer | In December, following a review
of all relevant data, the European Committee for
Medicinal Products for Human Use (CHMP) supported
the continued first-line use of Avastin in
­combination with paclitaxel chemotherapy, describing
it as a valuable treatment option for patients
­suffering from metastatic breast cancer. Paclitaxel is
the chemotherapy most frequently used and also
most frequently partnered with Avastin to control the
disease. The committee also considered combinations
of Avastin with two other types of chemotherapy,
based on data from the AVADO and RIBBON-1
trials. The CHMP recommended that the combination
with docetaxel be removed from the Avastin label
and that the combination with capecitabine (Xeloda)
not be approved. A decision by the European Commission
on these recommendations is expected early
in 2011. The CHMP opinion does not affect the ­
other approved uses of Avastin in the European Union
for advanced colorectal, kidney and lung cancer.
Also in December the FDA announced a number ­
of regulatory decisions concerning the use of Avastin
for metastatic breast cancer in the US. The most
important of these is the agency’s decision to initiate
the process to withdraw the current conditional
(‘accelerated’) approval for Avastin for first-line
treatment of metastatic breast cancer. Roche and
Genentech have requested a hearing pursuant to ­
the FDA’s ‘Notice of Opportunity for Hearing’. We
believe this would provide an opportunity to present
our views that the data are clinically meaningful ­
and meet the applicable legal and regulatory standards
for continued approval. Until the conclusion ­
of these proceedings, Avastin remains FDA-approved
for use in combination with paclitaxel for metastatic
HER2-negative breast cancer. At the same time the
FDA issued complete responses for all other pending
applications concerning Avastin in metastatic breast
cancer, saying that the applications failed to support
the extension of the proposed indications: for firstline
treatment in combination with docetaxel (based
on AVADO) and in combination with standard chemotherapy
(based on RIBBON-1), and for second-­
line treatment in combination with standard chemotherapy
(based on RIBBON-2). These decisions do
not affect the availability of Avastin for its approved
uses in other types of cancer in the United States.
Approvals | In February the Chinese health authorities
approved Avastin for the treatment of metastatic
colorectal cancer, its first indication in this important
market.
Filings | In December Roche filed an application
with the EU authorities for approval of Avastin ­
as frontline treatment for ovarian cancer, based on
the results of the phase III GOG218 and ICON-7
­trials (see below, Clinical Milestones).
Clinical milestones | Two large phase III trials
involving some 3,400 patients have demonstrated the
potential of Avastin in ovarian cancer. Results from
GOG218 were presented at the annual meeting of the
American Society of Clinical Oncology (ASCO) in
June. The trial met its primary endpoint of extending
progression-free survival (the period a patient ­
lives without the disease getting worse) in women
with previously untreated advanced ovarian cancer.
ICON-7, a further trial with Avastin in ovarian cancer,
reported positive results in early July. The data ­
were presented at the European Society for Medical
Oncology (ESMO) conference in October. In addition
to the EU filing in December, Roche plans to use ­
the results of both trials to support a regulatory application
for this additional indication in the US in 2011.
Clinical trial results led to a number of adjustments ­
in the Avastin development programme in 2010. As

38­ Roche Business Report 2010 Pharmaceuticals
Major regulatory filings in 2010 1
Product
Clinical data supporting
filing Indication and/or dosage form Country
Actemra/ LITHE (2-year data) rheumatoid arthritis, reduction or inhibition of progression
USA
RoActemra
of joint damage and improvement of physical function
ML21753
rheumatoid arthritis signs and symptoms,
China (refiled)
progressive joint damage
TENDER systemic onset juvenile idiopathic arthritis EU, USA
Avastin RIBBON-2 metastatic breast cancer, second-line treatment USA
ICON-7, GOG 218 metastatic ovarian cancer EU
Herceptin ToGA advanced HER2-positive gastric cancer USA, China
Herceptin ToGA advanced HER2-positive gastric cancer Japan
+ Xeloda
MabThera/
Rituxan
PRIMA
advanced follicular lymphoma, first-line maintenance
following induction treatment with MabThera/Rituxan
EU, USA,
Switzerland
plus chemotherapy
RAVE ANCA-associated vasculitis USA
Mircera ML20680 renal anemia China
CORDATUS
correction of symptomatic anemia in adults with chronic EU, Switzerland
(NH20052)
kidney disease who do not yet need dialysis, once-monthly
administration
Tarceva emerging data metastatic non-small cell lung cancer with EGFR-
EU
from clinical trials,
ongoing clinical
experience
activating mutations, first-line treatment
Xeloda NO16968 (XELOXA) adjuvant colon cancer, combination with oxaliplatin Switzerland
data in the public advanced or refractory gastric cancer in patients who
Japan
domain
are not candidates for curative surgery
XELOX (NO16966) metastatic colorectal cancer, combination with oxaliplatin China (refiled)
1 Includes supplemental indications.
phase III trials with Avastin in stomach (AVAGAST)
and prostate (CALGB 90401) cancer did not meet
their primary endpoints of extending overall survival,
Roche has decided not to pursue regulatory filings
for these indications. A phase III programme investigating
the addition of Avastin to standard treatment
with MabThera/Rituxan plus chemotherapy ­
for diffuse large B cell lymphoma, an aggressive ­
form of non-Hodgkin’s lymphoma, was discontinued
after a safety and efficacy analysis showed an unfavourable
benefit–risk assessment. Following evaluation
of phase III data (AVANT), Roche has discontinued
development of Avastin in adjuvant colorectal
cancer. The results and decision on adjuvant colorectal
cancer do not affect the use of Avastin in ­
the metastatic (advanced) colorectal cancer setting,
where the medicine has demonstrated a clinically
meaningful progression-free and overall survival
­benefit in both first- and second-line treatment.
Avastin has shown a positive benefit–risk ratio in
these and all other approved metastatic cancer
­indications.
Herceptin
Approvals | The European Commission approved
Herceptin in combination with chemotherapy for use
in patients with metastatic stomach (gastric) cancer
exhibiting high levels of HER2, in January 2010.
Approvals for the same indication were received in
Switzerland in May and the US in October, following
priority review by the FDA.
Filings | In June the Japanese health authorities
gave priority review status to an application sub­-­

Pharmaceuticals
Roche Business Report 2010
39­
Major regulatory approvals in 2010 1
Product
Clinical data supporting
filing Indication and/or dosage form Country
Actemra/ OPTION, TOWARD, rheumatoid arthritis signs and symptoms
USA
RoActemra RADIATE, AMBITION,
LITHE (6-month data)
LITHE (2-year data) rheumatoid arthritis, reduction or inhibition of progression
of joint damage and improvement of physical function
EU, Switzerland,
USA 2
Avastin AVF 2107, E3200, metastatic colorectal cancer
China
NO16966 (global);
ARTIST (China)
Herceptin ToGA advanced HER2-positive gastric cancer EU, USA, Switzerland
Lucentis CRUISE, BRAVO macular edema following retinal vein occlusion USA
MabThera/ CLL-8 first-line chronic lymphocytic leukemia USA
Rituxan
REACH relapsed or refractory chronic lymphocytic leukemia USA
PRIMA
advanced follicular lymphoma, first-line maintenance
EU, Switzerland
following induction treatment with MabThera/Rituxan plus
chemotherapy
REFLEX
rheumatoid arthritis, inhibition of progression of joint
EU
damage and improvement of physical function
Mircera CORDATUS
correction of symptomatic anemia in adults with
EU, Switzerland
(NH20052)
chronic kidney disease who do not yet need dialysis,
once-monthly administration
Tarceva SATURN non-small cell lung cancer, first-line maintenance after
USA, EU
chemotherapy
Xeloda NO16968 (XELOXA) adjuvant colon cancer, combination with oxaliplatin EU
1 Includes supplemental indications.
2 January 2011.
mitted in March by Chugai, for approval of Herceptin
for advanced HER2-positive stomach cancer. In ­
June Roche submitted an application for approval ­
of the same indication in China.
Clinical milestones | In December patient enrolment
was completed for a phase III study with a new
subcutaneous formulation of Herceptin in women
with HER2-positive breast cancer. Herceptin is currently
given intravenously over 30 to 90 minutes. ­
The innovative subcutaneous formulation, which is
based on Halozyme’s Enhanze technology (see ­
p. 128), is expected to take less than five minutes ­
to administer and may allow patients with HER2-­
positive breast cancer to receive treatment in their
physician’s office or at home, without having to ­
go to a hospital.
Lucentis
Approvals | In June the US Food and Drug Administration
(FDA) approved Lucentis for the treatment ­
of patients with macular edema (swelling in the
­retina) following retinal vein occlusion (RVO). The
approval followed a six-month priority review by ­
the FDA. RVO occurs when blood flow through a retinal
vein becomes blocked, causing swelling (macular
edema) and hemorrhages in the retina, which may
result in blurring or vision loss in all or part of one
eye.
MabThera/Rituxan (oncology)
Approvals | In February the FDA approved Rituxan
combined with fludarabine and cyclophosphamide
chemotherapy for people with either previously
untreated (first-line) or previously treated (relapsed ­

Will it
Disease area Oncology
Indication
Second-line HER2-positive metastatic breast cancer
Trials
EMILIA (TDM4370g / BO21977)
No. of patients 551 (recruited as of December 2010)
No. of study sites 216
No. of countries 22
Jone F., participant in the EMILIA study (T–DM1), Houston

work ?
Wayne C., T–DM1 Medical Director, Genentech, South San Francisco

T–DM1 — an antibody–drug conjugate
Creating value for patients means building
on good treatments to make them even better
1970s
Non-specific chemotherapy
agents
2000
Herceptin (trastuzumab)
— the new standard of
care for HER2-positive
metastatic breast cancer
The future?
ADC targets chemotherapy
specifically
to tumour cells
Points of attack
Cancer cell
Healthy cell
Chemotherapy
Attacks both healthy
and cancerous cells
Trastuzumab + chemo
The monoclonal antibody
trastuzumab specifically
targets HER2-positive
tumour cells
T–DM1
Attacks cancer cells
only, no conventional
chemotherapy burden
DM1
As the first therapeutic antibody targeting a specific cancer-related biomarker
to receive FDA approval, Herceptin (trastuzumab) launched a revolution in the
treatment of breast cancer. We continue to build on that breakthrough with trastuzumab–DM1
(T–DM1), a novel antibody-drug conjugate (ADC) being developed
T–DM1
to treat HER2-positive breast cancer. T–DM1 combines two powerful anticancer
approaches in one medicine. The trastuzumab antibody component
Trastuzumab
blocks the signals that make HER2-positive cancer cells more
aggressive and sends a message to the patient’s immune system
to destroy the cancer cells. It also delivers DM1, a potent chemotherapy
agent, directly to the tumour cells to induce cell death.
Stable linker
T–DM1 may offer patients with HER2-positive breast cancer effective treatment
that spares them the burden and side effects of conventional chemotherapy.
EMILIA is a phase III registration trial comparing single-agent T–DM1 treatment
with combined lapatinib (another HER2-targeted drug) plus capecitabine
(Xeloda) chemotherapy in women with advanced HER2-positive breast cancer.
Further trials are testing T–DM1 in combination with Roche’s pertuzumab,
another next-generation HER-targeting antibody therapy.

Pharmaceuticals
Roche Business Report 2010
43­
or refractory) CD20-positive chronic lymphocytic
leukemia, based on the results of the CLL-8 and
REACH trials. Following regulatory applications by
Roche and Genentech in the first quarter, in Octo-­
ber the European Medicines Agency (EMA)
approved MabThera as maintenance treatment for
people with follicular lymphoma who have re-­
sponded to induction therapy; the FDA is currently
reviewing Genentech’s sBLA for the same indica-­
tion and has set an action date in late January 2011.
Both submissions were based on the results of ­
the PRIMA study, which showed that ­continuing
MabThera/Rituxan for two years (maintenance ­
therapy) in patients who responded to initial treatment
with MabThera/Rituxan plus chemotherapy
nearly doubled progression-free survival, compared
with those who did not receive maintenance ­
treatment.
Clinical milestones | Based on positive results
from a phase Ib study in patients with follicular lymphoma,
in July Roche decided to advance a new
subcuta­ne­ous formulation of MabThera, also based
on ­Halozyme’s Enhanze technology, into phase ­
III development. Subcutaneous administration has
the potential to significantly simplify treatment ­
by shortening administration time to less than ten
minutes and improving patient comfort. A phase ­
III trial is expected to start in the first quarter of 2011.
Positive data from a phase III study of MabThera/
Rituxan in patients with advanced follicular lymphoma
who did not have symptoms (asymptomatic
disease) were presented at the annual meeting ­
of the American Society of Hematology in December.
The study showed that immediate administration ­
of single-agent MabThera/Rituxan as induction therapy
followed by continued (maintenance) treatment
with MabThera/Rituxan delayed the need for chemoor
radiotherapy and extended progression-free
­survival, compared with watchful waiting. These are
the first phase III data to show that initial use ­
of MabThera/Rituxan monotherapy as induction followed
by maintenance can provide clinical benefit ­
for patients with asymptomatic follicular lymphoma, ­
a disease that is commonly treated only when
­symptoms appear (an approach known as ‘watchful
waiting’).
MabThera/Rituxan (inflammation)
Approvals | Roche received regulatory approval
in October for two additions to the existing EU ­
marketing authorisation for MabThera in rheumatoid
arthritis: based primarily on data from the REFLEX
study, the indications were expanded to include
­inhibition of progression of joint damage and im-­
prove­ment of physical function; and information ­
on enhanced treatment responses in seropositive ­
RA patients (see below, Clinical milestones)
was added to the product’s prescribing information.
Filings | In October, based on data from the phase
II/III RAVE study, Genentech and Biogen Idec
­submitted a supplemental Biologics License Application
to the FDA for approval of Rituxan for ANCAassociated
vasculitis, a group of rare, severe, lifethreatening
autoimmune diseases characterised by
inflammation of blood vessels leading to organ
­damage. There are currently no approved therapies
for the condition, and treatment-associated toxicities
are common with the unapproved standard of care,
cyclophosphamide.
Clinical milestones | An analysis of samples from
patients with RA who participated in two phase III
trials was presented at the European League Against
Rheumatism (EULAR) annual congress in June. It
showed that testing for specific blood markers at the
time of diagnosis could have a significant impact ­
on treatment decisions and lead to improved patient
quality of life. Approximately 80% of RA patients ­
have at least one of two characteristic biomarkers
produced by autoreactive B cells — rheumatoid
­factor (RF) and anticyclic citrullinated peptide (anti-
CCP) — in their blood. Such patients are referred
to as ‘seropositive’. Data from a pooled cohort of the
two studies showed that, while both seropositive ­
and seronegative patients benefitted from treatment
with MabThera/Rituxan, the response was enhanced
in the seropositive population. Additional biomarker
analyses from other phase III studies are pending.
MabThera/Rituxan is the first and only selective B cell
targeted therapy available for RA.
Tarceva
Approvals | In April the US Food and Drug Administration
(FDA) approved Tarceva as a maintenance
treatment for patients with locally advanced or metastatic
non-small cell lung cancer (NSCLC) whose

44­ Roche Business Report 2010 Pharmaceuticals
Roche has 12 innovative new
molecular entities in late-stage
development, including six
potential personalised healthcare
medicines with planned
companion diagnostic tests.
disease has not progressed after four cycles of
­platinum-based first-line chemotherapy. In April the
European Commission approved Tarceva as monotherapy
for maintenance treatment in patients with
advanced non-small cell lung cancer (NSCLC)
whose disease remains largely unchanged (known ­
as stable disease) after platinum-based initial
­chemotherapy. Both approvals are based on data
from the phase III SATURN study, which showed
that, compared with placebo, Tarceva significantly
improved overall survival in patients with stable
­disease. Patients with advanced NSCLC and stable
disease after initial chemotherapy have tumours ­
that progress faster, are more resistant to further
lines of chemotherapy and have a poorer prognosis
compared with patients who have a complete or ­
partial response to initial chemotherapy.
Filings | In June Roche submitted an application to
the European Medicines Agency (EMA) to extend
the current marketing approval for Tarceva to include
first-line treatment of patients with advanced NSCLC
with EGFR-activating mutations. The application ­
is supported by emerging data from clinical trials and
ongoing clinical experience, including new data ­
from the OPTIMAL trial presented at ESMO (see
below). Tarceva is the only epidermal growth factor
receptor (EGFR) inhibitor approved for use in
­maintenance and second-line treatment settings ­
in patients with advanced or metastatic NSCLC, ­
irrespective of the presence of EGFR-activating
mutations. A licence for Tarceva for use in the firstline
setting would allow physicians to personalise
early treatment according to EGFR activating mutation
status, while people with NSCLC without
EGFR-activating mutations would continue to benefit
from treatment with Tarceva in later lines of therapy.
Clinical milestones | Results from a randomised
phase III study (OPTIMAL) presented at the
­European Society for Medical Oncology (ESMO)
congress in October demonstrated that first-line
treatment with Tarceva extended progression-­
free survival in patients with advanced NSCLC with
EGFR-activating mutations to more than one year,
almost three times longer than patients who received
conventional chemotherapy. Interim results from ­
a second trial investigating Tarceva in this indication
(EURTAC) are expected in the first quarter of 2011.
As many as 30% of Asian patients with lung cancer
and an estimated 10% of lung cancer patients in
Western countries have this distinct form of NSCLC.
Xeloda
Approvals | In March the EU authorities approved
Xeloda in combination with oxaliplatin (a com­-­
bin­ation known as XELOX) for the adjuvant (postsurgical)
treatment of patients with early colon
­cancer. The approval was based on results from ­
the NO16968 (XELOXA) study, one of the largest ­
studies of patients with stage III (early) colon cancer,
which showed that patients taking XELOX immediately
after surgery lived disease-free for longer
­compared with those treated with a chemotherapy
regimen consisting of 5-fluorouracil plus leucovorin.
Filings | In Japan Chugai filed marketing applications
with the Ministry for Health, Labour and ­
Welfare in March for approval of Xeloda combined
with ­Herceptin for the treatment of advanced ­
HER2-positive stomach cancer and in September ­
for Xeloda in advanced or refractory gastric
­(stomach) cancer in patients who are not candi­-­
dates for ­curative surgery.
Clinical milestones | A data analysis completed
in June showed that NO17629, a phase III trial investigating
Xeloda in combination with docetaxel for ­
the adjuvant (postsurgical) treatment of women with
early breast cancer, did not meet its primary endpoint
of extending disease-free survival but did meet
the secondary endpoint of extending overall sur­vival.
Roche has decided not to pursue regulatory
­filings for this indication.

Pharmaceuticals
Roche Business Report 2010
45­
Research and development
Roche’s Pharmaceuticals Division is committed ­
to discovering and commercialising innovative medicines
that represent true medical value in areas ­
of high unmet need. To ensure a strong flow of suitable
candidate molecules into its development pipeline,
Roche has built a unique innovation network of
independent research and development centres. In
addition to Roche and Genentech, it includes Chugai
in Japan and alliances with more than 150 partner
organisations worldwide. This promotes a diversity ­
of research approaches and enables access to new
technologies and promising drug candidates.
Close cooperation between the Pharmaceuticals
Division and Roche Diagnostics is a key strategic
advantage for our company. It ensures that diagnostics
expertise is seamlessly integrated into all partsof
the pharmaceutical R & D process. This is central
to Roche’s goal of advancing personalised healthcare
(PHC), an approach that seeks to tailor treatments ­
to specific patient subpopulations based on growing
scientific understanding of biology and disease at ­
the molecular level.
Two recent examples of the progress that Roche is
making towards PHC in the development of therapies
for difficult-to-treat diseases are RG3638 (MetMAb)
for lung cancer and RG7204 (BRAF inhibitor) for
malignant melanoma. Roche Diagnostics is developing
diagnostic tests designed to guide appropriate
use of both compounds in their target patient populations.
Roche’s research on antibody–drug conjugates
as a means of treating cancer is another
­example of a highly targeted approach with the
potential of improving outcomes while reducing ­
the side ­effects of treatment. T–DM1, for HER2-­
positive breast cancer, is the most advanced ­
of these projects. For more information, see below,
Oncology, and also pp. 18 and 19 of this report.
As part of the Group’s Operational Excellence programme,
the Pharmaceuticals Division is prioritising
its R & D investments in order to dedicate resources
to projects with the highest potential. Following ­
a comprehensive portfolio review, Roche decided to
discontinue R & D activities in RNA interference,
­consolidate internal functional resources and reduce
the number of Pharma Research and Early Development
sites from 11 to seven, thereby reducing
fixed costs and making funds available for additional
external research partnerships and promising new
programmes entering phase II clinical development.
At the beginning of 2011 the division’s R & D pipe-­
line included 102 projects in clinical development ­
(phase I to III and filed for regulatory review). Of
these, 62 involved new molecular entities (NMEs)
and 40 involved additional indications. Twelve ­
NMEs are in late-stage development (see table, ­
p. 47). Twenty-two projects investigating additional
indications for existing products are in phase III. ­
The Pharmaceuticals pipeline is shown in the fold-out
inside the front cover of this report. Further details
are available at www.roche.com.
Roche and Genentech — 376 projects
in research and early development
(discovery, phases 0–II) | January 2011
Roche and Genentech — 39 projects
in phase III (or marketing applications
filed) | January 2011
Inflammation 65
Metabolic 29
Others 12
Ophthalmology 3
Virology 65
Oncology 26
Metabolic 2
CNS 3
Ophthalmology 2
Inflammation 6
CNS 63
Oncology 139

46­ Roche Business Report 2010 Pharmaceuticals
Four additional NMEs advance
into late-stage development:
MetMAb (lung cancer), lebrikizumab
(asthma), RG7128
(hepatitis C), ocrelizumab (MS).
Oncology
Roche’s clinical development pipeline in oncology
includes 29 new molecular entities. The Pharmaceuticals
Division is further strengthening its oncology
portfolio through new targeted therapeutic
options and expanding into new indications. Six
oncology NMEs are now in late-stage clinical testing.
Pertuzumab (RG1273) is a HER2 dimerisation inhi­bitor
that is being studied with the current standard ­
of care, Herceptin plus chemotherapy, in HER2-­
positive breast cancer. Data from a phase II trial
(NEOSPHERE) investigating pertuzumab and
­Herceptin plus docetaxel chemotherapy in HER2-
positive early breast cancer were presented at ­
the San Antonio Breast Cancer Symposium in De-­
cem­ber. The results showed that the two antibodies
plus docetaxel given in the neoadjuvant setting
(before surgery) improved the rate of complete
tumour ­disappearance in the breast by more than
half compared with Herceptin plus docetaxel chemotherapy.
Based on the encouraging efficacy results
from NEOSPHERE, pertuzumab will also be studied
as adjuvant (postsurgical) therapy in HER2-positive
early breast cancer. The phase III clinical programme
in this setting is scheduled to start in late 2011.
Results and related regulatory filings are expected ­
in 2011 from a phase III study (CLEOPATRA) evaluating
the addition of pertuzumab to Herceptin and
chemotherapy in the first-line treatment of patients
with advanced (metastatic) disease.
Trastuzumab–DM1 (T–DM1, RG3502) is a novel
anti­body–drug conjugate that combines the therapeutic
effect of trastuzumab (the active substance ­
of ­Herceptin) with intracellular delivery of DM1, ­
a highly potent chemotherapy agent, to specifically
target HER2-positive tumours (see p. 42). Data from ­
a randomised phase II trial (TDM4450g) with T–DM1
in previously untreated HER2-positive metastatic
breast cancer presented at the ESMO conference in
October showed efficacy comparable to Herceptin
plus chemotherapy, the standard of care, along with
a significantly reduced side effect burden. Final
results from this study are expected in 2011.
Two phase III registration studies in metastatic
HER2-­positive breast cancer are ongoing, and we
plan to submit global marketing applications in ­
2012. EMILIA, investigating T–DM1 in pretreated
patients, is expected to yield data on progressionfree
survival in 2012 and overall survival in 2013.
MARIANNE, a comparative trial of first-line treatment
with either T–DM1 alone or T–DM1 plus
­pertuzumab versus Herceptin plus chemotherapy,
began in July. Both trials are investigating therapeu-­
tic options that target HER2-positive tumours ­
while sparing patients the burden and side effects ­
of conventional chemotherapy.
RG7204 (PLX4032, collaboration with Plexxikon)
is a first-in-class molecule designed to selectively
inhibit a cancer-causing, mutated form of the BRAF
protein found in approximately half of metastatic
melanoma tumours. Promising results from a phase ­
II clinical trial (BRIM2) were presented in November ­
at the International Melanoma Research Congress.
The data showed that RG7204 shrank tumours ­
in over half of patients with previously treated BRAF
V600E mutation-positive metastatic melanoma.
Median progression-free survival in the study was
6.2 months. Typically, progression-free survival for
these patients is approximately two months. A phase
III trial (BRIM3) in previously untreated BRAF
­mutation-positive metastatic melanoma patients met
its primary endpoints in January 2011, with an ­
interim analysis showing significantly improved overall
and progression-free survival in patients who
received RG7204 compared with those treated with
dacarbazine, the current standard of care. Roche
Molecular Diagnostics is developing a companion
diagnostic, cobas 4800 BRAF V600 Mutation ­
Test (see pp. 59, 69, 78), to identify patients whose
tumours carry the abnormal BRAF gene and are
therefore appropriate for treatment with RG7204.

Pharmaceuticals
Roche Business Report 2010
47­
Twelve new molecular entities in ongoing or planned late-stage studies
Compound Indication Status Expected first filing
pertuzumab HER2-positive metastatic phase III started in 2008 2011
breast cancer, first line
trastuzumab–DM1 HER2-positive metastatic phase III started in first quarter 2009 2012
breast cancer, first and
second line
RG7204 (BRAF
inhibitor)
metastatic melanoma phase III trial in first-line treatment met primary
endpoints in January 2011
2011
RG3616 (hedgehog
pathway inhibitor)
RG7159 (GA101)
advanced basal cell
carcinoma
pivotal phase II started in first quarter 2009 2011
chronic lymphocytic phase III started in fourth quarter 2009
2013
leukemia, non-Hodgkin’s (chronic lymphocytic leukemia)
lymphoma
RG3638 (MetMAb) solid tumours LIP 1 decision made, preparing for phase III post-2013
lebrikizumab asthma LIP 1 decision made, preparing for phase III post-2013
aleglitazar cardiovascular risk reduction
phase III initiated in first quarter 2010
post-2013
in type 2 diabetes
dalcetrapib dyslipidemia, cardiovascular
phase III enrolment completed in second quarter
2013
high risk 2010
RG7128 (HCV polymerase
hepatitis C LIP 1 decision made, preparing for phase III 2013
inhibitor)
RG1678 (glycine negative symptoms of phase III started November 2010 2013
reuptake inhibitor) schizophrenia, suboptimally
controlled positive
symptoms of schizophrenia
ocrelizumab multiple sclerosis phase III planned to start in first quarter (PPMS) post-2013
(RRMS and PPMS) and second quarter (RRMS) 2011
1 Lifecycle investment point (decision to commence late-stage development leading to submission of marketing applications).
RG3616 (GDC-0499; collaboration with Curis) is
a novel compound targeting the hedgehog signalling
pathway, which is thought to be implicated in
­sev­eral cancers. A pivotal phase II study with registration
potential is currently investigating RG3616
as a potential treatment for advanced basal cell
­carcinoma (BCC). RG3616 is also being evaluated ­
in a phase II study as a therapy for operable BCC. ­
In the fourth quarter Roche decided to discontinue
development of the compound in ovarian and colorectal
cancer due to lack of benefit in phase II trials.
RG7159 (GA101) is the first type II, glycoengineered,
anti-CD20 monoclonal antibody being investigated ­
in late-stage clinical trials as a potential treatment for
non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic
leukemia (CLL). It has been specifically
designed to enhance the destruction of cancerous B
cells by activating other immune cells to attack ­
the cancer cells and by inducing direct cell death. ­
In two phase II studies presented at the American
­Society of Hematology annual meeting in Decem-­
ber, treatment with RG7159 produced promising
response rates in very difficult-to-treat patients with
either indolent or aggressive NHL who had not
responded to multiple prior treatments, including
MabThera/Rituxan. Further clinical data for RG7159
in NHL and CLL are expected in 2011. Phase III
studies of RG7159 versus MabThera/Rituxan in
aggressive and indolent NHL are scheduled to start
in 2011.
RG3638 (MetMAb) is a unique monoclonal antibody
that binds specifically to the c-Met protein receptor.
The Met pathway can be inappropriately activated ­
in cancer and lead to invasive growth. New phase II

What are the
Disease area Metabolic and cardiovascular diseases
Indication
CV risk reduction in patients with type 2 diabetes
Trials
ALECARDIO
No. of patients 6,000
No. of study sites 750
No. of countries 24
Ragnar B., participant in the ALECARDIO (aleglitazar) trial, Stockholm

implications ?
Anita M.-W., Operations Program Leader, Roche Basel

Aleglitazar
Creating value for patients means focusing
on the unsolved issues
For patients with type 2 diabetes (T2D), blood glucose
control is no longer the biggest concern. More than 60%
of patients with diabetes die from heart disease and
stroke, not from an inability to control blood glucose.
And 10% of patients who experience an acute coronary
syndrome (ACS) event, such as a heart attack, die within
one year. Currently, there are no drugs on the market
that specifically and effectively control their high risk of
cardiovascular disease.
Aleglitazar, a dual PPAR α/γ co-agonist developed
at Roche, may become the first compound with the
potential to reduce cardiovascular morbidity and
mortality specifically in high-risk patients with T2D.
Aleglitazar is an excellent example of translational
medicine: biochemical parameters, animal data,
and biomarkers of efficacy and safety consistently
supported hypotheses that were later proven in
clinical settings.
Increased risk of heart attack and stroke
associated with T2D
Healthy people
People who have had a
heart attack or stroke
ALECARDIO, an innovative global, randomised,
controlled phase III clinical trial with some 6,000
patients, is now testing the hypothesis that aleglitazar
can reduce cardiovascular morbidity and
mortality in patients with T2D who have suffered
a recent ACS event.
People with T2D
People with T2D who
have had a heart attack
or stroke
Risk
Demonstrating the multiple effects of aleglitazar
Conventional trial in people with T2D
1–2 years
Reduction of
blood glucose
levels
5 years
Trial with aleglitazar in T2D high-risk subpopulation
Blood glucose Blood fats Hypertension
Focused on reducing
cardiovascular risk
in people with type 2 diabetes
Saving lives

Pharmaceuticals
Roche Business Report 2010
51­
data presented at the annual European Society for
Medical Oncology (ESMO) conference in October
showed a significant increase in progression-free
survival for patients with high Met-expressing nonsmall
cell lung cancer (NSCLC) who were treated
with MetMAb plus Tarceva. Based on this data, in
September Roche advanced the compound into latestage
development for the second- and third-line
treatment of NSCLC. A phase III study in patients
with high Met-expressing NSCLC is expected to
start in 2011. Roche Tissue Diagnostics is developing
a companion diagnostic test to identify patients ­
with high Met-expressing NSCLC who are most likely
to respond to treatment with RG3638 (see pp. 19,
59, 74). A phase II study to investigate the addition
of MetMAb to chemotherapy, with or without Avastin,
for the treatment of triple negative metastatic breast
cancer is expected to enrol its first patient in the ­
first quarter of 2011.
Inflammation and autoimmune disorders
Roche has eight new compounds in development ­
for chronic and progressive autoimmune and inflammatory
diseases such as rheumatoid arthritis (RA)
and asthma, five of which are in phase II clinical testing.
Lebrikizumab is a humanised monoclonal antibody
designed to bind specifically to interleukin-13,
a protein thought to play a key role in the airway
inflammation, hyperresponsiveness and obstruction
experienced by asthma patients. The compound ­
is being developed for the treatment of moderate to
severe persistent asthma. Patient recruitment for ­
two key phase II trials (MOLLY and MILLY) has been
completed. Based on promising phase II results with
lebrikizumab in patients whose symptoms remained
uncontrolled on inhaled corticosteroids, with or
­without a second controller, Roche has decided to
advance the molecule into late-stage clinical testing.
In May Roche and Biogen Idec announced their
decision to discontinue development of ocrelizumab
(RG1594) for rheumatoid arthritis (RA). Following ­
a detailed analysis of the efficacy and safety results
from the RA programme, the companies concluded
that the overall benefit–risk profile of ocrelizumab
was not favourable in RA, taking into account
­currently available treatment options, including
MabThera/Rituxan. Development of ocrelizumab ­
as a therapy for multiple sclerosis is continuing ­
(see p. 52).
Metabolic and cardiovascular diseases
Roche has nine new compounds in development for
metabolic and cardiovascular diseases. ­Dalcetrapib
(RG1658, JTT-705; licensed from Japan Tobacco) is ­
a novel cholesteryl ester transfer protein (CETP)
modulator being tested for its ability to reduce cardiovascular
events in patients with ­stable coronary
heart disease following a recent acute coronary syndrome
event. The phase III dal-HEART programme ­
is on track: recruitment for the phase III dal-OUT-
COMES trial has been completed, with over 15,600
participants enrolled. Results from two phase IIb
studies (dal-VESSEL and dal-PLAQUE) are expected
in 2011, and recruitment for a further phase III study
(dal-PLAQUE 2) is ongoing. These supporting studies
are investigating the potential impact of dalcetrapib
treatment on atherosclerotic plaque burden, using
imaging techniques and functional tests.
Aleglitazar (RG1439) is an innovative investigational
treatment designed to reduce the incidence and
impact of cardiovascular mortality, non-fatal heart
attack and stroke in patients with a recent acute coronary
syndrome and type 2 diabetes. A global phase
III programme (ALECARDIO) began recruitment
early in 2010. Aleglitazar has the potential to be the
first therapy to specifically reduce cardiovascular ­
risk in people with type 2 diabetes.
Taspoglutide (RG1583, BIM51077; licensed from
Ipsen) is a once-weekly human glucagon-like peptide-1
(GLP-1) hormone analogue in development ­
for the treatment of type 2 diabetes. In September
Roche communicated its decision to stop administering
taspoglutide to patients in global phase III
­clinical trials, based on higher than expected patient
discontinuation rates observed in analyses of data
from the T-emerge programme, and also due to ­
the antibody-monitoring plan implemented to address
serious hypersensitivity reactions. After careful
assessment of the relevance of the T-emerge safety
and efficacy data to support future regulatory
approval in type 2 diabetes, including consideration
of the current portfolio evaluation initiative, ­
Roche has decided to discontinue the taspoglutide
T-emerge development programme.

52­ Roche Business Report 2010 Pharmaceuticals
As the first in a new class of
medicines, RG1678 has the
potential to redefine the therapeutic
approach to a range
of psychiatric disorders.
Virology
Roche currently has two direct-acting antiviral agents
in late-stage development for hepatitis C: the nucleoside
polymerase inhibitor RG7128 (partnered with
Pharmasset) and the protease inhibitor danoprevir
(RG7227). Both of these oral agents are being investigated
in combination with Pegasys and ribavirin,
and in combination with each other in an interferonfree
regimen. RG7128 interim phase IIb results
showed good efficacy and tolerability, with no evidence
of viral resistance after three months’ therapy
in combination with Pegasys and ribavirin. A phase I
trial (INFORM-1) of RG7128 and danoprevir as an
interferon-free combination showed significant viral
suppression. A phase III programme with RG7128 ­
is expected to begin in 2011. In October 2010 Roche
acquired the global rights to danoprevir, to increase
the strategic flexibility of the Group’s hepatitis C
portfolio.
there are currently no approved treatments. The ­
first of six planned trials began in November 2010.
As the first in a new class of medicines, RG1678 ­
has the potential to redefine the therapeutic
approach to a range of psychiatric disorders and
deliver clinical benefits beyond those achievable ­
with current treatment options.
In October Roche and Biogen Idec reported posi­-­
tive results from a phase II trial with the humanised
anti-CD20 monoclonal antibody ocrelizumab
(RG1594) in patients with relapsing-remitting multiple
sclerosis (RRMS), one of the leading causes ­
of neurological disability in young adults. Data presented
at the annual meeting of the European
­Committee for Treatment and Research in Multiple
Sclerosis (ECTRIMS) showed that, compared with
placebo, ocrelizumab significantly reduced signs of
disease activity, as measured by brain lesions and
annualised relapse rate, with no opportunistic infections
reported. Two phase III ­studies will begin in the
­second quarter of 2011 to explore the drug’s efficacy
in RRMS compared with interferon, the current
standard of care. A phase III study investigating the
potential of ocrelizumab in patients with primary
­progressive multiple sclerosis (PPMS) is planned to
start in the first quarter of 2011. In October Genentech
and Biogen Idec amended their collaboration on
antibodies targeting CD20 and agreed that Genentech
will have respon­sibility for the further development
of ocrelizumab in multiple sclerosis in the US.
Central nervous system
The Roche portfolio has 10 novel compounds in
development for disorders of the central nervous system,
including schizophrenia, multiple sclerosis and
other serious conditions. One of these compounds is
RG1678, a novel glycine reuptake inhibitor being
developed for the treatment of schizophrenia, an area
of high unmet medical need. Promising data from ­
a phase II proof-of-concept study with RG1678 in
patients with negative symptoms of schizophrenia
were presented at the annual meeting of the American
College of Neuropsychopharmacology in
December. A global phase III programme has been
initiated to investigate RG1678 in combination ­
with antipsychotics in patients with either negative
symptoms or suboptimally controlled positive
­symptoms of schizophrenia, indications for which

Pharmaceuticals
Roche Business Report 2010
53­
Focus on unmet medical
needs
Cancer | According to the latest International
Agency for Research on Cancer (IARC) estimate, in
2008 over 12 million people worldwide were diagnosed
with cancer, and some 7.6 million died of the
disease. The IARC anticipated then that cancer
would surpass heart disease as the leading cause ­
of death worldwide in 2010. The agency also forecasts
that by 2030 there will be over 26 million new
cases and 17 million deaths per year from cancer. ­
In Europe alone, one in three people can expect to
develop cancer in their lifetime. Cancer is not one
disease but a group of more than 100 distinct disorders,
each with its own medical challenges.
Non-Hodgkin’s lymphoma | A group of over 30
cancers that affect the lymphatic system. This class
of cancer currently affects over 1.5 million people
worldwide, and some 350,000 new diagnoses ­
are made each year. Follicular lymphoma accounts
for about one in four of all cases of non-Hodgkin’s
lymphoma. It can occur at any time during adulthood,
though people are typically diagnosed during their
sixties, and it affects as many men as it does women.
Chronic lymphocytic leukemia | The most common
type of leukemia in adults, accounting for 25–30% ­
of all forms of leukemia. The incidence of CLL in
Western countries is approximately 3 per 100,000,
and it is twice as common in men as in women.
Colorectal cancer | Cancer of the large intestine
or rectum, which accounts for over 1 million new
cases (around 10% of all newly diagnosed cancers)
worldwide each year. It is the second most common
cause of cancer deaths in Europe and the third ­
most common worldwide.
Breast cancer | The most common cancer among
women worldwide. Over 1.4 million women are newly
diagnosed and over 450,000 die from the disease
each year. As there are several different types of
breast cancer, knowledge of tumour characteristics
is important for treatment decisions. Some 15–25%
of women with breast cancer have tumours with
abnormally high levels of a protein known as HER2.
HER2-positive tumours are particularly aggressive,
fast-growing and likely to recur.
Lung cancer | The most common form of cancer
worldwide 6 and the leading cause of cancer deaths.
There are an estimated 1.4 million new cases annually.
Non-small cell lung cancer is the most common ­
form, accounting for approximately 80% of all cases.
Malignant melanoma | The deadliest and most
aggressive form of skin cancer. The life expectancy
of people with advanced melanoma is usually ­
short, with less than one in four expected to be ­
alive one year after diagnosis. Every year an
­estimated 40,000 people worldwide die from the
­disease; the number of new cases in developed
countries is expected to double, to 227,000 per year,
by 2019. Approximately 50% of melanomas carry
activating mutations in the BRAF protein, a key component
of the RAS–RAF signalling pathway involved
in normal cell growth and survival. These mutations
cause the pathway to be overactive, which may ­
lead to excessive growth and cancer. It is estimated
that approximately 8% of all solid tumours carry
BRAF V600 mutations.
Pancreatic cancer | A particularly aggressive disease
that is extremely difficult to treat. It kills a higher
proportion of patients in the first year after diagnosis
than any other cancer. The fifth leading cause of
cancer deaths in the developed world, pancreatic
cancer claims nearly 80,000 lives every year.
Kidney cancer | This type of cancer is newly diagnosed
in around 200,000 people and causes 100,000
deaths worldwide every year, rates that are expected
to increase. Renal cell carcinoma accounts for 90%
of all kidney cancers.
6 Excluding non-melanoma skin cancers, most of which are easily
treated and not life-threatening.

54­ Roche Business Report 2010 Pharmaceuticals
Gastric (stomach) cancer | Stomach cancer is the
second most common cause of cancer-related
deaths in the world and the fourth most commonly
diagnosed cancer. It accounts for over 1 million ­
new cases and some 800,000 deaths each year. The
vast majority of cases occur in Asia, where, with ­
lung cancer, it is the leading malignancy. Advanced
(metastatic) stomach cancer is associated with a
poor prognosis: the median survival time after diagnosis
is 10–11 months with currently available therapies.
Early diagnosis of this disease is challenging
because most patients with early-stage disease do
not show symptoms.
Age-related macular degeneration (AMD) | A
major cause of gradual or sudden, painless, central
visual loss in the elderly and a leading cause of ­
vision loss in people aged 60 and older. There are
two forms of AMD — wet and dry. All cases begin
as the dry form, but 10–15% progress to the wet
form, which can result in sudden and severe central
vision loss. In wet AMD, new blood vessels grow
under the retina and leak blood and fluid, causing
deterioration of the macula, the portion of the ­
eye responsible for fine, detailed central vision. More
than 1.7 million Americans have the advanced form ­
of this condition.
Anemia | Occurs when the number of red blood
cells or the hemoglobin molecules they contain ­
falls below normal, resulting in insufficient oxygen
reaching organs and tissues. It is seen in up to ­
80% of patients with chronic kidney (renal) disease,
which affects more than 500 million people worldwide.
In addition, anemia affects three out of four
cancer patients undergoing chemotherapy. Patients
with untreated anemia may need blood transfusions.
The potential long-term effects of anemia include
cardiovascular disease in renal patients, while in
patients with cancer it is associated with diminished
quality of life.
Hepatitis B and C | The hepatitis B and C viruses
(HBV, HCV), which are commonly transmitted
through blood-to-blood contact, cause acute and
chronic liver disease, potentially leading to liver
­failure, cirrhosis liver cancer, and death. Worldwide,
350 million people are thought to be chronically
infected with HBV, a highly infectious virus that is
responsible for an estimated one million deaths
annually. More than 170 million people around the
world are infected with HCV, and three to four ­
million new cases occur each year. Hepatitis C is ­
the main reason for liver transplantation. A recent
study on the HCV-related burden of disease in ­
22 European countries estimated that between seven
and nine million people, or over 1% of the popula­tion,
are infected with HCV.
Autoimmune disorders | Occur as a result of a mistaken
immune response to the body’s own tissues.
The causes are unknown. Rheumatoid arthritis, multiple
sclerosis and lupus erythematosus are among ­
the most common autoimmune disorders, which affect
millions of people worldwide.
Rheumatoid arthritis (RA) | An autoimmune disease
characterised by inflammation that leads to stiff,
swollen and painful joints, ultimately resulting in
­irreversible joint damage and disability. More than ­
20 million people worldwide and twice as many
women as men suffer from RA. In addition to inflammation
of the joints, such as the hands, feet and
wrists, RA can cause fatigue, heart disease and
increase the likelihood of developing other complications
such as osteoporosis, anemia, and problems
with the lungs and eyes. It can shorten life expectancy
by 6–10 years. B cells (a type of immune cell)
are known to play a key role in the inflammation
associated with RA. Several key cytokines, or proteins,
are also involved, including interleukin-6 (IL-6), TNF
alfa and interleukin-1 (IL-1). IL-6 has been identified
as having a pivotal role in the ­inflammation process.

Pharmaceuticals
Roche Business Report 2010
55­
Multiple sclerosis (MS) | An often debilitating
autoimmune disease in which nerve impulses passing
through the central nervous system are disrupted
due to damage to the brain and spinal chord. This
leads to unpredictable and highly variable symptoms
ranging from abnormal sensations and reduced coordination
to pain, paralysis, visual impairment and a
decline in cognitive and other functions. According
to WHO estimates, approximately 1.3 million people
worldwide are living with the disorder, which is
­usually diagnosed in adults aged between 20 and ­
40 years. Relapsing-remitting multiple sclerosis
(RRMS), the most common form, is characterised by
acute exacerbations with full or partial recovery
between attacks. Primary progressive multiple sclerosis
(PPMS) is characterised by neurological
­disability from onset, with symptoms gradually worsening
over time.
Diabetes | Recognised as a global epidemic by
the World Health Organization. The International ­
Diabetes Federation estimates that some 360 million
people worldwide will have diabetes by 2030.
According to the WHO, type 2 (adult onset) diabetes
accounts for around 90% of all cases. Uncontrolled
type 2 ­diabetes can lead to severe complications
such as cardiovascular disease, stroke, blindness,
amputations, and kidney failure, resulting in significant
healthcare burdens to society.
Schizophrenia | A severe mental disorder that
­distorts the way a person thinks, acts, expresses
emotions, perceives reality and relates to others.
According to WHO estimates, schizophrenia affects
approximately 24 million people worldwide and is
usually diagnosed in adults aged between 15 and 35
years. The symptoms of schizophrenia are broadly
categorised as positive, negative and cognitive. Positive
symptoms are psychotic behaviours such as ­
hallucinations and delusions. Negative symptoms
include apathy, social withdrawal, lack of drive ­
and reduced ability to feel pleasure in everyday life.
Cognitive deficits include difficulty concentrating ­
or following instructions, difficulty completing tasks,
memory problems, and disorganised thinking.
­Persistent negative symptoms are a major cause of
burden for patients and caregivers.
Glossary
Adjuvant treatment | Treatment given after surgical
removal of a tumour to lower the risk of relapse.
Disease-free survival | The length of time after
treatment for a specific disease during which ­
a patient survives with no sign of the disease.
First-line treatment | The initial treatment given
after diagnosis, including the first treatment ­
given after metastatic cancer has been diagnosed.
Maintenance treatment | Treatment given to­ prevent
a disease getting worse or to prevent a cancer
from recurring when it has disappeared following
­initial therapy.
Metastatic disease | Cancer that has spread
from the original site of a tumour to other parts of ­
the body. Also referred to as advanced disease.
Neoadjuvant treatment | Treatment given to
reduce the size of a tumour before surgical removal ­
is attempted.
Overall survival | The time from the start of
­treatment until the patient dies.
Progression-free survival | The length of time
­during and after treatment during which a patient
lives without the disease getting worse.
Second-line treatment | Treatment given if the
­initial, or first-line, treatment does not work, or if ­
the cancer stops responding to it.