Transcript Diapositive 1 - Moodle Lille 2

Mohammed BOUZID
Mohamed GHANEM
Youcef DEHBI
ABOUT GILEAD
US biopharmarceutical company
HQ in Foster City, California
Founded in 1987 by Dr MICHAEL RIORDAN under
the name of “OLIGOGEN”
Named after “the balm of Gilead “
Completed its IPO in 1991
Michael L. Riordan
Gilead’s primary areas of focus include : viral, cardiovascular and
respiratory diseases
More Than 2,800 Employees around the World
ANTISENSE :
GILEAD’S FIRST STEP
Research were centered on what were known as "anti-sense" drugs
RNAm
d
e
s
e
a
s
e
Antisense
Affinity ?
Traditional drug
A « propyne group »was added to bases of nucleotids
Binding affinity increased by 10 to 100 times
but
Several problems had to be resolved before making antisense work as
drug
PROBLEMS MET
MUTAGENIC
EFFECTS
ELECTRICAL
CHARGE
ANTISENSE
SHORT
TERM
TOXICITY
SIZE
• Partnership with Glaxo holdings plc to develop genetic code-blockers for
cancer’s treatment ($8 million).
• Dr John Martin a specialist in nucleic acid chemistry was recruited by Gilead
“came from BMS”
After several years of research:
A strong expertise in nucleic acid chemistry was established
The company was not closer to marketable product.
Gilead will need an other alternative!
Second step:
From antisense to antivirals
How it began ?
•Bristol-Myers merged with Squibb in 1989 and cut back on HIV spending.
•Martin went back to Bristol-Myers library returned to its european inventors
•In 1991, Gilead licensed rights to the anti-viral drug candidates .
•Research were redirected to antivirals and antisense program was abandoned later
Three marketed products:vistide;Hepsera;viread
All patents of Antisens chemistry were sold to ISIS pharmaceutical for $6M(1998)
Gilead’s objectives
Keeping its focus on antivirals
To Favour collaboration and partnerships
To growth through acquisitions
Reducing dvpt costs and commercialisation timeline
Satisfy the unmet medical need
Acquisitions
REQUIRMENTS & REQUISES
NEXSTAR PHARMACEUTICAL
Acquisition in July,1999 for $550 MILLION
Selex intellectual rights licensed to ARCHEMIX ($17.5M)
liposomal drug delivery technology:
Side effects and administration problems of potent compounds can be solved
New patent obtained by new formulation
AmBisome®
Phospholipid
bilayer
Lower toxicity of amphotericin B
Affinity for ergosterol in fungal cell
membrane
Amphoterician B
molecules
Triangle Pharmaceuticals
Acquisition in Jan,2003 for $464 million
Keep founds
flowing to R&D in
ATV created field
• Triangle researches were
focused on therapies for
HIV and HBV
Similar and
complementary
profile to Viread
• Co formulation
emtricitabine/Viread into
one pill
U.S. approval, 2004 of TRUVADA®
Corus Pharma
Acquisition in Aug, 2006 for $365 MILLION
Moving into new
therapeutic areas
• establishing a center of
expertise in respiratory
therapeutics for the company.
Unmet medical
needs
• Phase III aztreonam lysine for
inhalation for cystic fibrosis
treatment
CF impacts the lives of more than 70000 people
Aztreonam lysine was granted orphan drug status
Raylo Chemicals Inc
Nov, 2006 for 107 million Euros
improve existing
commercial
manufacturing
processes.
• manufacturing of API for
investigational and commercial
products
Myogen
nov.17,2006 $2,5 Billion
Inhances growing focus • Research program in non-infection lung
on cardiopulmonary dvpt disorders
Marketed or early stage
drugs
Unmet medical need
• Darusentan,Ambrisentan in clinical
dvpt
• Flolan marketed since 1995
• PAH, resistant hypertension
11 Products Contributing to Revenue Stream
Through Direct Sales or Partner Promotion
HIV / HBV
Foster City / Durham
$25 billion in 2011
In 2007 The antiviral market was
valued near $18 billion
22
Antiviral
Emtriva®
Viread®
Emtricitabine
(tenofovir disoproxil fumarate)
A once-daily oral (NRTI). in
combination
A once-daily oral (NRTI) in
combination with other ART.
U.S. and E.U. approval, 2003.
U.S. approval, 2001; E.U. 2002
Truvada®
A fixed-dose once-daily
U.S. approval, 2004; E.U.
approval, 2005
BMS
Sustiva®
(efavirenz)
NNRTI
Atripla®
The first and only once-daily single tablet
regimen for the treatment of HIV infection
in adults.
U.S. approval, 2006 / EU dec,2007
Hepsera® :(adefovir dipivoxil)
First, to treat HIV but…
A once-daily oral NRTI for the treatment of
patients with chronic hepatitis B.
U.S. approval, 2002.
E.U. approval, 2003.
Vistide® : (cidofovir injection)
An antiviral injection, treatment of
CMV
retinitis in adult patients with AIDS.
U.S. approval, 1996; E.U. approval,
1997.
Seattle
Tamiflu®
(oseltamivir phosphate)
The first orally neuraminidase inhibitor
(influenza A and B)
FDA: treatment Oct1999 and for
prevention in Nov2000.
Available in Europe since 2002.
The product, which was developed by
Gilead, is commercialized globally by
Hoffmann-La Roche.
•Roche pays royalties
to Gilead based on a
percentage of the net
sales generate from
Tamiflu worldwide
Others
AmBisome® :
(amphotericin B liposome for injection)
A treatment for systemic fungal
infections in adults.
E.U. approval, 1990; U.S. approval,
1997.
Macugen® : (pegaptanib sodium injection)
An injection for the treatment of neovascular age-related macular
degeneration (also known as "wet" AMD)
This product is marketed in the United States by OSI Pharmaceuticals.
Royalties to Gilead
U.S. approval, 2004.
Cardiopulmonary
the new expectation
ARTERIAL PULMONARY HYPERTENTION
•It is estimated that about 200,000 suffer from PAH world wide.
•High blood pressure in the pulmonary artery (exceeding 25 mmHg)
•Increased circulating levels of ENDOTHELIN have been observed
in patients with PAH
vasodilatation
Vasoconstriction
Cell proliferation
ETA
ETB
A high level of ENDOTHELIN will have as consequence:
Pulmonary
vasoconstriction
Hypertrophy
Fibrosis
Right ventricular
strain and
disfunction
ENDOTELIN has emerged as a key mediator in the pathophysiology and its
antagonism is established as a therapeutic strategy in PAH.
FIRST IN CLASS :
Tracleer®(Actelion Inc) a non selective antagonist orally active drug.
In 2007 Tracleer sales were $1,18 billion.
GILEAD’ S PRODUCT
LETAIRIS(Ambrisentan) was approved as a selective ETA receptor antagonist
orally active drug in 2007.
Parity pricing to Tracleer has helped with reimbursement.
Main patients sources :
•Naïve patients.
•Tracleer patients with elevated LFTs(liver toxicity)
•SILDENAFIL monotherapy poor responders
Commercialized by GSK outside of US ($1 billion expected in 2010)
Flolan®
(Epoprostenol sodium for injection)
An analogue of prostacyclin PGI2
Effects vasodilation which in turn lowers the blood pressure
A long-term intravenous treatment for primary pulmonary hypertension.
U.S. approval, 1995.
Total revenues
+47%
$3,135
3500
$ in millions
3000
$2,127
2500
2000
Regular increase 2006/2007
Mainly due to HIV franchise
48%
2005
$1,419
2006
1500
2007
1000
500
0
YTD
Significative part of royalties in
total revenues
Product sales
2,3B
Product sales ($ Billions)
2,5
2
1,5B
1,5
2006
2007
1
0,19B
0,23B
0,5
0,16B
YTD
0,16B
0
Hepsera
AmBisome
others
HIV franchise
Atripla approved in 2006 and brought near $904 Million in 2007 just in USA
Truvada 1,59B in 2007
Current U.S. Share of Treatment
• Gilead is Capturing ~
81% of HIV-infected
Patients New to
Therapy
• European AIDS Clinical
Society recommend
Truvada as one of the NRTI
backbones of choice
Based on Synovate Healthcare HIV Monitor of all patients initiating
therapy in Q3 2007
Favorable Profile of Gilead’s HIV Products
N
R
T
I
Based on Source® Weekly PHAST, 8/6/04 – 12/21//07, Wolters Kluwer Health
Royalties
Tamiflu® sales by Roche key contributor to royalty
Increase in demand for Tamiflu
purchase of $2 billion
of Tamiflu by US
government !
Tamiflu is the primary recommanded antiviral of choice for patients infected
with H5N1
15 external contractors for
manufacture
increase demand and low stock pilling
In 2007
Tamflu royalities were $414,5M (13% )
Production capacity for
Tamiflu
R&D EXPENSES
410
380
2007
 Increased headcount
Increased clinical study expenses related to
cardiopulmonary program and lung infections
$5 million up-front license fee to Parion Sciences, Inc.
Product pipeline
PHASE I
PHASE II
PHASE III
File new drug
application
GS9131
HIV/AIDS
Elvitegravir
Darusentan
Viread
GS9190/HCV
polymerase inh
Integrase inhibitor
Resistant
hypertension
HBV
Aztreonam lysine
Cystic fibrosis
(P. aeruginosa)
GS9191
HPV
GS9310/11
Fosfomycin/tobramycin
CF
GS9219
Hematologic
cancer
antivirals
respiratory
cardiopulmonary
oncology
 HIV prevalance
Run clinical trail
GILD Access Program
Generics companies
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Worldwide, at least 80% of those in need of treatment
for HIV/AIDS lack access to anti retroviral medications
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(ARVs) .
RUN CLINICAL TRAIL
NIH; FHI had launched an intervention to use of the oral antiretroviral drug
Viread as a (PREP) in high-risk groups ( uninfected women who have highrisk commercial sex …)
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Protests against Trials of PREP
In 2004 dramatic protest against the Cambodian trial at the XV
International AIDS Conference in Bangkok, caught the world’s
media attention
Reasons cited by the activists :
• Inadequate prevention counseling by investigators,
• Lack of pre- and post-test HIV counseling,
• Nonprovision of medical services.
• Safety of tenofovir for longterm use by individuals who are HIV
negative has not been established .
• participants take all risks and get little of the benefits.
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consequences
• In July 2004, pressure from activist groups and affiliated nongovernmental organizations persuaded the Cambodian Prime
Minister to halt the initiation of a PREP trial of tenofovir among
Cambodian commercial sex workers
• In February 2005, a similar trial in Cameroon, was halted by the
Minister of Public Health
• March 11, 2005, FHI Nigerian arm of the tenofovir PREP trial
discontinued prematurely.
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GILD Access Program
In 2002, provide the drugs throughout the world at reduced prices based
on a country’s economic status and HIV prevalence.
35
47
Even though about 1 million patients were on GILD’s HIV
treatments worldwide,this was well short of the company’s goal of
10 million, the majority of whom would be in poor countries.
No familiarity with healthcare’s systems
This program had succeded ???
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Gilead & Generics companies
In 2005 Aspen Pharmacare Holdings Ltd. non-exclusive rights to
manufacture Viread and Truvada for all of the 98 poorest countries and to
distribute the drugs in every country in Africa.
In 2005, GILD partnered with PharmaChem Technologies Ltd. to open a
manufacturing facility for Viread in the Bahamas ease access in lowincome countries in the Caribbean and Latin America
In 2007 Gilead provide voluntary, non-exclusive licenses to 10 Indian
generic pharmaceutical companies for the manufacture of viread and
truvada
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Why Generics companies?
Generic erosion
generic drug companies are aggressively attacking patented drugs
Familiarity with their healthcare systems
Give a second product lifecycles for viread , emtriva and truvada
New markets and infrastrucutre
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Strengths
Weaknesses
Leading position in the virology market
Lack of manufacturing capability
Ability to use liposomal technology to
revive aged anti-infective products
Dependence on small number
of distributors in the US
Opportunities
Threats
New acquisitions
Regulatory changes
GILEAD and BMS (COMBO)
Illegal export
Epidemic of bird flu
New resistances in HIV
Growth of HIV, HBV and HCV therapy
markets
Significant competition
Generic erosion
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conclusion
Gilead is a biopharmaceutical company which is growing
through its strategic acquisitions and partnership
slowly but certainly ...
Paul Berg, PhD
Nobel Prize Winner
John C. Martin, PhD
President and Chief Executive
Officer
James M. Denny
Chairman
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references
•
•
•
•
PLoS Medicine |
www.plosmedicine.org
Company-History.html
•
http://seekingalpha.com/symbol/gild
•
26th Annual JPMorgan Healthcare
Conference
January 7, 2008
•
Q3 2007 Earnings results Oct,18 ,2007
BioCentury ;Unleashing market forces
Gilead Sciences, Inc. Company Profile
Reference Code: 2499Publication Date:
Jan 2007
Archemix http://www.archemix.com
(accessed December 2002)
•
•
EUROPEAN RESPIRATORY REVIEW,
2007;16: 13-18.
doi:10.1183/09059180.00010204
•
http://www.fundinguniverse.com/co
mpany-histories/Gilead-Sciences-Inc-
www.gilead.com