Dr. Swati Bal-Tembe - RIS

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Transcript Dr. Swati Bal-Tembe - RIS

Incentives for Innovation
Partnerships for Drug Development
Dr. Swati Bal-Tembe
May 12, 2011
International Conference on Equity and Access to Medicine
Role of Innovation and Institutions
Drug discovery and development
• New drug in the market > $1 billion
• Patents to protect market exclusivity
• Leverage for obtaining funds, technologies; or for
licensing/cross-licensing
• Attractive assets to potential investors, collaborators and
acquiring companies
• Strategy based on Company’s business model and business
environment
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Drug Discovery and Development
• HTS / Virtual Screening
• NP / Focused Library / Combichem/ Fast Follow-on
• Rational Drug design
Target
Identification &
Validation
Lead
Development
Preclinical
Studies
Clinical
Trials
IND
•
•
•
•
Market
NDA
NCE
Me-Too
Lifecycle Extensions
NDDS
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
“Me-Too Drugs”
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O
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Rosiglitazone
US 5,002,953
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O
S
N
O
N
O
N
H
Pioglitazone
US 4,687,777
O
F
F
H
O
F
N
O
Omeprazole
US 4,255,431
Dr. Swati Bal-Tembe
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O
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S
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O
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H
© 2011
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Lansoprazole
US 4,628,098
N
O
N
H
Pantoprazole
US 4,758,579
May 12, 2011
F
O
F
Markush Structure
We claim:
A compound of Formula 1
(RX)0-4
RA
L1
X
(RY)0-4
Y
L2
L3 RB
Formula 1
Wherein rings X and Y independently represent 5 to 7 membered
heterocycle, aryl or heteroaryl ring that may be substituted with 0-4
substituents described by RX and RY respectively
Wherein L1 is O, NH, CH2 or a bond
L2, L3
RA, RB,
RX, RY
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
CHALLENGES
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Challenges
• Crisis in the Pharmaceutical industry
• Patent cliff
• Expiration of blockbuster patents
• Fewer regulatory approvals of NMEs
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Measures
• Spending cuts, downsizing
• Focus
• Mergers, acquisitions
- Merck acquired Schering Plough for $41 billion in 2009
- Pfizer acquired Wyeth for $68 billion in 2010
- Sanofi Aventis to acquire Genzyme for $20.1 billion
• Line extensions, branded/authorized generics
• Collaborations – outsourcing, contract research
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Blockbuster Line-Extensions
To sustain revenue after Patent Expiry:
Crystalline forms (ranitidine), particle size (griseofulvin),
specific enantiomer, new uses, combinations
NDDS - novel formulations, extended release systems
• Nexium® (Esomeprazole) - single enantiomer
• Allegra® (Fexofenadine) - active metabolite (COOH)
minus the side effects of Seldane® (Terfenadine)
• Fosamax® and Prozac® – daily therapy to weekly
• Thalidomide ( Lenalidomide) – new use in multiple
myeloma
•
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
INVENTION AND INNOVATION
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Invention and innovation
• Strategy will have to focus more on inventions that have a
good chance of benefiting the patient
• The test of an innovation lies not (only) in its novelty, its
scientific content, or its cleverness but its success in the
marketplace
- Peter Drucker
• 3M
Dr Spencer Silver discovered the formula for an adhesive, but
Art Fry, a product development researcher, came up with a
marketable use for it in the form of Post-it® notes
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
OPPORTUNITIES
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
ABRAXANE®
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
To Market – Nanomedicines
• Paclitaxel, active ingredient in Taxol®, is poorly soluble in biological
fluids.
• Solubilizing agents often produce dose-limiting side effects
• Abraxis BioScience Inc. developed a nanoparticle formulation of the
potent anticancer drug paclitaxel
• Abraxane® approved in 2005
• Revenue >$ 300 million in 2007, 2008 and 2009
• Loading paclitaxel into a nanoparticle made of the natural protein
albumin eliminated the need for additional chemicals
• Targeted therapy
• Premedication with steroids or antihistamines that treat
hypersensitivity reactions caused by solvents not required
• Patients could be given higher doses of paclitaxel with fewer side
effects
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Elan v. Abraxis
• Elan Pharmaceuticals sued Abraxis BioScience, Inc. for patent
infringement
• Delaware district court jury awarded Elan $55.2 million in
damages for Abraxis's past infringement based upon a
reasonable royalty rate of 6%.
• Celgene acquired Abraxis for $2.9 billion in July 2010
• Elan has entered into a settlement and license agreement
with Celgene resolving the patent infringement litigation
involving ABRAXANE®
• Celgene will pay Elan a one-time fee of $78 million.
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
FIDAXOMICIN
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Fidaxomicin
Being developed by Optimer Pharmaceuticals, San Diego
Phase III trial results (Feb 2011): Superior to Vancomycin in the treatment of
Clostridum difficile infections. On April 7, 2011, FDA Panel unanimously
recommended approval of Fidaxomicin for the treatment of CDAD.
Patents issued for production method, polymorph, dosage forms, and method
of treatment of gastrointestinal infection caused by Clostridum difficile using
“R-Tiacumicin B”
Licensing deal with Astellas Pharma Inc. API manufacture - Biocon
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Fidaxomicin
• Antibiotics Tiacumulin A-F isolated by
fermentation of culture of
microorganism belonging to the
Actinoplanaceae family
• Patent application assigned to Abbott
Labs; filed in 1986, issued in 1990
• Activity against a number of Grampositive microorganisms; Clostridium
not specifically disclosed
• Except on sugars, stereochemistry not
specifically indicated
• “R-Tiacumicin B” is Optimer’s
Fidaxomicin
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
PLX4032
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Opportunities
• Difficult targets, new first-in-class drugs for unmet medical
needs
• FDA’s indicators of “innovativeness” – priority status
- Novel mechanism of action
- Novel structure
• Personalized medicine
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
PLX4032
• Presence of B-Raf gene mutation in over 50% of melanoma
patients and 10% in other cancers discovered in 2002 by Prof
Marais in the UK cancer research labs funded by the Wellcome
Trust
• Soon after discovery of the gene mutation, Plexxikon set up a
screening method for the discovery of inhibitors of the B-Raf
gene mutation using its scaffold-based drug discovery platform.
• Resulted in the discovery of PLX4032.
• Developed in partnership with Roche
• Companion diagnostic
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
PLX4032
• In 2006, Roche agreed to pay $40 million cash and up to
$700 million after reaching predefined milestones.
• Phase III trial (March 2011) showed that PLX4032 met coprimary endpoints of overall survival and progression-free
survival in patients with previously untreated metastatic
melanoma expressing the B-Raf mutation
• Daiichi Sankyo to buy Plexxikon acquiring rights to PLX4032
- Upfront payment of $805 million
- Near-term milestone payments of $130 million
- Daiichi Sankyo to gain certain co-promotion rights in the
USA for PLX4032, being jointly developed by Plexxikon and
Roche
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Opportunities
• Natural products – Bioprospecting
• Enabling technologies
• Less explored biodiversity, extreme conditions
- Convention on Biological Diversity (CBD)
- Convention on International Trade in Endangered Species
and Flora and Fauna (CITES)
• Biological deposits
• Patentability in different jurisdictions
• Biological material obtained from India
• Partnerships
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Microbial metabolites as pharmaceuticals
H
O
H3C
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CH2
NH2
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CH2
N
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O
H
O
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O
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S
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H
N
N
N
S
N
O
H
HO
S
S
N
CH2 H
N
N
N
O
O
N
N
H
O
O
NH2
CH3
O
H
PM181104
From marine microorganism Kocuria sp.
Partnership with NIO, Goa
Effective against resistant bacteria MRSA, VRE
PCT Publication: WO 2007/119201 (PLSL – CSIR)
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
PUBLIC-PRIVATE PARTNERSHIPS
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Public Private Partnership
Innovative partnership models
Antimalarial compound NITD609
developed through a Novartis led
collaboration: Novartis Institute for
Tropical diseases Singapore, Scripps
Research Institute, Swiss Tropical
Institute and the Public Health
Institute
Major support from the Wellcome
Trust, MMV, A*STAR Singapore and
the US Govt
© 2011
Dr. Swati Bal-Tembe
GlaxoSmithKline’s (GSK) drug
discovery center for diseases of the
developing world in Spain
Employs more than 100 scientists
Clinical development experts from UK
& US.
The GSK facility works closely with
the Medicines for Malaria Venture and
the TB Alliance
GSK is contributing a matching
number of staff and all remaining
overhead costs.
Around 1.5 million compounds have
now been tested for anti-TB activity
and four pre-clinical TB projects are
underway.
May 12, 2011
Public Private Partnership
Innovative partnership models
Eli Lilly and Company launched the “Lilly Not-for-Profit Partnership for TB
Early Phase Drug Discovery” research institute
International alliance with several public and private organizations
Partnership with groups such as Afya World Medicines Inc., the Infectious
Disease Research Institute, Jubilant Biosys and Academia Sinica, Taiwan
The company has opened its library of more than 500,000 Lilly medicinal
compounds to researchers
To conduct early-phase discovery research of new medicines to treat TB
including emerging resistant strains.
The AstraZeneca Bangalore Research Institute in India
Dedicated to finding a new therapy for TB that will act against drug-resistant
disease and reduce the duration of treatment.
In addition to the initial investment in buildings and state-of-the-art equipment
of US$20 million, AstraZeneca has committed a minimum of US$5 million a
year to supporting the research program.
More than 80 scientists recruited from leading research institutions and
universities now work at the facility
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
The Indian scenario
• DBT Mission Programme on "Screening for Bio-molecules from
microbial diversity collected from different ecological niches"
• First project in the country with industry & academia collaboration
to screen a large number of bacterial isolates isolated from diverse
ecological niches against targets for Cancer, Diabetes, Inflammation
and Infectious diseases
• Indian government initiative OSDD
Open Source Drug Discovery for compounds effective against latent
and drug-resistant TB
• Computation, Biology, Medicinal Chemistry, Preclinical, Clinical
• 2008-2012-2018
• No IP constraint
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Indian pharma companies at the crossroads
• Generic drugs
• Drug discovery research
• Money spent without guaranteed returns
• Different business models
- Go it alone
- Go it alone / licensing
- Licensing from Academia
- Research collaborations with universities/institutes
- Research collaborations with big pharma
- Contract research
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
INDIAN PATENT SCENARIO
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Indian patent scenario
• Provisions of Section 3(d)
– Higher standards for inventive step to discourage evergreening
• Efficacy data?
• Interpretation of “derivatives”
• New use exempted
• Evolving case law
• Strategy on opposing patents/patent applications
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
DUE DILIGENCE
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Due diligence
University/Small company/Large company model
Developing Strategy and Implementation
• Institutional IP Policy
• Ownership, title, assignment/licensing agreements
• Analysis of patents/patent applications/file histories
• Freedom-to-operate assessment
• Identify gaps in portfolio or potential blocking patents
• Strength of patents/patent applications
• Review and audit
• Costs
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Indian pharma companies at the crossroads
• Lifestyle diseases – eye on the global market
• Unmet medical need
• Neglected/Infectious diseases – Market? Recovering costs?
– “Orphan drug” type status – priority review?
– Tax benefits (Clinical trials)
– Validated herbal medicines
• Hybrid model
Public funding
Health Impact fund
Public-private partnerships
Guaranteed purchase contracts
Tax credits on sales
© 2011
Dr. Swati Bal-Tembe
Philanthropy
Corporate social responsibility
Drug donation
Differential pricing
May 12, 2011
Initiatives
Measures for reducing occurrence/recurrence of
infectious/neglected diseases
- Poverty alleviation
- Health, sanitation, nutrition, maternal and child health
- Safe water, minimize drug resistance
Development of rapid POC detection tests
Healthcare Management / Insurance
© 2011
Dr. Swati Bal-Tembe
May 12, 2011
Thank you
© 2011
Dr. Swati Bal-Tembe
May 12, 2011