Transcript www.massbio.org

The Potential and Possibilities for BioGenerics
Thursday, May 28, 2009
Bruce A. Leicher, Sr. VP and General Counsel
Momenta Pharmaceuticals, Inc.
Momenta Pharmaceuticals, Inc.
• Founded 2001 – Cambridge, MA – ~165 Employees
• Analytical platform developed at MIT in 1990s
• Initial Focus - Characterization Technology
 Complex Mixture Molecules: Heparins, Peptides, Biologics

Complex Generic Drugs

Follow on Biologic Drugs

Novel Biopharmaceutical Drugs

Molecular Diagnostics and Biomarkers
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Complex Biologic
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Structural Characterization
and control of the Manufacturing Process
• Characterization of:
 each species in the reference product
 its composition and sequence
• Batch-to-batch variability of the reference product
determined
• “Equivalence Windows” developed
 Captures inherent variability in manufacturing process
• Critical to ensure robust understanding of manufacturing
process for complex biopharmaceuticals
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Structure-Process: Leverage technology to
design and control manufacturing process
Characterization is critical to design and ensure robust understanding
and control of manufacturing process for complex biopharmaceuticals
Starting
Material
Step 1
Step 2
Step 3
Drug
Drug
Substance
Product
Integrated Momenta Characterization Analytics
 Product Starting Material
 Process Knowledge
 Process Parameters
 Product Quality
 Process Controls
 Quality-By-Design (QbD)
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Thorough Characterization Enhances Quality – But is
disruptive to the more standard FOBs development approach
(Illustrative)
Product
Knowledge
Standard Biosimilar
Momenta Follow-on-Biologic
Brand
Biosimlar
Brand
Biosimlar+
Brand
Biogeneric
Same
Same
Same
Same
Same
Same
Different
Different
Unknown
Unknown
Different
Different
Remove uncertainty.
Qualify differences.
Demonstrate equivalence.
•
Thorough characterization
•
Increased POS for approval
•
Manufacturing Process Design
•
Reduced (non)clinical requirements
•
Product Control and Quality
•
Better commercial differentiation
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Demonstrating Interchangeability Can Enhance
Quality
• Quality Improvements




Identifying structural variations associated with side effects
Enabling greater precision in identifying “contaminants”
Facilitating greater understanding of Manufacturing changes
Providing greater understanding of Product “drift”
• Advances in technology offer the potential for improved
manufacturing consistency
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FDA should balance the level of chemical characterization
with need for additional biological and clinical testing
1. Level of process and product
knowledge (characterization)
provided for the FOB will be key
when FDA sets the criteria for
Biogeneric and Biosimilar
approvals.
2. Biological and Clinical Testing, in
the absence of sufficient product
knowledge, will be inadequate to
qualify structural differences and/or
uncertainty between the FOB and
the Innovator – to justify
interchangeability.
Steven Kozlowski, PhD
Director, Office of Biotechnology Products,
OPS/CDER/FDA
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Interchangeability with the Innovator drug will be key
driver to commercial success in the U.S.
BIOSIMILAR
BIOSIMILAR+
Therapeutic Alternative
Therapeutic Substitution
Marketplace
FDA / Marketplace
FDA
Physician / Payor
Physician / Payor
Pharmacist / Payor
Omnitrope®  Genotropin®
TBD
Lovenox®  M-Enox
Contracting:
Retail / Hospital Chains
+++
+++
+++
Marketing / Sales
+++
++
+
N/A
TBD
+++
+
++
+++
How Determined
Decision Maker
Example
Direct Substitution
Market Share
BIOGENERIC
Interchangeable
Therapeutic Equivalence
Illustrative
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Competition that Allows Extended Brand Sales
Drug Price Erosion
(Illustrative)
1st Generic Launch
$1,200
Limited
Entrants
$1,000
1 Generic: ~15%
Price
$800
$600
3 Generics: ~50%
Retention
of
Brand
Earning
Potential
$400
7+ Generics: ~90%
$200
$-
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Markets with limited competition have potential
for significant economics
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Momenta Position – FOB Legislation
Clear Regulatory path to Interchangeability
No mandatory requirement for Clinical Trials
No mandatory requirement for public Guidance Documents
FDA to determine regulatory framework and criteria,
to be Driven by the Science
Appropriate period of Data Exclusivity for innovator
Certain and Fair Patent Process pre-Approval
– Ensure Incentives for Analytical Innovation –
– Ensure Highest Product Quality and Patient Safety –
-Encourages Innovative R&D Investment in Unmet Needs-
Competition, Investment and Innovation
Challenges
• Hatch Waxman was pro-competitive and pro-R&D
 Spurred innovation investment in novel, unmet needs rather than 3rd, 4th
and 5th entrants or life cycle management in a class of therapy
 Provided 5 years of exclusivity + patent term extension
 Permitted transparency for legal clearance of invalid or unenforceable
patents prior to launch of the generic
• Today, there is no legal pathway for generic entry of biologics
 Key incentive for Investment and Innovation
• BIO/PhRMA is seeking longer exclusivity as a condition of any new
legislation
 This would impede investment, and entry of competition
 This is not consistent with the greater number of patents covering the
making, using and selling of biologics
 Drugs have greater competition during their patent lives and less earning
potential due to the more limited scope of patent coverage
 This would reward “less innovative” R&D
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Patent Clearance Challenges
• Hatch-Waxman used the “Orange Book” to identify and facilitate
notice of patents that may be challenged as invalid, not infringed or
unenforceable
• To promote competition, the process must enable initiation of the
process early enough to allow for a generic launch when the patents
expire or are determined not to block a generic
• Biologics are challenging because of the complex array of patent
protection and multiple parties
 Early identification
 Early right to sue in advance of data exclusivity (following FDA
acceptance of filing)
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Questions?
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