Presentation reviews legal, regulatory and marketplace challenges to implementing an abbreviated pathway for "generic biologics" in the United States.

1. “Generic”Perspectives on the
Future of BioSimilars
BIOCOM
Life Sciences Venture Network
San Diego, California
February 6, 2008
Michael A. Swit, Esq.
Vice President, Life Sciences

2. Standard Disclaimers
•Views expressed here are solely mine and do not
reflect those of my firm or any of its clients.
•This presentation supports an oral briefing and
should not be relied upon solely on its own.
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3. Small vs. Large Molecule Realities
• Small Molecule • BioSimilar
– Therapeutically equivalent – Not therapeutically equiv.
• Same molecule • Not same molecule
– Substitutable – Not substitutable
– Price drives–and multiple – Price difference to brand likely
generics drive price down smaller
– Insurance coverage follows – Separate coverage likely for the
ANDA approval BioSimilar
– Marketing –cost sells; little – Will require professional sales and
need for formal sales & marketing staffs to drive
marketing staff utilization vs. “Brand”
– Legal Pathway –clear under – Legal Pathway –
Waxman-Hatch Act • 505(b)(2) –case-by-case
• PHSA -- nonexistent
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4. Therapeutic Equivalence
• Lynchpin to generic process –depends on:
– 1. Pharmaceutical “ equivalents”–active ingredient, dosage
form, strength, etc., must be SAME.
• highly unlikely with BioSimilars –
– Characterization -- still a challenge even for the innovators –clinical
trials may be needed to show comparability after process changes
– Chances of “ equivalence”conclusions faint as even a single amino acid
can throw off conclusion (e.g., HGH)
– Lovenox –only 70% characterized (but, is under an NDA) –no FOP
• Janet Woodcock, FDA Deputy Commissioner & CMO (before
Congress, March 2007):
–“ there is general recognition that the idea of sameness, as the term is used in
the generic drug approval process under the Federal Food, Drug, and
Cosmetic (FD&C) Act and applied to small molecules, will not usually be
appropriate for more structurally complex molecules of the type generally
licensed as biological products under the Public Health Service Act.”
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5. Therapeutic Equivalence
•Lynchpin to generic process –depends on:
–2. Bioequivalence study (occasionally clinical studies
with efficacy endpoints –e.g., topicals) –
•Accurate predictability also allegedly an issue with
BioSimilars
•Biosimilars –even under an abbreviated pathway, will most
likely more resemble an NDA than an ANDA –clinical
studies to show efficacy and monitor immunogenicity
concerns
– Omnitrope® -- Sandoz’ HGH product –rumored to have cost
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tens of millions of dollars to develop
•This is not your father’ generic model!!
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6. How Omnitrope® Approved
• Under 505(b)(2):
– Physicochemical testing found highly similar structure to
Genotropin
– New non-clinical pharmacology and tox data on OMNI itself
– PK, PD and comparative bioavailability data
– Clinical efficacy and safety data from comparative controlled
trials and long-term studies with OMNI
– Extensive clinical experience and literature on clinical effects
of HGH
– Not substitutable –no TE rating
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7. Substitutability
• Substitution -- core of classic Generic Industry Business Model
– Depends on therapeutic equivalence
– Allows for “ abbreviated”sales forces
– Price drives
• Multiple generics common –drives price to commodity status
• Biosimilar world –
– Substitution -- may evolve, but on a very, very limited basis
• Woodcock –must be able to handle repeated brand/follow-in switching
without adverse events
• HHS –June 2007 letter to Senate HELP Cmte –no interchangeability
• Thus, business model will not be multiple generics & not a commodity
– Without it, the Generic’ BioSimilar is really a branded drug
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• Must be marketed
• Will price be enough to drive utilizationf?
• Resistance from (a) physicians (b) patients?
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8. Price “Delta”–What Will It Be?
•Traditional Generic –
–First generic -- ± 70% of brand
drive price down to commodity
–Later generics –
•BioSimilar
–First “generic”–predicted to be more 10 –30% --
Omnitrope® -- launched at 20% off brand in EU
–Later generics – fewer w/Biosimilar; price drops less
–If price delta lower, “generic”utilization may be less
and slower
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9. Reimbursement
•Classic generic –is a lay-up; substitution drives
•BioSimilar
–Not clear; few examples
–Different products –not substitution based
–Formularies –state and private –will be a battlefield
for brand vs. “generic”reimbursement
•Efficacy and safety issues
–Will payers look for outcomes studies (which could
put pressure on both brand and generic)?
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10. Marketing Challenges
•Classic Generic –substitutability pushes sales
•BioSimilar
–“Generic”–will have to go out and detail
•Costs higher
•Not their sweet spot traditionally; although they learn fast
(remember, they are used to “ copying” )
•Will they run into greater resistance on “ substitution”
from doctors and patients
–Innovator –may need to distinguish vs. its “generic”
•Internal and external pressure for outcomes studies
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11. Legal Pathway
•Classic –Waxman-Hatch –Abbreviated NDA
and bioequivalence
•BioSimilar
–505(b)(2) –“ abbreviated,”but limited to those
proteins (e.g., HGH, Insulin, hyaluronidase,
glucagon, calcitonin, menotropins, ) that cleared
under 505(b)(1) and not Public Health Service Act
(PHSA)
–PHSA –no abbreviated pathway
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12. Active Ingredient Issues
• Classic Generic –many sources of API
• BioSimilar
– Technological barriers to API development greater; fewer
sources
– Foreign sources –particularly from China –will be under
great scrutiny from FDA
– Immunogenicity concerns are very high –
• FDA -- on record that immune response is “impossible to predict”
– see Dr. Janet Woodcock, FDA Deputy Commissioner, Congressional Testimony, March 26,
2007
• EU –one-year follow pre-licensing on chronic use products
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13. What’ Will 2008 Bring?
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• Rumor –Generics waiting for a Democratic President
• FDA FY 2009 Budget Proposal: FDA will seek new
statutory authority to allow FDA to approve “ abbreviated”
applications for certain biologic products licensed under the Public
Health Service Act (PHS Act). . . . The proposal will include: … .
a predictable and public guidance process for licensing FOPPs.
–
prescribe data required for FDA to review applications
–
require labeling for the safety concerns related to interchangeability
–
adequate intellectual property protections to preserve continued robust
–
research into new and innovative life-saving medications
– user fees
• Congress focus: Economy; War –will this happen this year?
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14. Post-Legislative Predictions
•Iterative process
–FDA will be very careful –we are in the post-Vioxx
world
–Innovators –will seek every possible battle ground to
slow BioSimilar approvals
•Petitions to FDA on approval criteria and other issues
•“Public process”for guidance
•Patents
– But, don’expect a Waxman-Hatch style process with 180-day
t
Exclusivity as a reward for challenging patents (although there is a
one-year for first “interchangeable”BioSimilar under 2007
legislation not enacted)
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15. Ancient Chinese Curse
May You Live In Interesting Times …
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16. Questions?
Call, e-mail, fax or write:
Michael A. Swit, Esq.
Vice President, Life Sciences
THE WEINBERG GROUP INC.
336 North Coast Hwy. 101
Suite C
Encinitas, CA 92024
Phone 760.633.3343
Fax 760.454.2979
Cell 760.815.4762
michael.swit@weinberggroup.com
www.weinberggroup.com
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17. About your speaker…
Michael A. Swit, Esq., is Vice President, Life Sciences at THE WEINBERG GROUP, where he develops and ensures
the execution of a broad array of regulatory and other services to drug and biologics clients seeking to market
products in the United States. His expertise includes FDA and CMS development strategies, compliance and
enforcement initiatives, recalls and crisis management, submissions and related traditional FDA regulatory activities,
labeling and advertising, and clinical research efforts.
Mr. Swit has been addressing critical FDA legal and regulatory issues since 1984. His multi-faceted experience
includes serving for three and a half years as corporate vice president, general counsel and secretary of Par
Pharmaceutical, a prominent, publicly-traded, generic drug company and, thus, he brings an industry and commercial
perspective to his work with FDA-regulated companies. Mr. Swit then served for over four years as CEO of
FDANews.com, a premier publisher of FDA regulatory newsletters and other specialty information products for the
FDA-regulated community. His private FDA regulatory law practice has included service as Special Counsel in the
FDA Law Practice Group in the San Diego office of Heller Ehrman White & McAuliffe and with the Food & Drug
Law practice at McKenna & Cuneo, both in the firm’ Washington office and later in San Diego. He first practiced
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FDA regulatory law with the D.C. office of Burditt & Radzius.
Mr. Swit has taught and written on a wide variety of subjects relating to FDA law, regulation and related commercial
activities, including, since 1989, co-directing a three-day intensive course on the generic drug approval process and
editing a guide to the generic drug approval process, Getting Your Generic Drug Approved. A former member of the
Food & Drug Law Journal Editorial Board, he also has been a prominent speaker at numerous conferences sponsored
by such organizations as RAPS, FDLI, and DIA. A magna cum laude graduate of Bowdoin College, he received his
law degree from Emory University Law School and is a member of the California, D.C. and Virginia bars.
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18. For twenty – five years, leading companies have
depended on THE WEINBERG GROUP when their
products are at risk. Our technical, scientific and
regulatory experts deliver the crucial results that get
products to market and keep them there.
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