azci presents: antivenom fda approval
TRANSCRIPT
Innovation Center
The Arizona Center for Innovation (AzCI) assists technology companies turning their innovative ideas into successful businesses through:
• Focused programs • World-class expertise • High-quality facilities
Access:• Other technology
entrepreneurs• Collaborative,
creative environment
• Advantage of hands-on support
• Successful business leaders
Arizona Center for Innovation
AzCI
Startup and emerging technology companies• Community and UA spin-outs
Technology• Aligned with UA Tech Parks and UA
International• Softlandings
Who
AzCI
Technology Areas: • Security and Defense• Mining• Agriculture and Water• Biotechnology• Intelligent Transportation and Vehicles• Renewable EnergyInformatics/Big Data/Advanced Manufacturing/Imaging/Optics/Photonics
Focus
Leslie Boyer, MDDirector, Venom Immunochemistry,
Pharmacology and Emergency Response (VIPER) Institute
Perspectives from AcademeAntivenom Development
Disclosure
• This speaker has every conflict of interest in the
book. I have been an investigator, an expert
witness, a consultant, a member of the
speaker’s bureau, and/or a gadfly for every
manufacturer and distributor of antivenom in the
US or Mexico excepting possibly Merck and
Birmex.
There is a global shortage of antivenom.
WHO, 2007: envenomation is a neglected worldwide disease: 5M cases, 200K deaths.
Why we care• Approximately 2,000,000 cases /year, worldwide
• Approximately 100,000 deaths
• Disability from amputation, contractures
• Worldwide, pharma has been getting out of the
antivenom business, leaving a huge medical and
economic gap
• Venoms are biologically fascinating, full of potential for
development of future pharmaceuticals and other
chemicals
Pre-1960
• MYN• Zapata• Inst de
Higiene
1960-1990
• Pharma• I de H ->
Birmex
1990-now
• Bioclon• Birmex…
Pre-1960
• Mulford• Merck• Myn• Wyeth ACP• ASC• Serpentaria
1960-1990
• Merck• Wyeth • ASU • Zoos• Bill Haast
1990-now
• Merck…• Wyeth…• Protherics• Bioclon• Zoos
Antivenom Availability in the U.S.
Antivenom Availability in Mexico
Antivenom Approvals, FDA
• 1927 Viper (Mulford)
• 1936 Black Widow (Merck)
• 1949 Scorpion (Myn)
• 1954 ACP (Wyeth)
• 1967 Coral (Wyeth)
• 2000 CroFab (Protherics)
• 2011 Anascorp (Bioclon)
The technological challenge
Old recipe, new rules: how to apply/ improve a
known concept to make safe, effective, but
low-cost antidotes
What “N” does it take?Product Eligible/yr Phase 2 and 3 trials Ratio
Merck Latrodectus 1000 ? ?
Wyeth Polyvalent 1000 ? ?
Wyeth M. fulvius 50 Efficacy panel N/A
Tab/Protherics CroFab
4000 42 1%
Bioclon Anascorp 150-15,000 15-2000 10% - 13%
Bioclon Analatro 2500 1oo??? 10%???
Bioclon Anavip 4000 >100??? 2.5%???
Coral???? 50-100 55??? 100???
Exotic (typical) <1 ? ?
Working with a small N and a potential market
Challenge of endpoint selection for statistics
Logistical challenge of multicenter design
Cost justifiable to Pharmabecause there is a good chance of later profit
“Normal” INDA with industry sponsor
Working with a small N and a public health problem
Antivenom recipients recovered faster, required less midazolam, and had lower
venom levels than placebo recipients.
NEJM, May 14 2009
• Ethical challenge of placebo design
• Funding challenge, requiring grants for rare condition
• Difficult for industry to justify• “Normal” INDA but with very
close academic collaboration
Working with a very small N• NOT worth the investment
for Pharma• Investigator-sponsored
INDA• Public Health involvement• Grant funded• Blood Products Committee
found clinical trials “neither ethical nor feasible”
• Historical Controls• Is a snake a “weapon”?• Future licensure very
uncertain
Working with an N of 1• Readiness for exotic snakebite is analogous to
military preparedness. We have millions of cobras, mambas and other snakes in US homes and collections.
• The most obvious answer is emergency depots kept for public use. But lacking a legal mechanism for this, we use zoos as our national system.
• “Zoo INDA” mechanism is related to Emergency Use IND.
• Essentially no physicians comply with the regulations.
If licensure is NOT feasible:http://www.fda.gov/cber/ind/antiven.htm#import
But who pays attention to quality
and safety here?
The future• US public policy: orphan drugs, exotic antivenoms, coral
snakes and zoos: we need a national antivenom policy
• FDA rules: public health exemption from PDUFA fees for
antivenoms should be explicit; animal rule should be
applicable under established guidance in cases where low
N make studies neither ethical nor feasible
• The world: we need legal, ethical and cost-effective ways
to collaborate internationally on neglected tropical
diseases that occasionally affect Americans.
https://techparks.arizona.edu/azci
©Arizona Center for Innovation 2015