azci presents: antivenom fda approval

21

Upload: anitabell

Post on 07-Jan-2017

138 views

Category:

Small Business & Entrepreneurship


0 download

TRANSCRIPT

ARIZONA CENTER

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.

Antivenom is Antibodies

• Serotherapy (1st

generation)

• Immunotherapy (2nd)

• “Fabotherapy” (3rd)

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