Phase 3 Multicenter Comparative Study to Confirm Safety and Effectiveness of the F(ab)2 Antivenom Anavip.

Fewer than 200,000 crotaline envenomations occur annually in the US.Crotaline venoms contain
a broad variety of toxins, venom variability and injection quantity among individual snakes
and across species result in broadly variable patient presentations. Clinical consequences of
crotaline envenomation include local and systemic effects, both of which may progress for
hours to days.The best studied systemic consequence is coagulopathy, which may in its
complexity mimic disseminated intravascular coagulation. Platelet and clotting disorders
respond rapidly to administration of polyvalent antivenom.

Crotaline viper envenomation in the United States is treated with one of two licensed
products: Wyeth Antivenin (Crotalidae) Polyvalent (Polyvalent), or CroFab® (antivenin
Crotalidae polyvalent immune Fab, ovine). In recent years, both of these products have been
in critically short supply. Use of Wyeth Polyvalent has been associated with a greater than
75% incidence of adverse reactions, including acute type 1 and delayed type 2 immune
reactions.These phenomena are an inherent risk in the use of whole immunoglobulin. CroFab´s
low molecular weight creates a pharmacokinetic mismatch with crotaline venom which leds to a
recurrent venom effects.

Anavip is pharmacologically and pharmacokinetically different.Because of the elimination of
the Fc portion of the immunoglobulin molecule, Anavip is expected to produce far fewer
adverse reactions than seen with whole immunoglobulin antivenoms and unlike Fab molecules,
F(ab)2 molecules exceed the size threshold for renal clearance and thus are expected to
remain in circulation for a significantly longer time and substantially reduce the incidence
of recurrent coagulopathy.

Inclusion Criteria:

- Men and women 2 to 80 years of age

- Presenting for emergency treatment of pit viper bite

- Informed consent document read and signed by patient (or parent/legal guardian)

Exclusion Criteria:

- Current use of any antivenom, or use within the last month

- Current participation in a clinical drug study, or participation within the last month

- Positive urine or blood pregnancy test at screening

- Breast-feeding

- Allergy to horse serum, sheep serum, or papaya

- Underlying medical conditions that significantly alter platelet count or fibrinogen;
thrombocytopenia, hemophilia, familial dysfibrinogenemia, leukemia

- Use of any medication expected to affect platelet count, coagulation factors or
fibrinogen: chemotherapeutic agents, warfarin, heparin

- No clinical indications of snake bite requiring antivenom for treatment