Recombinant Oligoclonal Antibody Botulinum Antitoxins Are a Low-Cost Alternative to Equine Antitoxin

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Abstract
We have developed highly potent botulinum neurotoxin (BoNT) antitoxins consisting of three mAbs that bind non-overlapping epitopes and act synergistically to neutralize and rapidly clear circulating toxin. The resulting potency permits a low total antibody dose for treatment (34 mg for a seven-serotype product under the assumptions used here). Based on this high potency, the cost of producing the drug substance per dose is relatively low relative to chronic, high-dose antibody therapeutics. Recombinant human IgG also provides a longer serum half-life than equine F(ab’)2 antitoxin and therefore has potential for both treatment and prevention of botulism lasting for months. Here, we analyze the manufacturing costs of the recombinant antitoxin and the development costs of multivalent products and compare them to those of the currently approved equine-derived antitoxin. Approaches to reducing manufacturing complexity, including co-expression and co-purification, formulation, stockpiling, clinical use, analytical control, and multivalent antibody formats, are discussed. Our analysis indicates that recombinant oligoclonal BoNT antitoxins are not intrinsically cost-prohibitive and that development and overall manufacturing costs of Drug Product do not increase linearly with the number of serotypes covered.

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