Protein delivery options: how well have we succeeded?

Of the ten top-selling drugs in 2013, the first three (Humira, Enbrel, Remicade) were all monoclonal antibodies for treating autoimmune diseases; together these three accounted for approximately $28 billion in sales. Another antibody, Avastin, indicated for bowel cancer, accounted for $6.7 billion among these top-selling drugs, while Herceptin, used to treat breast cancer, had sales of $6.6 billion. These numbers bear eloquent testimony to the increasing demand for protein therapeutics. All of these proteins are made by recombinant synthesis which has truly revolutionized the ready availability of human analogs. Such antibodies are administered via subcutaneous injection or via intravenous infusion; the frequency of administration varies. For example, Enbrel is injected subcutaneously once a week for rheumatoid arthritis whereas Remicade dosing is 3 mg/kg given via intravenous induction at 0, 2 and 6 weeks. While the number of protein therapeutics has grown substantially over the last decade [1], delivery systems continue to be limited. We examine the reasons for this and discuss what we can expect in the future. Innovations in delivery system are driven by the following factors: