New formulation increases peptide stability

Aegis Therapeutics has unveiled a new formulation technology employing non-toxic excipients that maintain the physical stability and physiological activity of protein and peptide therapeutics while reducing immunogenicity.

ProTek technology permits the generation of easily manufacturable homogeneous and stable aqueous or lyophilised dosage forms of peptide and protein drugs and is applicable to all modes of administration including the injectable, intranasal, pulmonary, oral, oral cavity, and other transmucosal routes.

In accelerated stability studies using elevated temperatures and constant agitation for a period of three weeks, designed to stress the normal stability of a number of the most important and commonly used protein drugs, ProTek increased the stability of human growth hormone by more than five-fold and increased the stability of human insulin by approximately twenty-fold - in each case with no sign of decreased stability at the conclusion of the study.

Independent tests of ProTek with a novel peptide therapeutic currently slated for Phase II clinical trials have demonstrated similar results and in recent weeks have led to the first compound-specific license to be granted for ProTek, though the company did not reveal any details.

Protein therapeutics for which ProTek is expected to be particularly useful include insulin, human growth hormone, erythropoietin, interferon, Factor VIII, and a growing number of monoclonal antibody therapies.

"We believe that superior formulation stability for protein and peptide therapeutics will be a significant market differentiator as 10 per cent positive shift in market share could translate into a billion dollars or more over a product's normal life cycle," Don Grimm, chairman of Aegis Therapeutics, said.

"The prospect of a room-temperature stable insulin for use in insulin pumps could improve consistency and reduce the frequency with which the insulin cartridges must be replaced, or simply improve reliability and convenience of the current injectable insulins."

Protein aggregation, a particularly troublesome form of instability, may arise during the manufacturing process where peptides or proteins are often manipulated at high concentrations, or simply upon extended storage, and is increasingly being identified as a source of multiple deleterious effects for peptide and protein therapeutics.

These effects may include loss of efficacy, altered pharmacokinetics, reduced stability resulting in shortened product shelf-life or more stringent cold chain handling requirements, and unwanted immunogenicity.

Protein immunogenicity is receiving increasing scrutiny by the US food and Drug Administration (FDA) and other regulatory agencies as evidence mounts concerning potential adverse reactions to the resulting antibodies that arise in some patients.

Aegis said it licenses its technology on a product-by-product exclusive basis.