SAN DIEGO, CA April 2, 2013/MarketWire – Concerns about the economic viability of biosimilars center around the high development cost relative to small molecule generics, and the difficulty of demonstrating bioequivalence for these complex molecules. In particular, immunogenicity of biosimilars is an area of increasing vigilance at both the FDA and EMA and poses a major risk for product failure and recall. Failure to demonstrate equivalent, or ideally lower, immunogenicity for a biosimilar is both costly and risky, since development of an unsatisfactory or inconsistent immunogenicity profile during development, or much worse, during post market surveillance, will be economically disastrous, mostly likely requiring costly reformulation and additional clinical studies.
Aegis Therapeutics’ patented ProTek® formulation technology provides for biosuperior formulations of biosimilars with no, or greatly reduced, immunogenicity and greater overall stability against aggregation and denaturation. Biosimilar formulations using Aegis’ ProTek® excipients as a replacements for polysorbate 80 or 20 (Tween® 80 or 20) avoid the oxidative damage caused by the peroxides, epoxy acids, and aldehydes that form spontaneously as the polysorbates oxidize in solution and provide for patent protected “biosuperior” innovator and biosimilar drugs.
Technical Background: Briefly, the most widely used non-ionic surfactants in protein formulations (i.e., to prevent aggregation) are polysorbate 80 and polysorbate 20 (Tween® 80 and Tween® 20 respectively). It is estimated that more than 70% of the marketed monoclonal antibody formulations contain one or the other of these two surfactants. Monoclonal antibodies in particular provide a stringent aggregation challenge because they usually require a relatively high dose (1 to 2 mg per kilogram) to allow for reasonable administration volumes by intravenous infusion or subcutaneous injection and of course the principal deleterious effects of aggregation for biotherapeutics are loss of efficacy and induction of unwanted immunogenicity.
Polysorbates (Tweens®) contain ether linkages (polyoxyethylene moieties) and unsaturated alkyl chains that spontaneously and rapidly auto-oxidize in aqueous solution to protein-damaging peroxides, epoxy acids, and reactive aldehydes including formaldehyde and acetaldehyde. These reactive species are produced continuously during and after manufacturing and during the time biotherapeutic products sit in inventory awaiting use so that the damage (and resulting immunogenicity) is a progressively worsening moving target. Since immunogenicity of biotherapeutics is an important focus of concern by the FDA1 and EMEA2 the need for nonoxidizing replacement surfactants is becoming acutely apparent. Aegis’ patented alkyl saccharide excipients provide such a non-autoxidizing nonreactive alternative to the polysorbates.
Replacement of polysorbates with a ProTek® excipient can eliminate the inevitable lot-to-lot variation in immunogenicity that occurs over time both in the developmental phase and post market assessment phase as a result lot-to-lot variation in levels of oxidative species in polysorbates. By eliminating the source of variable and progressively increasing immunogenicity (i.e. polysorbates) clinical trial lots and post approval lots will exhibit similar immunogenicity characteristics thus reducing the prospect of recalls if one or more later lots happen to show greater immunogenicity in post market analyses. Biosimilars in which the polysorbate is eliminated would be “biosuperior” from the standpoints of immunogenicity and patent protection through at least 2027.
To date, two Top-10 Big Pharma’s and a Top-5 multinational generics company are developing innovator or biosimilar biotherapeutics employing ProTek as a superior alternative to polysorbates.
For more information, please contact Aegis. General information about Aegis may be found at: www.aegisthera.com.
About Aegis Therapeutics
Aegis Therapeutics LLC is a drug delivery technology company commercializing its patented drug delivery and drug formulation technologies through product-specific licenses. Our Intravail® drug delivery technology enables the non-invasive delivery of a broad range of protein, peptide and non-peptide drugs that can currently only be administered by injection, via the oral, buccal, and intranasal administration routes, and with high bioavailability. Our ProTek® excipients stabilize, prevent aggregation, and reduce unwanted immunogenicity of protein and peptide therapeutics while avoiding the oxidative damage caused by polysorbate surfactants currently found in most protein injectable drugs.
1FDA Guidance for Industry, S8 Immunotoxicity Studies for Human Pharmaceuticals, International Conference on Harmonization (ICH) – Guidance for Industry: S8 Immunotoxicity Studies for Human Pharmaceuticals, http://www.fda.gov/RegulatoryInformation/Guidances/ucm129118.htm
2 ICH Harmonised Tripartite Guideline Immunotoxicity Studies For Human Pharmaceuticals S8, http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002851.pdf