Drugs Xagena
Current standard immunomodulatory therapy with interferons ( IFNs ) for relapsing-remitting multiple sclerosis exhibits proven, but limited, efficacy and increased side effects due to the need of frequent application of the drug. Therefore, there is a need for more effective and tolerable drugs.
Due to their small size, optimization of therapy with interferons in multiple sclerosis by PEGylation is feasible. PEGylation of an Interferon means that at least one molecule of polyethylene glycol ( PEG ) is covalently added. This modification is a standard procedure to increase the stability, solubility, half-life, and efficacy of a drug, and is applied in several drugs and diseases.
Currently, a therapy regimen applying PEG-Interferon beta-1a in multiple sclerosis is being developed to achieve an optimized relationship between therapy-related side effects and pharmacokinetic / pharmacodynamic efficacy.
Phase I studies have demonstrated that subcutaneous PEG-Interferon beta-1a at a dose of 125 mcg every 2 or 4 weeks might be at least as efficient and safe as the current standard therapy with Interferon beta-1a.
A global Phase III clinical study is investigating the efficacy of PEG-Interferon beta-1a ( Plegridy ) in terms of reduction of the relapse rate in relapsing-remitting multiple sclerosis patients.
The latest primary safety and efficacy analysis after 1 year has revealed a favorable risk-benefit profile with no significant difference between dosing regimens.
Compared to placebo, the annualized relapse rate was reduced by about one-third and new or newly enlarging T2 brain lesions were reduced by about one-third when dosing every 4 weeks or by two-thirds when dosing every 2 weeks. This presents a significant effect of the dosing interval, favoring administration every 2 weeks.
Chronic administration of PEGylated proteins mostly at toxic concentrations causes vacuolation of renal epithelium in animals, which, along with the issue of occurrence of anti-PEG antibodies, has to be addressed by phase IV studies. ( Xagena )
Reuss R, Biologics 2013;7:131-138
XagenaMedicine_2013
