PLANT-BASED EXPRESSION
The approval of Elelyso (taliglucerase alfa) by FDA in May 2012 represents another technological milestone, in that it is the first product approved for human use that is produced using a plant-based expression vector. Glycoprotein production in plant-based systems generally results in the formation of hyperglycosylated product containing various sugar moieties immunogenic in man. The sugar chains are devoid of sialic acid caps, which can negatively influence their serum half-life.
Elelyso is a recombinant human glucocerebrosidase used as a replacement therapy to treat Gaucher disease, a rare lysosomal storage disorder. The recombinant protein displays terminal mannose residues in its glycocomponent, facilitating direct product uptake by macrophages (the target cell type) via cell surface mannose receptors.
Interestingly, a parallel marketing authorization application for Elelyso submitted to the EMA was refused. However, the grounds for European refusal was not scientific in nature, but was due to the existence of a 10-year marketing exclusivity granted to a substantially similar product (trade name Vpriv), approved by the European Commission in August 2010.
ADDITIONAL APPROVALS
Among the additional products approved in 2012 is Raxibacumab injection, a human monoclonal antibody (mAb) approved by FDA for the prophylaxis and treatment of inhalational anthrax. The anthrax causative agent is the spore-forming Bacillus anthracis, and the infection can present as cutaneous, gastrointestinal, or inhalation formats, depending upon the route of infection. Inhalational anthrax is generally the most commonly fatal and would likely be the form of most concern in terms of bioterrorism. Raxibacumab specifically targets (neutralizes) the B. anthracis protein toxin.
The approval of three products produced in engineered E. coli cells (Gattex, Tbo-filgrastim, and Voraxaze) illustrates the continued utility of this prototypic expression system. Gattex (Revestive in Europe) is a short (33 amino acid) single-chain Glucagon Like Peptide 2 (GLP-2) analogue devoid of post-translational modifications. GLP-2 is known to promote increased intestinal blood flow, enhanced absorption of nutrients and maintenance of the small intestinal mucosa, hence the basis of product development as a treatment for short bowel syndrome caused by congenital defect, surgery, or disease associated loss of intestinal function.
Tbo filgrastim is another recombinant granulocyte colony stimulating factor used to treat neutropenia. The product is already marketed in Europe as Tevagrastim where it is classified as a biosimilar (to Amgen's recombinant G-CSF, Neupogen). However, it was assessed and approved in the US as an original biologics license application (BLA), because a biosimilar pathway was not available to the sponsor at the time of submission to the regulators.