Milestones and Moderate Progress in 2012 Drug Approvals - First gene therapy and plant-based expression vector products approved in 2012. - BioPharm International


Milestones and Moderate Progress in 2012 Drug Approvals
First gene therapy and plant-based expression vector products approved in 2012.

BioPharm International
Volume 26, Issue 4, pp. 54-56


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.

Voraxaze is a relatively large (83 kDa) homodimeric bacterial carboxypeptidase enzyme expressed in E. coli. It is approved for treatment of toxic plasma methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function. Methotrexate is an anti-folate antimetabolite widely used as a chemotherapeutic agent, but which itself exhibits a number of potential toxic side effects. It is excreted predominantly via the kidneys, with a typical half-life of 15 hours. Voraxaze, by hydrolyzing the carboxy-terminal glutamate residue from the methotrexate program, inactivates the latter, thereby alleviating potential toxicities in patients with impaired methotrexate clearance.

Jetrea and NovoThirteen are both produced in yeast-based systems. Jetrea contains a 27 kDa proteolytic enzyme and is used to treat vitreomacular adhesion. The condition is characterized by abnormal adherence of the vitreous gel within the eye to the retina, potentially leading to distortion or loss of vision. The adherence is mediated by vitreous proteins including laminin, fibronectin, and collagen, which are targeted by the product. NovoThirteen contains the A subunit of blood factor XIII and is used to treat congenital factor XIII A subunit deficiency.

Perjeta contains a humanized mAb that targets the extracellular dimerization domain of the human epidermal growth factor 2 protein (HER 2), found in association with a significant proportion of breast tumours. It binds to a different element of the HER-2 protein than does the previously approved Herceptin, and the product is used in combination with Herceptin (and docetaxel) in the treatment of HER-2 positive metastatic breast cancer.

The final product listed in Table I is Zaltrap, a recombinant fusion protein consisting of vascular endothelial growth factor (VEGF)-binding portions derived from VEGF receptors 1 and 2, fused to the Fc portion of a human IgG. The resultant 115 kDa dimeric glycoprotein acts as a soluble receptor for human VEGF, thereby preventing/reducing the biological activity of the latter. Zaltrap is approved for treatment of colorectal cancer, and the active ingredient is also marketed in a different formulation as Eylea, approved in 2011 for the treatment of age-related macular degeneration.

Gary Walsh, Industrial Biochemistry Program, Dept. of Chemical and Environmental Sciences and the Materials and Surface Science Institute, University of Limerick, Limerick City, Ireland,


1. G. Walsh, Biopharm Int., 25 (6), 34-36 (2012).

2. G. Walsh, Biopharm Int., 23 (10), 30-41 (2010).

3. G. Walsh, Biopharm Int., 22 (10), 68-77 (2009).

4. G. Walsh, BioPharm Int., 21 (10), 52-65 (2008).

5. S. Pearson, H.P., Jai, and K. Kandachi, Nat. Biotechnol. 22, (1), 3-4, (2004).

6. M.P. Ryan and G. Walsh, Trends in Biotechnol. 30, (12) 615-620, (2012).

7. EMA, Positive opinion on the marketing authorisation of Glybera (alipogene tiparvovec) (July 19, 2012).

blog comments powered by Disqus



GPhA Issues Statement on Generic Drug Costs
November 20, 2014
Amgen Opens Single-Use Manufacturing Plant in Singapore
November 20, 2014
Manufacturing Issues Crucial to Combating Ebola
November 20, 2014
FDA Requests Comments on Generic Drug Submission Criteria
November 20, 2014
USP Joins Chinese Pharmacopoeia Commission for Annual Science Meeting
November 20, 2014
Author Guidelines
Source: BioPharm International,
Click here