Clinical trials clearly illustrate the effectiveness of NeutroSpec in confirming appendicitis in suspected cases. Hypersensitivity
reactions represent a serious potential product side effect. Side effects noted during trials included hypotension, worsening
of sepsis, flushing, and dyspena.
Macugen (pegaptanib sodium injection) is a synthetic pegylated oligonucleotide aptamer that specifically binds vascular endothelial
growth factor (VEGF). It is indicated for the treatment of age-related neovascular ("wet") macular degeneration, which results
from the proliferation of abnormal blood vessels in the eye, leading to retinal damage and vision loss. The process of vascularization
(angiogenesis) is fueled by VEGF. Macugen adopts a three-dimensional shape that allows it to interact specifically with VEGF,
thereby inhibiting its activity (note that the monoclonal antibody-based product Avastin achieves a similar effect in the
context of cancer).
FDA approved it in December, 2004. It is manufactured by Gilead Sciences for Eyetech Pharmaceuticals and Pfizer.
The RNA-based oligonucleotide consists of 28 nucleotides of pre-defined sequence, chemically modified to render the product
resistant to nuclease degradation. Two 20-kDa polyethylene glycol (PEG) molecules are covalently attached at one end of the
nucleotide (to increase in vivo half life), yielding an overall product molecular mass of some 50 kDa. Final product is presented as a sterile, WFI-based
solution containing sodium chloride as well as sodium phosphate as excipients. The product is administered by direct intravitreous
Clinical assessment centered upon two studies involving almost 1,200 wet AMD patients. While both control and product groups
continued to experience vision loss, the rate of vision decline experienced by Macugen-treated patients was significantly
slower than in the case of control patients. The most frequent potentially serious side effects noted included endophthalmitis,
retinal detachment, eye inflammation, irritation, and blurred vision.
Tysabri (natalizumab) is a recombinant, humanized IgG-based monoclonal antibody produced in engineered murine myeloma cells. It is
indicated for the treatment of patients with relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations.
Subsequent to its biosynthesis and purification, Tysabri is formulated as a concentrate (20 mg/mL), indicated for once monthly
Tysabri binds specifically to selected integrins found on the surface of most white blood cells (with the exception of neutrophils).
These integrins serve as recognition docking markers, allowing binding to vascular endothelial cells and thereby facilitating
leukocyte migration across the endothelium. Tysabri administration blocks this interaction and increases the numbers of circulating
leukocytes in the blood by inhibiting transmigration out of the vascular space.
While the exact underlining causes of multiple sclerosis remain to be elucidated, the condition is believed to be an autoimmune
one in which selected immune system cells (leukocytes) attack the central nervous system. Tysabri therefore may work by blocking
migration of such leukocytes across the blood-brain barrier (comprised of endothelial cells lining brain capillaries), and
hence preventing them from damaging the neuronal tissue.
The product is manufactured by Biogen Inc. and distributed by Elan. Initially approved by FDA in November, 2004, marketing
and its use in ongoing clinical trials were halted in February 2005. The product received accelerated approval as it appeared
to provide a substantial benefit to MS sufferers. One clinical trial recorded a reduction in the frequency of relapses by
two-thirds (relative to placebo). A second trial (in which patients also received the interferon-based product Avonex, but
for which Avonex did not prevent relapses) was also undertaken. Tysabri reduced the frequency of relapse by 50 percent in
FDA evaluation was based upon results from trials ongoing for one year. At that stage the most serious adverse events noted
were infections and temporary hypersensitivity reactions. Approval was contingent upon continuing the trials for a second
year. This data initially revealed one fatal and one additional case of multifocal leukoencephalopathy (PML). Both patients
had received Tysabri in conjunction with Avonex for two years. The product remains withdrawn for all clinical use until ongoing
investigations are completed.
Gary Walsh, Ph.D., is senior lecturer in the Industrial Biochemistry Program of University of Limerick, Limerick City, Ireland, 3126.96.36.1994,
fax 3188.8.131.528, Gary.firstname.lastname@example.org
1 Walsh G. Biopharmaceutical benchmarks 2003. Nature biotechnol. 2003; 21:865-870.
2 Biotechnology Industry Organization. Milestones 2004 Report. Available at
3 Pavlou AK, Reichert JM. Recombinant protein therapeutics - success rates, market trends and values to 2010. Nature biotechnol. 2004; 22:1513-1519.
4 Reichert JM, Pavlou A, Monoclonal antibodies market. Nat. Rev. Drug Discovery 2004; 3: 383-384.