Product case study Macugen

Macugen (tradename) is the first and thus far only aptamer approved for general medical use. It was approved by the FDA in December 2004. The product is a synthetic PEGylated oligonucleotide with binding specificity for vascular endothelial growth factor (VEGF). It is indicated for the treatment of neovascular ('wet') age-related macular degeneration (AMD).

The RNA-based aptamer consists of 28 nucleontides of predefined sequence, chemically modified in order to render it resistant to nuclease degradation. Two 20 kDa PEG molecules are also covalently attached at one end of the nucleotide. The overall product molecular mass is 50 kDa. Final product is presented as a sterile solution containing sodium chloride and sodium phosphate as excipients.

The target indication (age-related neovascular or 'wet' macular degeneration) results from the proliferation of abnormal blood vessels in the eye, which leads to retinal damage and loss of vision. The process of vascularization (angiogenesis) is driven by VEGF. Macugen adopts a three-dimensional shape that allows it to interact specifically with VEGF, thereby inhibiting its activity (the monoclonal antibody-based product Avastin, Chapter 13, achieves a similar effect, but in the context of cancer). The product is administered directly to the site of action by intravitreous injection. Absorption from the eye into the general bloodstream occurs only very slowly, allowing a frequency of administration of once every 6 weeks. Subsequent product metabolism is via nuclease degradation.

Initial clinical assessment involved some 1200 wet AMD patients. Although 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 during these trials were endophthalmitis, retinal detachment, eye inflammation/irritation and blurred vision, although rare cases of anaphylaxis have also been reported. Macugen is marketed by Eyetech Pharmaceuticals and Pfizer.

Transplantation entails the transfer of living cells/tissue/organs from a donor to a recipient. In some cases (e.g. many skin grafting procedures) the donor and recipient are actually the same individual, and this is termed autologous transplantation. More usually, however, the donor and recipient are different individuals, and this is termed allogeneic transplantation.

Common forms of transplantation include whole blood transfusions (Box 14.5), bone marrow transplantations, skin grafting and transplantation of a wide range of organs, including kidneys, liver, pancreas, lungs and heart. Improvements in surgical transplant techniques, along with the availability of effective immunosuppressive drugs (including some antibody-based drugs; Chapter 13), render 1-year success rates for most organ transplants in the 75-95 per cent range.

Tissue/organs destined for transplant are rarely considered to be pharmaceutical products. The material for transplant is usually harvested directly by clinicians via surgical or other appropriate techniques, followed by direct transplantation without significant in vitro processing.

'Tissue- or cell-engineered' products represent a small but significant subgroup of cell-based products. Such products also consist of/contain fully differentiated cells but do undergo some

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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