Vatalanib is an anti-angiogenic RTK (receptor tyrosine kinase) inhibitor. It disrupts intercellular communication through a well-known signaling pathway that has been implicated in the way cancer cells create new blood vessels from existing ones (angiogenesis). In particular, like Genentech's Avastin (bevacizumab), it blocks the vascular endothelial growth factor (VEGF) receptors, and so deprives certain tumors of the blood supply they need to grow. However, Avastin is taken intravenously, while PTK 787 is formulated as a pill. Phase III trials are ongoing. An NDA filing may be expected before the end of 2005.

Ruboxistaurin is a protein kinase C beta (PKC beta) inhibitor. Numerous studies to date have highlighted diabetic activation of PKC as a mechanism leading to the development of serious microvascular complications.

Ruboxistaurin promises to map entirely new medical terrain. A recent study on diabetic neuropathy from Decision Resources predicts that its launch will shift the market from pain control to disease modification.

In late November, Tysabri (natalizumab), the drug formerly known as Antegren, received approval for the prevention of multiple sclerosis (MS) relapses. That's also when it was renamed at FDA's request. An NDA had been filed on the basis of first-year results in two ongoing two-year Phase III trials in which Tysabri monotherapy reduced the rate of relapses by 66 percent compared with placebo—twice as effective as current drugs tested in other trials (which may void comparison).

A humanized monoclonal antibody with the potential to also treat rheumatoid arthritis (RA) and Crohn's disease, Tysabri is the first alpha₄-integrin antagonist in a new class of compounds known as selective adhesion molecule inhibitors, offering a new option to patients who have not responded to existing treatments. It appears to work by blocking alpha₄beta₁ integrin-mediated leukocyte migration across the blood-brain barrier and into inflamed tissue.

Tysabri requires only a monthly dose in contrast to existing MS drugs, such as the US market leader, Biogen's own Avonex (interferon beta-1a), which requires a weekly self-injection. But Tysabri must be infused intravenously. Its adoption, therefore, depends as much on logistics as on medicine. Biogen must not only persuade patients to go where they can undergo the one-hour procedure but also provide enough suitable locations. Estimates say there are only half the infusion sites needed.

Therapeutic Advance

Originally codeveloped by Celltech (now UCB Pharma) and Pharmacia (now Pfizer), CDP-870 reverted to UCB last year, when Pfizer terminated its rights after Celltech (as it was then called) declined to renegotiate terms.

A third-generation, antitumor-necrosis factor-alpha (TNF-a) antibody fragment (FAb), the drug represents a new approach to immunosuppression. The idea of the drug is to "shoot" the messenger, blocking the action of TNF-a, a cytokine that normally functions as a signal in the body's immune system to create inflammation. When overproduced, however, the result is often an inflammatory disease. Phase III studies show that CDP-870 significantly improves the quality of life for rheumatoid arthritis sufferers.