Rigel Pharmaceuticals Inc has initiated clinical testing in the United States for the company's first product, a drug to treat allergic rhinitis.

The experimental compound, R112, is the first of a new class of drug directed at immune blood cells called mast cells. Activation of these cells is one of the earliest steps in the initiation of an inflammatory response in allergy and asthma.

"Rigel's investigational drug represents a novel approach for intervening in the allergic process," said Harold S. Nelson, the study's lead investigator and professor of medicine at National Jewish Medical and Research Center in Denver, one of the leading asthma and allergy centers in the United States. "Because it has the potential to block all components of the mast cell response, and because it can be easily administered by nasal spray, R112 could offer a new strategy for treating allergic rhinitis as well as perhaps other allergic diseases of the respiratory system."

When an allergen enters the body, a protein called immunoglobulin E (IgE) binds to mast cells, in essence turning them on and telling them to initiate an allergic reaction. Mast cells then release a host of chemical mediators, including histamine and leukotrienes, that create common allergy symptoms. When this process occurs repeatedly over time, it creates persistent inflammation of the nasal passages, resulting in chronic congestion. R112 targets mast cells after they have been turned on by IgE and prevents the release of mediators.

However, unlike common allergy drugs such as antihistamines or antileukotrienes that block only a single mediator, R112 is designed to block all of the major pathways that are triggered following mast cell activation.

Because of this broad effect, Rigel anticipates that R112 could be used to treat the more chronic component of allergic rhinitis.

Rigel began clinical testing of R112 last September in Britain. In that initial safety study, conducted with normal volunteers, no significant adverse events were observed. The trial now underway at National Jewish Medical Center will evaluate the effectiveness of R112 in 20 patients with documented allergies. It is a randomized, double-blind, placebo-controlled "crossover" trial. In this design, patients serve as their own controls, in effect doubling the size of the study sample. Preliminary findings from the trial are expected towards the middle of the year.

The market for drugs aimed at chronic allergic rhinitis is potentially very large. Currently, this condition is most often treated with inhaled steroids such as Flonase. Sales of these products exceed $2 billion annually in the United States alone. In addition, a number of the most popular inhaled steroids are due to lose patent protection in the next few years, creating an opportunity for new products to enter the marketplace. Therefore Rigel believes that, if shown to be safe and effective, R112 could readily become an alternative to chronic steroid use among allergy sufferers.

Rigel already has advanced research and development programs underway in both asthma and autoimmunity. The company expects to begin clinical testing of a mast-cell drug for one of these indications later in the year.