Rigel Completes Clinical Trial of R112 in Allergic Rhinitis
R112 Demonstrates Inhibition of Allergic Chemical Mediators of Inflammation by Novel Mechanism
South San Francisco, CA
July 20, 2003
Rigel Pharmaceuticals, Inc. (Nasdaq: RIGLD) today announced the completion of its Phase I/II clinical study of R112, an experimental drug to treat allergic rhinitis, the chronic nasal congestion that afflicts approximately 20 to 25 percent of the U.S. population. The Phase I/II study evaluated the efficacy and safety of a single intranasal administration of R112 in volunteer patients with asymptomatic seasonal allergic rhinitis. Based on preliminary results, R112 in this study demonstrated significant improvement or consistent positive trends in reducing the release of chemical mediators involved in mast cell activation, one of the earliest steps in the initiation of an inflammatory response in allergy and asthma. Additionally, even though this particular study involved only a single dose of R112, improvements in symptom scores were noted, although not reaching statistical significance given the size of the study. No clinically significant adverse effects were attributed to R112 during this trial or in the prior Phase I clinical trial.
“We are extremely pleased with these preliminary study findings, which position inhibition of IgE signaling in mast cells with a small molecule drug as a promising approach for treating allergic rhinitis and possibly other respiratory-related allergic diseases such as asthma,” said Harold Nelson, MD, of National Jewish Medical and Research Center, the study’s Principal Investigator.
“Unlike current allergy drugs, such as antihistamines or antileukotrienes, that target only a single chemical mediator involved in mast cell activation, R112 may offer a new, comprehensive treatment strategy by potentially blocking all major chemical mediators of inflammation involved in mast cell responses.” said Donald Payan, MD, Rigel’s CSO and Executive Vice President.
“These preliminary results not only validate R112’s potential utility as a therapeutic for allergy,” said Elliott Grossbard, MD, Rigel’s Senior Vice President of Medical Development, “but provide important results to help us in the design of our multiple-dose studies in allergy patients.”
Study Design
Conducted at National Jewish Medical and Research Center, the study used the nasal allergen challenge model to test the efficacy of R112 in 20 volunteer patients with at least a two-year history of seasonal allergic rhinitis and confirmed reactivity to a specific allergen (grass or ragweed pollen extracts). The patients were randomized to receive either placebo or R112 in a nasal spray. The study was conducted in a double-blinded, cross-over manner for two allergen challenge exposures per patient at a two-week interval.
Future Plans
Based on the results of this study, Rigel intends to initiate multiple-dose safety and efficacy trials for R112 later in 2003. Additionally, upon completion of the statistical analysis of the results of the trial and as part of a scientific presentation of this study, Rigel intends to release further details of the results of the clinical trial later this year.
About IgE and the Allergic Cascade
Allergic rhinitis and asthma are chronic inflammatory disorders of the airways. Upon exposure to allergens, such as pollen, an allergic response is triggered resulting in inflammation and airway obstruction. In some patients, allergens such as pollen trigger the production of IgE antibodies that then circulate in the blood. IgE antibodies bind to mast cells and cross-link with their receptors, causing an intracellular signal that results in the release of various chemical mediators, including prostaglandins and tryptase. When this process occurs repeatedly over time, it creates persistent inflammation of the airway passages, resulting in the chronic congestion and airway obstruction associated with allergic rhinitis and asthma, respectively.
How R112 Works
R112 enters mast cells, binds to an intracellular target and interrupts the signal from the IgE receptor, thus preventing downstream signaling and subsequent chemical mediator release. 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. Currently, steroids are the major class of drugs that are able to block multiple mediators in the allergic response, but they have to be used selectively due to their global blocking of immune function. Because it is a small molecule compound, R112 can be delivered intra-nasally for allergic rhinitis and possibly in an inhaled form for the treatment of asthma.
About the Allergic Rhinitis Opportunity
The market for drugs aimed at allergic rhinitis is potentially very large, as allergic rhinitis is the most common allergic condition and is increasing in prevalence. Currently, this condition is treated most often with inhaled steroids and antihistamines. Sales of these products exceed $2 billion annually in the U.S. 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 become an alternative to the use of chronic steroid or single chemical mediator inhibitors (antihistamines or antleukotrienes) among allergy sufferers.
About Rigel (www.rigel.com)
Rigel’s mission is to become a source of novel, small-molecule drugs to meet large, unmet medical needs. Rigel has identified three lead product development programs: mast cell inhibition to treat immunologic diseases such as asthma/allergy and autoimmune disorders, antiviral agents to treat hepatitis C, and ligases, a new class of cancer drug targets. In addition to the clinical testing of R112, Rigel plans to begin clinical trials of two additional drug candidates, for the treatment of hepatitis C and rheumatoid arthritis, within the next twelve months. |
