Rigel Pharmaceuticals, Inc. has announced the presentation of clinical data for R112, the company’s lead candidate for the treatment of allergic rhinitis, during a poster session at the annual meeting of the American Academy of Allergy, Asthma and Immunology (AAAAI) in San Francisco, CA. The phase I/II single dose trial demonstrated that R112 was well tolerated and showed favorable biological effects.
The presentation entitled, “The Effect of a Novel Inhibitor of Mast Cell Activation on Mediators, Symptoms and Nasal Patency in Allergic Rhinitis,” reports data from the Phase I/II study, evaluating R112 for the treatment of allergic rhinitis. The study evaluated 20 patients in a randomized double blind crossover trial. One dose of R112 or vehicle control was given intranasally followed by nasal allergen challenge 15 minutes later. Chemical mediators and symptoms were then measured. Brenda Guyer, MD, will present the study results on Saturday, March 20, 2004.
The data demonstrated that subjects treated with R112 were indistinguishable from the vehicle controls across a wide range of clinical and laboratory safety tests. In addition to the positive safety data, the study demonstrated a statistically significant decrease in prostaglandin D2 (PGD2), a key immune mediator that was highly correlated with improvements in the allergic symptom of rhinorrhea. The study also showed other favorable responses.
“We are encouraged that the data demonstrates that R112 is well tolerated and has a positive safety profile,” said Donald Payan, MD, Rigel’s Chief Scientific Officer and Executive Vice President. “With these positive results and the promising decrease in PGD2, and other favorable changes, Rigel looks forward to further investigating R112 as a potential novel allergy therapeutic.”
Based on the success of this phase I/II trial, Rigel plans to initiate phase II efficacy trials in Q2, 2004. The randomized, placebo-controlled park study will provide broader indications of R112’s potential clinical value. The study will take place in two locations in different parts of the country, where patients will spend two days in an outdoor setting during the high-pollen season. Phase II results are expected in the second half of 2004.
About Allergic Rhinitis
Rhinitis is a common condition that affects nearly 40 million people in the United States—nearly 20 percent of the population. Rhinitis is characterized by inflammation of the nasal membranes accompanying symptoms that may include sneezing, nasal congestion, nasal itching and rhinorrhea. The eyes, ears, sinuses and throat can also be involved. Allergic rhinitis is the most common cause of rhinitis and while not a life-threatening condition, complications can occur and the condition can significantly impair quality of life.
The Role of Immune Mediators in Allergic Rhinitis
Allergic rhinitis involves inflammation of the mucous membranes of the nose, eyes, eustachian tubes, middle ear, sinuses and pharynx. This inflammation is characterized by a complex interaction of inflammatory mediators but ultimately is triggered by an immunoglobulin E (IgE)–mediated response to a foreign allergen. When a specific allergen (e.g., pollen) is inhaled into the nose, it can bind to the IgE on the mast cells, leading to immediate and delayed release of a number of mediators, the release of which can ultimately lead to the common allergic symptoms such as nasal congestion, sneezing, itching and rhinorrhea. These mediators include histamine, tryptase, chymase, kinins, heparin, leukotrienes and PGD2. PGD2 is the immune mediator most commonly associated with the chronic symptoms of allergic rhinitis.
How R112 Works and Its Possible Advantages
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 in an allergic attack, potentially making R112 a more effective and comprehensive drug. Currently, steroids are the major class of drugs that are able to block multiple mediators in the allergic response, but these have a comparatively slow onset of action. In the phase I/II trial, R112 began to diminish chemical mediator release within minutes after allergen challenge. R112 is delivered intra-nasally and no systemic exposure to R112 has been detected in any intra-nasal administration in any human trials conducted to date.