New rhinitis therapy should help patients to breathe easy
SummaryRigel's new intranasal inhibitor R112 could offer a useful alternative therapy for patients suffering from allergic rhinitis, as Datamonitor's Shaun Falkingbridge explains. Bolstered by supportive recent trial results, Rigel can now go on to seek partner firms to realize full commercialization of the drug...
R112 is an intranasal inhibitor to SYK, or spleen tyrosine kinase, which is a novel drug target for respiratory diseases such as allergic rhinitis and asthma. SYK is involved in immunoglobulin E signaling in mast cells, which play important roles in both early and late phase allergic reactions. R112 is the most advanced compound in development with this mechanism of action for allergic rhinitis: a multidose safety trial of 24 patients conducted in 2003 indicated that R112 has a favorable safety profile, with no local nasal irritation and no significant laboratory abnormalities.
An alternative to corticosteroids needed
Last week, there was more upbeat news on R112 as Rigel reported results from the phase II trials. These studies took place in two locations in the where patients spent two days in an outdoor setting during the high pollen season. The newly reported data showed that treatment with R112 achieved a statistically significant improvement in Global Nasal Allergy Symptom Scores over placebo. Interestingly, symptoms associated with chronic nasal congestion were dramatically improved with R112 over the placebo group. This suggests the drug may address one unmet need in allergic rhinitis: that need being better, safer decongestants.
Given the non-fatal nature of allergic rhinitis, patients are unwilling to tolerate severe side effects and many physicians are reluctant to prescribe therapies that result in even minor side effects such as drowsiness. However, there is a real need for a safe and efficacious alternative to corticosteroid prophylactic therapy and, if successfully launched, R112 could represent the first alternative to intranasal corticosteroids in this market.
However, it may struggle in a market dominated on one side by oral antihistamines, and the other by intranasal steroids. Antihistamines are prescribed as first-line therapy as they are highly effective for the key symptoms of the disease. Patients that continue to suffer from symptoms may be prescribed an intranasal corticosteroid. Rigel could therefore position the drug as an add-on therapy in patients who are poorly controlled on intranasal steroids. However, greater commercial success may come from targeting patients who are not adequately managed with antihistamines alone, but do not need or want intranasal corticosteroids. The non-steroidal nature of the drug could be especially appealing for children with allergic rhinitis.
Partnership may be the way ahead
Rigel's business model is to develop product candidates through Phase II clinical trials, after which it seeks partners for completion of clinical trials, regulatory approval and marketing. Rigel is likely to want to partner with an established major pharmaceutical player in this market, such as GSK, Aventis, Pfizer or Schering-Plough. Rigel's problem is that some of the companies that could make the best partners, based on current market share, already have strategies to maintain and strengthen the current gold standards - for example, GSK and Aventis are both developing novel intranasal steroids.
Rigel may have to demonstrate how the drug could be positioned to complement the current gold standard therapies. For example, in clinical practice, if the clinician is faced with treatment of a patient already severely symptomatic with marked nasal congestion, R112 could perhaps be prescribed with an intranasal steroid. R112 would address the nasal congestion, allowing the steroid to exert an effect on the involved nasal mucosa.
The company could also convince potential partners that the mechanism of action could be useful for treating asthma. GSK and Aventis both confirm the efficacy of new respiratory drugs in asthma initially, followed later by the allergic rhinitis indication. Rigel has taken the opposite route: its next generation SYK inhibitors are anticipated to enter clinical trials for asthma in late 2004.
Rigel's strength is that it has a product with a truly novel mechanism of action, in a market with relatively little innovation - especially in comparison to other respiratory diseases such as asthma. Of all the companies currently in the allergic rhinitis market, Aventis appears to be the most likely company to take an interest this product. Aventis no longer has any R&D capability in this area, and has an active history of licensing novel respiratory products from the biotech industry.