Axys Pharmaceuticals moves forward on Phase II results

Advancing ulcerative colitis drug APC 2059

Axys Pharmaceuticals Inc. (South San Francisco, CA) plans to move forward with its ulcerative colitis program for its APC 2059 agent based on results from an open-label Phase II study that showed "patient response and the achievement of certain clinical benefits." APC 2059 is a small molecule tryptase inhibitor delivered by subcutaneous injection.

Subjects of the Phase II study included male and female patients ranging in age from 18 to 70 years, with at least a six-month history of ulcerative colitis and recurrent symptoms for at least two weeks, plus a DAI score of between 6 and 11. DAI measures such parameters such as stool frequency, rectal bleeding, mucosal appearance by endoscopy and the physician's rating of disease activity. In this study, 20 mg of APC 2059 were delivered twice daily while patients continued oral aminosalicylate therapy.

Results:

• APC 2059 was safe and well tolerated.
  
• 51% of the evaluable patients had improvement indicated by a DAI reduction of at least 4.
  
• 68% of patients experienced a reduction in stool frequency.
  
• 68% had a reduction in rectal bleeding.
  
• 58% achieved "clinically significant benefit" as measured by the IGA.
  
• 30% achieved a DAI less than or equal to 3, of whom 81% maintained that response during the 2-week follow-up period.
  
• 3 patients (out of 56) withdrew from the study.

Said Paul J. Hastings, president and CEO of Axys. "The improvements seen in moderate to severe UC patients already maintained on the current standard of aminosalicylate therapy indicate that APC 2059 may offer additional benefit for patients who might otherwise resort to an acute course of steroid treatment."

Hastings added that the positive results of this study warrant continuation of the clinical program into placebo-controlled Phase IIb/III clinical trials to further define the product profile, including dosage form, duration and frequency. He noted that the anti-inflammatory mechanism of tryptase inhibitors demonstrated in Axys' previous clinical trials in asthma and in a number of animal models of inflammation indicate that this class of compounds may offer a viable alternative to steroid therapy for patients who may become refractory to standard treatment.

Background
Ulcerative colitis, like Crohn's Disease, is an inflammatory disease of the colon from which approximately one-half million patients suffer, with males and females affected equally. Symptoms include bloody diarrhea, fecal incontinence, abdominal pain, and weight loss.

Current therapies include 5-ASA (aminosalicylic acid), steroids, immunosuppressive agents such as cyclosporine and, most recently, anti-TNF-(alpha) therapeutics—all of which target intestinal inflammation.

APC 2059 is a second-generation molecule that inhibits tryptase, an enzyme that is found in mast cells. Research suggests that tryptase functions pathologically as a potent mediator of mast cell-related allergic inflammatory conditions. In the gastrointestinal tract, mast cell infiltration and tryptase activity have long been associated with several pathologies, including inflammatory bowel disease, caliginous colitis and gastrointestinal allergy. Significantly elevated tryptase secretion and enzyme activity have been measured relative to controls for ulcerative colitis. Taken together, these observations have suggested that ulcerative colitis may well be a mast cell and tryptase-mediated disease.

For more information, contact Paul J. Hastings of Axys at 650-829-1000.

With contribution by Angelo DePalma
Managing Editor, Drug Discovery Online and Pharmaceutical Online
Email: adepalma@vertical.net