New results from BioCryst's BCX4208 Phase 2b gout study

Nov 8 2011

BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) presents new results from its Phase 2b randomized, double-blind, dose-response study of BCX4208 in patients with gout who have failed to reach the clinically important serum uric acid (sUA) goal of <6 mg/dL on allopurinol alone. The results were accepted as a late-breaking oral presentation titled "BCX4208 Combined With Allopurinol Increases Response Rates in Patients With Gout Who Fail to Reach Goal Range Serum Urate on Allopurinol Alone: A Randomized, Double-Blind, Placebo-Controlled Trial" at the 2011 American College of Rheumatology and the Association of Rheumatology Health Professionals (ACR/ARHP) Annual Scientific Meeting. The presentation will take place from 2:30-4:30 p.m. Central Time (Presentation Number L10; W375c (McCormick Place West)).

This Phase 2b study randomized 279 patients to five study arms: BCX4208 at doses of 5 mg, 10 mg, 20 mg, 40 mg and placebo, administered once-daily for 12-weeks. Allopurinol 300 mg once-daily was administered in all study arms. The primary study endpoint was the proportion of patients with sUA <6 mg/dL at day 85. The mean baseline sUA for the randomized population was 6.9 mg/dL.

The primary endpoint of the study was successfully achieved. When added to allopurinol 300 mg, BCX4208 was superior to allopurinol plus placebo>

"This important study demonstrates that low doses of BCX4208 combined with allopurinol safely and significantly increase the proportion of patients reaching therapeutic goal compared to 300 mg allopurinol, the most commonly prescribed dose in the U.S. The study population was representative of the general gout population, and included patients with mild renal impairment, kidney stones and other co-morbidities," said lead investigator for the study, Michael Becker, M.D., Professor Emeritus of Medicine, University of Chicago. "These encouraging safety and efficacy results support the continued development of BCX4208 added to xanthine oxidase inhibitors such as allopurinol, and the advancement of BCX4208 into Phase 3 studies."

The frequency and types of adverse events, including infections, were similar between the groups treated with BCX4208 and placebo. No opportunistic or unusual infections were reported in either the BCX4208 treated groups or placebo. A dose-dependent decrease in lymphocytes was observed, which reached a plateau between day 57 and 85 for patients still remaining in the study. The frequency of confirmed gout flares was low, ranging from 5% to 11% for BCX4208 doses combined with allopurinol, compared to 5% for placebo plus allopurinol.

BioCryst also presented results from other BCX4208 clinical and pre-clinical studies at a poster session on Monday, November 7, 2011. The two posters presented were:

• Presentation Number 1018: "BCX4208 Synergistically Lowers sUA Levels when Combined with Allopurinol in Patients with Gout: Results of a Phase 2 Dose-Ranging Trial" concluded that synergistic mean and percent reductions in sUA level were observed with BCX4208 combined with allopurinol. BCX4208 plus allopurinol 300 mg brought 75% to 100% of gout patients to target sUA level versus 40% for allopurinol 300 mg alone. This combination was generally safe and well-tolerated, with diarrhea and headache as the most commonly reported adverse events
• Presentation Number 1026: "Nonclinical Drug-Drug Interaction (DDI) Profile of BCX4208, an Oral, Once-Daily, Novel Nonmetabolized Enzyme Inhibitor for Chronic Management of Gout" concluded that the potential for hepatic or renal DDIs is low given that BCX4208 does not induce or inhibit CYP isoforms, has low potential as a P-gp substrate or inducer, and is not a substrate or inhibitor of renal organic anion and cation transporters. Furthermore, BCX4208 undergoes renal elimination and is not metabolized by liver cells.