Offices of Biotechnology and Business Development

More Promising Results from Dr. Vern Schramm’s Technology

Clinical trials for gout using second-generation Immucillins

A potential new treatment for gout is now in two parallel Phase 2 clinical trials. The first-generation Immucillins are currently in a late-stage pivotal clinical trial for cutaneous T-cell leukemia. A second-generation Immucillin called DADMe-ImmH (BCX4208) is another promising inhibitor for its target purine nucleoside phosphorylase and is now being developed for gout by BioCryst Pharmaceuticals, Inc.  

The Immucillins were discovered by the Schramm laboratory together with chemistry collaborators and co-inventors at Industrial Research Ltd. in New Zealand. The second-generation Immucillin used in clinical trials for gout is called BCX4208. This drug is showing promising results in human gout trials being conducted in the US.

Gout is a severe form of arthritis affecting tens of millions of people globally, a painful condition that is caused by deposits of uric acid in joints. Gout is typically asymmetric in presentation and commonly begins with an attack in the big toe. In later stages, sodium urate crystals can form in multiple joints.

BioCryst Pharmaceuticals has recently reported significant reductions in blood uric acid levels and no major safety issues after the completion of the study's first phase. The mechanism of action of BCX4208 is to inhibit the activity of human purine nucleoside phosphorylase, an enzyme whose activity is necessary for the formation of uric acid in humans.

In the first part of the randomized, double-blind study, three different doses of BCX4208 were administered to gout patients once a day for 21 days. All three doses of BCX4208 demonstrated a statistically significant reduction in uric acid blood levels compared to placebo at day 22. The drug candidate was generally safe and well-tolerated at the doses evaluated.

When serum uric acid is elevated above normal levels, the risk of gout increases. A high level of uric acid in the blood is a necessary precursor to gout. Although the results released by BioCryst are from relatively early stages in drug development, and there is more testing ahead, these results are exciting for Einstein and Industrial Research Ltd. Gout is associated with ageing and metabolic disease, and gout is increasing in incidence as population’s age and type-2 diabetes and metabolic disorders increase.

Clinical trial results showed reductions in peripheral blood lymphocytes in patients treated with BCX4208, but none of the treated subjects were stopped due to this reduction. Overall, the frequency of adverse events in each of the BCX4208 treatment groups was comparable to that observed in the placebo group. Part two of the study, designed to sequentially evaluate the safety and efficacy of up to three higher doses of BCX4208, is now under way.

BioCryst also announced on June 1, 2010 that it had initiated a Phase 2 study of BCX4208 alone and in combination with allopurinol in patients with gout. Allopurinol is drug approved for the treatment of excess uric acid in blood, which inhibits the enzyme xanthine oxidase. "We are pleased to initiate this Phase 2 study of BCX4208, a highly potent and selective PNP inhibitor, as it will help to determine whether the inhibition of xanthine oxidase and PNP together has additive or synergistic effects in reducing uric acid levels in patients with gout," said Dr. William P. Sheridan, Chief Medical Officer at BioCryst. "We expect to complete this study during 2010 and look forward to providing top-line data in the fourth quarter."

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