SAFETY AND EFFICACY OF ALLN-346 ORAL ENZYME THERAPY IN PATIENTS WITH HYPERURICEMIA AND CHRONIC KIDNEY DISEASE (CKD): RESULTS OF THE PHASE 2A STUDY
Authors: Terkeltaub R et al., USA
In this phase 2A Study a new oral therapy with ALLN346 for gout was examined to assess the safety, tolerability and bioactivity in adults with hyperuricemia and CKD. ALLN-346 (engineered urate oxidase) is a urate specific enzyme, designed to enhance degradation and secretion of urate in the intestinal tract and therefore this drug is independent of kidney function.
In this one-week inpatient phase 2 A study 11 otherwise healthy adult patients with hyperuricemia (sUA ≥ 6.8mg/dL) and normal to stage 2 CKD were included and randomized (2:1) to receive either 5 capsules of ALLN-346 or matching placebo three times daily for 7 days. A statistically significant reduction in mean serum uric acid (sUA) was recorded with ALLN-346 compared to placebo. The largest mean % reduction in sUA was observed among patients with stage 2 CKD; sUA reduction was correlated with eGFR in the ALLN-346 group but not the placebo group. No serious adverse events were reported.
In this study, oral therapy with ALLN-346 for 7 days was well tolerated and resulted in a significant reduction in sUA. Consistent with the known pathophysiologic adaptation of increased intestinal elimination of uric acid in patients with impaired kidney function and the intestinal-based mechanism of action of ALLN-346, there was a strong correlation between the effect of ALLN346 on sUA reduction and the level of kidney function. The generated data support proof of pharmacology for the intestinal mechanism of action of ALLN-346 to degrade urate either formed or secreted in the gut. Future studies in the larger gout population with CKD are underway.