Acer Therapeutics and Relief Therapeutics Announce ACER-001 IND Submission for the Treatment of Maple Syrup Urine Disease - Seite 2

The proposed initial Phase 2a, open-label dose-ranging trial is designed to evaluate the effect of different doses of ACER-001 (sodium phenylbutyrate) on blood leucine and other branched-chain amino acid (BCAA) levels in MSUD patients.

Rationale for ACER-001 Treatment in MSUD

Multiple investigational trials evaluating sodium phenylbutyrate in urea cycle disorder (UCD) patients suggest treatment with sodium phenylbutyrate is associated with selective reduction in BCAA despite adequate dietary protein intake.^1,2,3,4 Analysis of data from a longitudinal multicenter study of 553 UCD patients treated with sodium phenylbutyrate demonstrated that sodium phenylbutyrate decreased plasma BCAA in patients with UCDs and could serve as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism.²

Based on this clinical observation, investigators at Baylor College of Medicine explored the potential of sodium phenylbutyrate treatment to lower BCAA and corresponding branched-chain α-ketoacid (BCKA) levels in both healthy subjects and patients with MSUD. The investigators found that sodium phenylbutyrate, when dosed over three days, showed a statistically significant reduction of leucine in all three healthy subjects and in three out of the five MSUD patients who participated in the trial.⁵

In November 2020, study results evaluating the effect of sodium phenylbutyrate in the management of acute metabolic decompensation in pediatric MSUD patients (n=10) were published by investigators from Istanbul University-Cerrahpasa Medical Faculty in the peer-reviewed Journal of Pediatric Endocrinology and Metabolism showing a significant reduction in leucine levels in MSUD patients experiencing an acute attack.⁶ The results suggested that sodium phenylbutyrate could be safely administered in combination with emergency protocol using other active pharmaceuticals and may provide additional clinical benefit beyond emergency protocol alone.