ACER-001 for Urea Cycle Disorders (UCDs)

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ACER-001 is a fully taste-masked, immediate-release formulation of sodium phenylbutyrate (NaPB) developed using a microencapsulation process. NaPB has been found to help control blood ammonia levels in conjunction with a restricted diet for people with a urea cycle disorder (UCD).1,2 However, non-compliance with treatment is common. Reasons given for non-compliance include the unpleasant taste associated with available medications, the frequency with which medication must be taken and the high cost of the medication.

For the treatment of UCD, NaPB is a prodrug that metabolizes quickly to become phenylacetate. Phenylacetate then binds to glutamine via acetylation to become phenylacetylglutamine. Phenylacetylglutamine is similar to urea in that it contains two moles of nitrogen and is excreted by the kidneys. Through this process, NaPB is an alternate way to excrete excessive nitrogen created by ineffective processing of ammonia during the urea cycle.4


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We believe that if ACER-001 is approved, its taste-masked properties will make it a compelling alternative to existing NaPB-based treatments, as the unpleasant taste associated with NaPB is cited as a major impediment to patient compliance with those treatments. 3 In October 2019, we announced full enrollment of Part A in an ongoing pivotal trial evaluating bioavailability and bioequivalence of ACER-001 for the treatment of UCDs. The ACER-001 trial design consists of two parts. Part A is a single-center, single-blind, randomized, single-dose crossover trial designed to evaluate the relative bioavailability of three different oral suspension formulations of ACER-001 compared to BUPHENYL® in 20 healthy adult subjects. The goal of Part A of this study is to provide data to help identify the optimal formulation of ACER-001 for further evaluation in Part B.  Part B will be a single-center, open-label, randomized, single-dose crossover trial to demonstrate bioequivalence of the optimal formulation of ACER-001 compared to BUPHENYL® in 36 healthy adult subjects.

References

  1. Ah Mew N, Lanpher BC, Gropman A, Chapman KA, al. e. Urea cycle disorders overview. Gene Reviews. Seattle, Washington: University of Washington, Seattle; 1993.
  2. Sirrs SM, et al. Barriers to Transplantation in Adults with Inborn Errors of Metabolism. JIMD Rep. 2013;8:139-144.
  3. Camp KM, et al. Phenylketonuria Scientific Review Conference: State of the science and future research needs. Mol Genet Metab. 2014;112(2):87-122.
  4. Shchelochkov OA,et al. Barriers to drug adherence in the treatment of urea cycle disorders: Assessment of patient, caregiver and provider perspectives. Mol Genet Metab. 2016;8:43-47.
  5. Brusilow SW, Maestri NE. Urea cycle disorders: diagnosis, pathophysiology, and therapy. Adv Pediatr. 1996;43:127-170.
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