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About PBH

3D pie chart showing the prevalence of PBH using concentric gray, teal, and orange circles.

About PBH

Symptomatic post-bariatric hypoglycemia (PBH) affects approximately 8% of people who have undergone bariatric surgery and is thought to be caused by an excessive glucagon-like peptide-1 (GLP-1) response leading to hypoglycemia and impaired quality of life.

Disease pathology and potential intervention

PBH occurs, on average, 1-3 years post-bariatric surgery. PBH can cause severe hypoglycemia associated with inadequate supply of glucose to the brain, known as neuroglycopenia. Clinical manifestations can include impaired cognition, loss of consciousness, and seizures. PBH is also associated with a high degree of disability that can result in major disruptions to independent living.1-6

PBH is believed to result from an excessive GLP-1 response. Avexitide is designed to bind to the GLP-1 receptor and inhibit the effects of excessive GLP-1 in PBH, mitigating hypoglycemia by decreasing insulin secretion and stabilizing blood glucose levels.

Prevalence of PBH and Amylyx program status

There are no approved therapies for PBH, which affects approximately 160,000 people in the U.S.4-7

Avexitide is an investigational, first-in-class GLP-1 receptor antagonist with FDA Breakthrough Therapy Designation and Orphan Drug Designation in hyperinsulinemic hypoglycemia, a condition characteristic of PBH. Avexitide has demonstrated highly statistically significant and clinically meaningful data with a well-tolerated safety profile across multiple clinical trials, with no discontinuations. In previous Phase 2 and Phase 2b studies in PBH, in 18 and 16 people respectively who had PBH following bariatric surgery, treatment with avexitide during a 28-day treatment period led to statistically significant reductions in hypoglycemic events with a well-tolerated safety profile, including no discontinuations.

Chart demonstrating that avexitide reduced daily rates of hypoglycemia by greater than 50% in 2 Phase 2 PBH clinical trials.

We expect to begin the pivotal Phase 3 LUCIDITY clinical trial for avexitide in PBH in Q1 2025 with data readout anticipated in 2026. LUCIDITY is designed to have similar inclusion and exclusion criteria to the previous Phase 2 trials of avexitide in PBH and to evaluate the FDA agreed upon primary outcome of hypoglycemic events.

  1. Hazlehurst, J. et al. Endocrine Connections. 2024;13(5), e230285. http://doi.org/10.1530/EC-23-0285.
  2. Ostrovosky, V. et al. NMCD. 2023;33(6),1197-1205. http://doi.org/10.1016/j.numecd.2023.02.012.
  3. Salehi, M. et al. The Journal of Clinical Endocrinology & Metabolism. 2018;03(8):2815–2826. http://doi.org/10.1210/jc.2018-00528.
  4. Craig, C. M. et al. The Journal of Clinical Endocrinology & Metabolism. 2021;106(8):e3235-e3248. http://doi.org/10.1210/clinem/dgab103.
  5. Estimate of Bariatric Surgery Numbers, 2011-2022 - American Society for Metabolic and Bariatric Surgery (asmbs.org). Accessed June 6, 2024.
  6. Raverdy V. et al. Annals of Surgery. 2016;264(5):878-885. http://doi.org/10.1097/SLA.0000000000001768.
  7. de Heide, L. J. M. et al. Diabetes, Obesity, & Metabolism. 2023;25:735-747. http://doi.org/10.1111/dom.14920.
  8. Lee, C. J. et al. Surgery for Obesity and Related Disorders. 2018;14(6):797-802. https://doi.org/10.1016/j.soard.2017.06.004.
  9. Brix, J. M. et al. Obesity Facts. 2019;12:397-406. https://doi.org/10.1159/000493735.
  10. Fischer, L. E. et al. Surgery for Obesity and Related Disorders. 2021;17(10):1787-1798. https://doi.org/10.1016/j.soard.2021.04.021.

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