A phase 1b randomised clinical trial evaluating BBI-001, a non-absorbed oral therapeutic for the treatment of iron overload

Abstract Non-transfusion-dependent iron overload is the result of excessive dietary iron absorption, most commonly caused in populations of European descent by the genetic disorder HFE-related hemochromatosis (HH). In this disorder, hyperabsorption of 3–5 mg of iron per day cannot be counterbalanced...

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Main Authors: Curtis Scribner, Jamie Cope, Philip Ryan, John K. Olynyk, John Ryan, J. Daniel Griffin, Cory Berkland
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-01421-4
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author Curtis Scribner
Jamie Cope
Philip Ryan
John K. Olynyk
John Ryan
J. Daniel Griffin
Cory Berkland
author_facet Curtis Scribner
Jamie Cope
Philip Ryan
John K. Olynyk
John Ryan
J. Daniel Griffin
Cory Berkland
author_sort Curtis Scribner
collection DOAJ
description Abstract Non-transfusion-dependent iron overload is the result of excessive dietary iron absorption, most commonly caused in populations of European descent by the genetic disorder HFE-related hemochromatosis (HH). In this disorder, hyperabsorption of 3–5 mg of iron per day cannot be counterbalanced by the typical passive elimination of 1–2 mg of iron each day into the feces by the shedding of enterocytes. Therefore, the current standard of care for most HH individuals who develop iron overload is to undergo systemic iron reduction with induction-phase phlebotomy therapy followed by long-term maintenance phlebotomy therapy. Unfortunately, long-term compliance with a regular phlebotomy regimen is less than 25% in some clinical settings. BBI-001 is a non-absorbed, oral therapeutic that binds dietary iron in the gut, preventing absorption and promoting iron elimination in the feces. The safety and efficacy of BBI-001 was confirmed in a single ascending dose, double-blind, Phase 1b clinical trial NCT05238207 (14/02/2022) in patients with iron deficiency. No treatment-related adverse events occurred for single doses of up to 2000 mg of BBI-001. The study also established proof-of-mechanism since BBI-001 significantly reduced the absorption of iron isotopes from breakfast meals compared to placebo. BBI-001 was most effective in subjects who hyperabsorbed iron (> 3 mg) on placebo, suggesting an ability to normalize iron absorption in at-risk patients. This study supports the further evaluation of BBI-001 as a safe pharmaceutical alternative to lifelong therapeutic phlebotomy.
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spelling doaj-art-0b04de54e0d843f090d6bac767aa0c8e2025-08-20T03:53:57ZengNature PortfolioScientific Reports2045-23222025-05-011511810.1038/s41598-025-01421-4A phase 1b randomised clinical trial evaluating BBI-001, a non-absorbed oral therapeutic for the treatment of iron overloadCurtis Scribner0Jamie Cope1Philip Ryan2John K. Olynyk3John Ryan4J. Daniel Griffin5Cory Berkland6Bond Biosciences, Inc.POG Consulting, Inc.Nucleus NetworkCurtin Medical School, Curtin UniversityHepatology Unit, Beaumont Hospital/RCSI University of Medicine and Health SciencesBond Biosciences, Inc.Bond Biosciences, Inc.Abstract Non-transfusion-dependent iron overload is the result of excessive dietary iron absorption, most commonly caused in populations of European descent by the genetic disorder HFE-related hemochromatosis (HH). In this disorder, hyperabsorption of 3–5 mg of iron per day cannot be counterbalanced by the typical passive elimination of 1–2 mg of iron each day into the feces by the shedding of enterocytes. Therefore, the current standard of care for most HH individuals who develop iron overload is to undergo systemic iron reduction with induction-phase phlebotomy therapy followed by long-term maintenance phlebotomy therapy. Unfortunately, long-term compliance with a regular phlebotomy regimen is less than 25% in some clinical settings. BBI-001 is a non-absorbed, oral therapeutic that binds dietary iron in the gut, preventing absorption and promoting iron elimination in the feces. The safety and efficacy of BBI-001 was confirmed in a single ascending dose, double-blind, Phase 1b clinical trial NCT05238207 (14/02/2022) in patients with iron deficiency. No treatment-related adverse events occurred for single doses of up to 2000 mg of BBI-001. The study also established proof-of-mechanism since BBI-001 significantly reduced the absorption of iron isotopes from breakfast meals compared to placebo. BBI-001 was most effective in subjects who hyperabsorbed iron (> 3 mg) on placebo, suggesting an ability to normalize iron absorption in at-risk patients. This study supports the further evaluation of BBI-001 as a safe pharmaceutical alternative to lifelong therapeutic phlebotomy.https://doi.org/10.1038/s41598-025-01421-4
spellingShingle Curtis Scribner
Jamie Cope
Philip Ryan
John K. Olynyk
John Ryan
J. Daniel Griffin
Cory Berkland
A phase 1b randomised clinical trial evaluating BBI-001, a non-absorbed oral therapeutic for the treatment of iron overload
Scientific Reports
title A phase 1b randomised clinical trial evaluating BBI-001, a non-absorbed oral therapeutic for the treatment of iron overload
title_full A phase 1b randomised clinical trial evaluating BBI-001, a non-absorbed oral therapeutic for the treatment of iron overload
title_fullStr A phase 1b randomised clinical trial evaluating BBI-001, a non-absorbed oral therapeutic for the treatment of iron overload
title_full_unstemmed A phase 1b randomised clinical trial evaluating BBI-001, a non-absorbed oral therapeutic for the treatment of iron overload
title_short A phase 1b randomised clinical trial evaluating BBI-001, a non-absorbed oral therapeutic for the treatment of iron overload
title_sort phase 1b randomised clinical trial evaluating bbi 001 a non absorbed oral therapeutic for the treatment of iron overload
url https://doi.org/10.1038/s41598-025-01421-4
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