Delving into the Latest Updates on N-acetyl-D-mannosamine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

2-Actamido-2-deoxy-D-mannose, D-ManNAc, LB-301 - Leadiant Biosciences

+ [7]

Target-

Action

stimulants, modulators

Mechanism

Glycosylation stimulants, Proteins modulators

Therapeutic Areas

Nervous System DiseasesSkin and Musculoskeletal DiseasesUrogenital Diseases+ [1]

Active Indication

Glomerulosclerosis, Focal SegmentalDistal Myopathy, Nonaka Type

Inactive Indication

Glomerulonephritis, MembranousNephrosis, Lipoid

Originator Organization

National Institutes of Health

Active Organization

National Human Genome Research Institute

Leadiant Biosciences, Inc.

Inactive Organization

National Institute of Diabetes & Digestive & Kidney Diseases

License Organization

National Human Genome Research Institute

Leadiant Biosciences, Inc.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC8H15NO6

InChIKeyMBLBDJOUHNCFQT-WCTZXXKLSA-N

CAS Registry3615-17-6

Background:
Focal segmental glomerulosclerosis (FSGS) is a disease that causes scarring in parts of the kidneys that filter waste. This can lead to protein loss in the urine, which can worsen kidney function. The kidneys may fail over time, and dialysis or a kidney transplant may be needed. Other treatments for this disease do not always work and often have adverse effects. Better treatments for FSGS are needed.
Objective:
To test a study drug (ManNAc) in people with FSGS.
Eligibility:
People aged 18 years and older with FSGS.
Design:
Participants will have 5 to 6 clinic visits over 14 weeks. Two of the visits will require overnight stays for 2 or 3 nights.
ManNAc is a white powder that comes in a sachet. It is dissolved in water and taken twice a day by mouth. Participants will take their first dose at the clinic. They will learn how to store ManNAc and prepare each dose. They will record their doses in a diary. They will also write down any adverse effects or troubles they have using the drug at home.
During clinic visits, participants will have physical exams with blood and urine tests. They will complete questionnaires about their health, sleep habits, and fatigue symptoms.
During overnight visits, participants will also have 24-hour urine collection.
A study team member will call participants 1 week after the first dose to check on their health. Follow-up phone calls will then be every 2 weeks after each clinic visit.
Participants may meet with a dietitian to discuss nutrition while taking the ManNAc.
Participants may choose to have genetic tests.

Start Date05 Aug 2026

Sponsor / Collaborator

National Human Genome Research Institute

ACTRN12623000609651

/ RecruitingNot ApplicableIIT

An open-label, randomised, three-arm crossover study to examine the comparative pharmacokinetics of ManNAc administered as an oral solution and as two novel oral tablet formulations in healthy adult males

Start Date13 Jul 2023

Sponsor / Collaborator

University of South Australia

ACTRN12622000394741

/ CompletedNot ApplicableIIT

An open-label, randomised, two-arm crossover study to determine the absolute oral bioavailability of ManNAc in healthy adult males

Start Date17 Nov 2022

Sponsor / Collaborator

University of South Australia

100 Clinical Results associated with N-acetyl-D-mannosamine

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100 Translational Medicine associated with N-acetyl-D-mannosamine

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100 Patents (Medical) associated with N-acetyl-D-mannosamine

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979

Literatures (Medical) associated with N-acetyl-D-mannosamine

01 May 2026·Clinical Drug Investigation

Alternative Dosing Strategies to Enhance the Absorption of N-Acetyl-d-Mannosamine Monohydrate (ManNAc) in Healthy Adult Males

Article

Author: Evans, Allan M ; Wabnitz, Paul ; Condon, James ; La Fontaine, Kellie ; Fornasini, Gianfranco ; Meola, Tahlia R ; Reuter, Stephanie E

BACKGROUND:

GNE myopathy is a rare autosomal recessive muscle disease caused by biallelic mutations in GNE, a gene which encodes the bifunctional enzyme that catalyses the rate-limiting step of intracellular sialic acid biosynthesis. Whilst there is no current marketed therapy to treat the disease, current investigations focus on supplementation with N-acetyl-D-mannosamine monohydrate (ManNAc), a precursor in the biosynthesis of N-acetylneuraminic acid (Neu5Ac), the most abundant sialic acid. ManNAc possesses a low oral bioavailability, likely owing to poor absorption, and exhibits non-linearity across the therapeutic range, possibly due to saturation of intestinal transporter systems.

OBJECTIVES:

The study was conducted to examine if the absorption of ManNAc could be improved by administering a smaller (non-saturating) oral dose, more frequently, or by co-administering ManNAc with dietary salt, which might facilitate carrier-mediated transport.

METHODS:

This was an open-label, randomised, cross-over study in 12 healthy male participants. Participants were administered 4 x 1 g doses of ManNAc every hour, 4 g ManNAc as a single dose with 1 g dietary salt or 4 g ManNAc alone.

RESULTS:

The pharmacokinetic analysis population comprised 11 participants who received all three study treatments. Administration of ManNAc as split doses, more frequently, resulted in a 1.7-fold increase in ManNAc plasma exposure compared to a single 4 g dose, with a corresponding 1.9-fold increase in systemic Neu5Ac concentrations. In comparison, co-administration of ManNAc with dietary salt had no impact on ManNAc absorption.

CONCLUSIONS:

This study suggests that strategies to slow down the delivery of ManNAc to the small intestine may significantly improve its overall bioavailability and therefore reduce total daily dose requirements.

CLINICAL TRIAL REGISTRATION:

The clinical trial was registered on the Australian New Zealand Clinical Trials Registry (ID: ACTRN12620001127998).

01 Mar 2026·Kidney International Reports

Phase 1 Study of Oral N-Acetylmannosamine in Primary Podocytopathies

Article

Author: Ganguli, Anirban ; Rossignol, Francis ; Bolaños, Jonathan ; Figg, William D ; Leoyklang, Petcharat ; Kopp, Jeffrey B ; Gahl, William A ; Huizing, Marjan ; Zeng, Yi ; Wilkins, Kenneth J ; Malicdan, May Christine V

Introduction:

Terminal sialic acid (SA) residues on glycoconjugates are essential for maintaining the glomerular filtration barrier's charge selectivity and podocyte ultrastructure. SA depletion affects key podocyte glycoproteins, contributing to podocytopathy and proteinuria. Glomerular hyposialylation is commonly seen in experimental podocytopathies and human renal biopsies. In nephrotic mouse models, oral administration of the metabolic SA precursor, N-acetylmannosamine (ManNAc) restored sialylation and reduced proteinuria, suggesting therapeutic potential.

Methods:

In this single-center, single-arm, ascending dose phase 1 trial, we evaluated safety and pharmacokinetics (PKs) of oral ManNAc in primary podocytopathies (ClinicalTrials.gov: NCT02639260). Eligible participants had urine protein-to-creatinine ratio (UPCR) > 1 g/g and estimated glomerular filtration rates (eGFR) > 15 ml/min per 1.73 m². Six subjects received a single 3g ManNAc dose followed by 5 days of 1.5 g twice-daily (BID) dosing. One subject received a single 6 g dose.

Results:

All enrolled participants had primary podocytopathy, with eGFR of 25 to 89 ml/min per 1.73 m² and UPCR of 1.1 to 9.21 g/g. ManNAc was well-tolerated without serious adverse events (AEs). Maximum plasma ManNAc concentration was reached within 2 to 4 hours postdose, with dose-dependent increases in plasma SA. Subjects with eGFR < 45 ml/min per 1.73 m² showed elevated maximum plasma ManNAc concentration and area under curve for both ManNAc and SA, reflecting reduced renal clearance. Proteinuria reduction of 12% to 52% (regression-adjusted mean 9.69%, P < 0.0001) was observed in subjects receiving ManNAc BID, correlating with glomerular hyposialylation in pre-study renal biopsies.

Conclusion:

Oral ManNAc demonstrated short-term safety and increased plasma SA levels in podocytopathy subjects. Early efficacy signals suggest that proteinuria reduction may correlate with glomerular hyposialylation, identifying a potential treatment biomarker. A phase 2 trial (NCT06664814) is underway to assess long-term outcomes.

01 Feb 2026·BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Absolute bioavailability and intravenous pharmacokinetics of N‐acetyl‐D‐mannosamine in humans

Article

Author: Guy Ludbrook ; Allan M. Evans ; Gianfranco Fornasini ; Tahlia R. Meola ; Stephanie E. Reuter ; Olga Pavlova ; Sumit Jain

Aims:

N‐acetyl‐D‐mannosamine monohydrate (ManNAc) is a naturally occurring monosaccharide that has attracted considerable attention for its potential in treating GNE myopathy, a rare autosomal recessive muscle disorder. Despite its promise as an oral treatment, the absolute bioavailability of oral ManNAc has not been determined and there has been no evaluation of the ManNAc pharmacokinetics following intravenous administration in humans. The aim of this study was to investigate the pharmacokinetics of intravenous ManNAc and to characterize its absolute bioavailability following a single oral dose.

Methods:

In this single‐centre, open‐label, crossover study, six healthy adult males were administered ManNAc as a single oral dose (1000 mg) and intravenous dose (100 mg). Blood samples were collected over a 48 h period after dose administration for the quantification of plasma ManNAc concentrations. Non‐compartmental pharmacokinetic analysis was performed using baseline‐corrected plasma concentration–time data.

Results:

After intravenous dosing, the mean plasma clearance of ManNAc was 10.1 ± 1.94 L/h, volume of distribution was 24.1 ± 4.98 L and elimination half‐life was 1.67 ± 0.251 h. The mean absolute bioavailability of oral ManNAc at a dose of 1000 mg was 4.01 ± 1.82%. Deconvolution analysis revealed a zero‐order absorption rate of about 10 mg per hour in the initial 3 h after dosing.

Conclusions:

The low oral bioavailability of ManNAc is likely due to poor absorption (rather than first‐pass hepatic extraction) due to its high polarity. In addition, zero‐order absorption explains why the systemic exposure to ManNAc does not increase proportionally with dose.

100 Deals associated with N-acetyl-D-mannosamine

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glomerulosclerosis, Focal Segmental	Phase 2	United States	National Human Genome Research Institute	05 Aug 2026
Distal Myopathy, Nonaka Type	Phase 2	United States	National Human Genome Research Institute	05 Feb 2015
Glomerulonephritis, Membranous	Phase 1	United States	National Institute of Diabetes & Digestive & Kidney Diseases	07 Jul 2016
Nephrosis, Lipoid	Phase 1	United States	National Institute of Diabetes & Digestive & Kidney Diseases	07 Jul 2016

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02346461 (Pubmed \| Genet Med) Manual	Phase 2	Distal Myopathy, Nonaka Type	12	ManNAc	neoxzrpaxz(dplssmlykk) = dbduqukyis utynolxzyc (egnufikget )	Positive	01 Nov 2021
NCT02639260 (Phase 1 Study of N-Acetylmannosamine (ManNAc) for Glomerular Disease, ASN2020)	Phase 1	Glomerular disease	7	ManNAc 3g single dose	mpczlhefut(iapfdbjnyp) = There were no serious adverse events. Most subjects (5 of 6) that received ManNAc twice daily showed a marked reduction in urine PCR (26-54%), which correlated with the degree of glomerular hyposialylation lmqonvjwfd (riyiiuazwr ) View more	Positive	19 Oct 2020
NCT02346461 (CTgov)	Phase 2	Distal Myopathy, Nonaka Type	12	ManNAc (ManNAc: Cohort A)	hknltxyxao(qrjgnhxush) = dxtsmedrsn lybkwgsomd (xnbdlyrlka, 1776) View more	-	16 Apr 2019
NCT02346461 (CTgov)	Phase 2	Distal Myopathy, Nonaka Type	12	ManNAc (ManNAc: Cohort B)	hknltxyxao(qrjgnhxush) = rtvssjtzpm lybkwgsomd (xnbdlyrlka, 2710) View more	-	16 Apr 2019