Tetrahydrouridine (NDec)
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Product Information
Scientific name: Tetrahydrouridine (NDec)
Brand name: N/A
RESPONSIBLE: Novo Nordisk -
Clinical Trial/Study Information
Trial Name: ASCENT1
Code: NCT05405114
Phase: 2
Eligible patient diagnosis: SCD (adults) (age 18 and above)
No. of Patients enrolled: 96 [actual] (Last update: 27/03/2026)
Study Sites: 68 Sites per countryAnticipated completion date: July 2025
Scope of the Study / Aim: Efficacy and safety of once- or twice-weekly NDec to increase in HbF haemoglobin levels, reduce sickling and VOCs -
Regulatory Information
Status: Not Authorised
Additional notable points:- EMA: N/A
- FDA: N/A
- MHRA: N/A
Update: 30 June 2026
• NDec is an oral modified-release, fixed combination of tetrahydrouridine (THU) and decitabine designed to treat sickle cell disease (SCD). Decitabine directly increases fetal hemoglobin (HbF) by reactivating HbF gene expression, while THU prevents rapid decitabine degradation.
• ASCENT1 (NCT05405114) was a global phase 2 trial evaluating the efficacy and safety of once-weekly (QW) or weekly on two consecutive days (W2CD) NDec in adults with SCD. Patients with chronic transfusion therapy, hematopoietic growth factors, recent voxelotor, crizanlizumab, or L-glutamine use could not participate. Based on hydroxyurea (HU) use at screening, patients not treated with HU for ≥12 weeks (wks) entered the HU-inactive block; patients who were currently treated with stable dose HU entered the exploratory HU-active block.
Data presented at the EHA Annual Congress (11 – 14 June 2026) from the global phase 2 ASCENT1 clinical trial showed that:
– 160 patients were enrolled in the HU-inactive block, of which 19 received NDec once weekly (QW) and 20 twice weekly (W2CD). 21 patients were on placebo (PBO).
• 83% had HbSS genotype
• 13 patients discontinued the treatment early (3 QW; 8 W2CD; 2 PBO)
• Mean change of haemoglobin from baseline to week 24 was:
▪ Increase by 0.37 g/dL with NDec QW,
▪ Increase by 0.97 g/dL with NDec W2CD
• A lower estimated annual VOC rate was observed with NDec W2CD
• Treatment-emergent adverse events (AEs) were more frequent with NDec W2CD vs NDec QW. 11 patients experienced neutropenia and 5 patients experienced thrombocytosis. All recovered after treatment
pause/discontinuation.
-19 patients were enrolled in the exploratory HU-active block of which 9 received NDec once weekly (QW) and 10 twice weekly (W2CD). 11 remained only on hydroxyurea (HU).
• An increase in %HbF was observed with NDec W2CD than HU at wks 24 and 48.
Update: 31 March 2026
No update available.
Update: 22 December 2025
No update available.
Update: 30 September 2025
No update available.
Update: 30 June 2025
No update available.
Update: 31 March 2025
No update available.
Update: 19 December 2024
No update available.
Update: 30 September 2024
No update available.
Update: 30 June 2024
No update available.
Update: 16 March 2024
No update available.
Update: 20 December 2023
No update available.
Update: 30 September 2023
No update available.
Update: 30 June 2023
No update available.
Update: 31 March 2023
No update available.
