Chemistry:Seliforant
Seliforant (also known as SENS-111 or UR-63325) is an investigational small-molecule drug developed by Sensorion (originally by Palau Pharma) for inner-ear/vestibular disorders, particularly vertigo and vestibular neuritis, and has also been cited as having potential for tinnitus and hearing loss indications.[1]
Background and development
Seliforant was first developed as a first-in-class antagonist of the histamine H4 receptor (H4R), a receptor subtype implicated in immune modulation and potentially neurosensory signalling.[2]
The drug was granted its International Non-Proprietary Name (INN) "seliforant" by the World Health Organization in 2018.[1]
Mechanism of action
Seliforant functions by antagonising the histamine H4 receptor (H4R).[2] H4 receptors are expressed in several tissues including immune cells and may play roles in neurosensory signalling. The rationale for vestibular/ear indications is based on modulation of aberrant vestibular/inner-ear neuronal activity rather than conventional antihistamine pathways.[3]
Clinical trials and status
Vestibular disorders
- A Phase 2 proof-of-concept trial (NCT03110458 / EudraCT 2016–003927–45) of seliforant in acute unilateral vestibulopathy was completed, but seliforant did not meet its primary efficacy endpoint.[4]
- Earlier Phase 2a trials in healthy volunteers assessing tolerability and pharmacodynamics reported that seliforant met tolerability endpoints (no sedation from anticholinergic effects) but efficacy in patients remains unsupported.[5]
Safety
In human Phase 1/2 volunteer studies, seliforant was reported to be well tolerated, with mild to moderate events and no sedation reported.[5]
See also
References
- ↑ 1.0 1.1 "World Health Organization Grants Name 'Seliforant' to Sensorion's SENS-111 Treatment". 2018-05-03. https://www.santelog.com/actualites-sante-nasdaq/world-health-organization-grants-name-seliforant-sensorions-sens-111.
- ↑ 2.0 2.1 "Seliforant (SENS-111) – Sensorion". https://adisinsight.springer.com/drugs/800031434.
- ↑ "Effect of the novel histamine H4 receptor antagonist SENS-111 on spontaneous nystagmus in a rat model of acute unilateral vestibular loss". British Journal of Pharmacology 177 (3): 623–633. February 2020. doi:10.1111/bph.14803. PMID 31347148.
- ↑ "Sensorion Scuttles SENS-111 Vestibulopathy Drug to Focus on Sudden Hearing Loss". 2019-12-03. https://hearingreview.com/inside-hearing/research/sensorion-scuttles-sens-111-vestibulopathy-drug-to-focus-on-sudden-hearing-loss.
- ↑ 5.0 5.1 "Safety, tolerability, pharmacokinetics and pharmacokinetic-pharmacodynamic modelling of the novel H4 receptor inhibitor SENS-111 using a modified caloric test in healthy subjects". British Journal of Clinical Pharmacology 84 (12): 2836–2848. December 2018. doi:10.1111/bcp.13744. PMID 30152527.
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