Evidence map›Paper›PMID 38407540›Full record

Trial reportClinical and translational science2024

LTA4H inhibitor LYS006: Clinical PK/PD and safety in a randomized phase I clinical trial.

Christian Loesche, Damien Picard, Benjamin Van Hoorick, Imelda Schuhmann, Petra Jäger, Kai Klein, Carole Schuhler, Gebhard Thoma, Christian Markert, Birk Poller and 5 more

Open access · goldAbstract readRandomized Controlled TrialClinical Trial, Phase I
In one paragraph

Trial report in Clinical and translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
2.9field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Trial
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 2 countries.

Christian LoescheTranslational Medicine, Novartis BioMedical Research, Novartis Pharma AG, Basel, Switzerland.ORCID 0000-0001-6505-0349
Damien PicardTranslational Medicine, Novartis BioMedical Research, Novartis Pharma AG, Basel, Switzerland.ORCID 0009-0005-9078-4535
Benjamin Van HoorickClinical Pharmacology Unit, SGS, Antwerp, Belgium.
Imelda SchuhmannBiomarker Development, Novartis BioMedical Research, Novartis Pharma AG, Basel, Switzerland.ORCID 0009-0000-6056-6397
Petra JägerImmunology Disease Area, Novartis BioMedical Research, Novartis Pharma AG, Basel, Switzerland.ORCID 0000-0002-9248-4086
Kai KleinPK Sciences, Novartis BioMedical Research, Novartis Pharma AG, Basel, Switzerland.ORCID 0000-0002-4980-067X
Carole SchuhlerEarly Development Analytics, Novartis Pharma AG, Basel, Switzerland.ORCID 0009-0008-9445-4447
Gebhard ThomaGlobal Discovery Chemistry, Novartis Biomedical Research, Novartis Pharma AG, Basel, Switzerland.ORCID 0000-0003-0467-331X
Christian MarkertGlobal Discovery Chemistry, Novartis Biomedical Research, Novartis Pharma AG, Basel, Switzerland.ORCID 0000-0003-1857-9885
Birk PollerPK Sciences, Novartis BioMedical Research, Novartis Pharma AG, Basel, Switzerland.ORCID 0000-0002-1181-7572
Natasa ZamurovicPreclinical Safety, Novartis BioMedical Research, Basel, Switzerland.ORCID 0009-0004-5550-2961
H Markus WeissPK Sciences, Novartis BioMedical Research, Novartis Pharma AG, Basel, Switzerland.ORCID 0000-0003-0280-4814
Heike OttoImmunology Disease Area, Novartis BioMedical Research, Novartis Pharma AG, Basel, Switzerland.ORCID 0000-0002-8179-0993
Martin FinkEarly Development Analytics, Novartis Pharma AG, Basel, Switzerland.ORCID 0009-0009-3757-1230
Till A RöhnImmunology Disease Area, Novartis BioMedical Research, Novartis Pharma AG, Basel, Switzerland.ORCID 0000-0002-2448-3110
Novartis (Switzerland) · CHSGS (Belgium) · BE

Funding

Novartis Pharma AG
6 · The paper itself

Abstract

LYS006 is a novel, highly potent and selective, new-generation leukotriene A4 hydrolase (LTA4H) inhibitor in clinical development for the treatment of neutrophil-driven inflammatory diseases. We describe the complex pharmacokinetic to pharmacodynamic (PD) relationship in blood, plasma, and skin of LYS006-treated nonclinical species and healthy human participants. In a randomized first in human study, participants were exposed to single ascending doses up to 100 mg and multiple ascending doses up to 80 mg b.i.d.. LYS006 showed rapid absorption, overall dose proportional plasma exposure and nonlinear blood to plasma distribution caused by saturable target binding. The compound efficiently inhibited LTB4 production in human blood and skin blister cells, leading to greater than 90% predose target inhibition from day 1 after treatment initiation at doses of 20 mg b.i.d. and above. Slow re-distribution from target expressing cells resulted in a long terminal half-life and a long-lasting PD effect in ex vivo stimulated blood and skin cells despite low plasma exposures. LYS006 was well-tolerated and demonstrated a favorable safety profile up to highest doses tested, without any dose-limiting toxicity. This supported further clinical development in phase II studies in predominantly neutrophil-driven inflammatory conditions, such as hidradenitis suppurativa, inflammatory acne, and ulcerative colitis.

Indexed as

Epoxide HydrolasesPlasmaHumansNeutrophilsSkinEpoxide Hydrolasesleukotriene A4 hydrolase

Identifiers

PMID38407540
PMCPMC10837484
OpenAlexW4391512785

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.