Delving into the Latest Updates on Lexaptepid pegol with Synapse

Overview

Basic Info

Drug Type

Aptamers

Synonyms

NOX-H94

Target

Hepc

Action

inhibitors

Mechanism

Hepc inhibitors(Hepcidin inhibitors)

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesUrogenital Diseases+ [2]

Active Indication-

Inactive Indication

AnemiaChronic DiseaseEndotoxemia+ [3]

Originator Organization

TME Pharma NV

Active Organization-

Inactive Organization

TME Pharma NV

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

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Sequence Code 29557576

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Dialysis patients regularly suffer from anemia which may be caused by various contributing factors, alone or in combination, including blood loss, low erythropoietin and iron sequestration. In most patients, the anemia is responsive to treatment with erythropoietin or other erythropoiesis stimulating agents (ESA) alone or in combination with intravenous (i.v.) iron. In about 10% of patients however, the anaemia does not respond appropriately to this standard treatment and high to very high doses of ESA and i.v. iron are used to maintain acceptable hemoglobin concentrations. In these patients, hepcidin was identified as a causative factor leading to anemia of chronic disease with functional iron deficiency and ESA-hyporesponsiveness.
The Spiegelmer lexaptepid pegol (NOX-H94) offers a hepcidin-specific approach to the treatment of anemia of chronic disease. The safety and the activity of lexaptepid pegol are supported by data from healthy subjects and patients with multiple myeloma or lymphoma. The present study in dialysis patients with functional iron deficiency and ESA-hyporesponsiveness is conducted to demonstrate the safety of lexaptepid pegol in this population, to investigate its pharmacokinetic (PK) and pharmacodynamic (PD) profiles and its efficacy in increasing haemoglobin (Hb) in dialysis patients.

Start Date01 May 2014

Sponsor / Collaborator

TME Pharma NV

NCT01691040

/ CompletedPhase 2

Phase IIa Study to Characterize the Effects of the Spiegelmer® NOX H94 on Anemia of Chronic Disease in Patients With Cancer

This study is conducted to determine the safety, tolerability, and efficacy of NOX-H94 in patients with anemia of chronic disease (ACD). Furthermore, this study is intended to provide data needed to correlate plasma concentrations of NOX-H94 with its efficacy and to choose the appropriate dose and dose schedule of subsequent efficacy studies.
Some chronic diseases, e.g. tumors, inflammation, renal disease, are associated with high hepcidin concentrations in the blood. These hepcidin concentrations cause a reduction in iron concentrations in the blood and subsequently impair formation of red blood cells. Treatment with NOX-H94 is expected to inhibit this patho-mechanism by binding and inactivating hepcidin.

Start Date01 Sep 2012

Sponsor / Collaborator

TME Pharma NV

DRKS00003478

/ CompletedPhase 1

Randomized double blind placebo controlled PK/PD study on the effects of a single intravenous dose of NOX H94 on serum iron during experimental human endotoxemia

Start Date30 Jan 2012

Sponsor / Collaborator

NOXXON Pharma AG

100 Clinical Results associated with Lexaptepid pegol

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100 Translational Medicine associated with Lexaptepid pegol

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100 Patents (Medical) associated with Lexaptepid pegol

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3

Literatures (Medical) associated with Lexaptepid pegol

01 May 2016·British Journal of Pharmacology

Safety, pharmacokinetics and pharmacodynamics of the anti‐hepcidin Spiegelmer lexaptepid pegol in healthy subjects

Article

Author: Riecke, K ; Schwoebel, F ; Warrington, S ; Boyce, M ; Vauléon, S ; Zöllner, S ; Summo, L ; Cortezi, B ; Swinkels, D W

Background and Purpose:

Anaemia of chronic disease is characterized by impaired erythropoiesis due to functional iron deficiency, often caused by excessive hepcidin. Lexaptepid pegol, a pegylated structured l‐oligoribonucleotide, binds and inactivates hepcidin.

Experimental Approach:

We conducted a placebo‐controlled study on the safety, pharmacokinetics and pharmacodynamics of lexaptepid after single and repeated i.v. and s.c. administration to 64 healthy subjects at doses from 0.3 to 4.8 mg·kg−1.

Key Results:

After treatment with lexaptepid, serum iron concentration and transferrin increased dose‐dependently. Iron increased from approximately 20 μmol·L−1 at baseline by 67% at 8 h after i.v. infusion of 1.2 mg·kg−1 lexaptepid. The pharmacokinetics showed dose‐proportional increases in peak plasma concentrations and moderately over‐proportional increases in systemic exposure. Lexaptepid had no effect on hepcidin production or anti‐drug antibodies. Treatment with lexaptepid was generally safe and well tolerated, with mild and transient transaminase increases at doses ≥2.4 mg·kg−1 and with local injection site reactions after s.c. but not after i.v. administration.

Conclusions and Implications:

Lexaptepid pegol inhibited hepcidin and dose‐dependently raised serum iron and transferrin saturation. The compound is being further developed to treat anaemia of chronic disease.

01 Jan 2015·Drug discovery todayQ2 · MEDICINE

Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer® therapeutics

Q2 · MEDICINE

Review

Author: Vater, Axel ; Klussmann, Sven

Spiegelmers are synthetic target-binding oligonucleotides built from non-natural l-nucleotides. Like aptamers, Spiegelmers fold into distinct shapes that bind the targets with high affinity and selectivity. Furthermore, the mirror-image configuration confers plasma stability and immunological passivity. Various Spiegelmers against pharmacologically attractive targets were shown to be efficacious in animal models. Three Spiegelmer candidates: emapticap pegol (NOX-E36; anti-CCL2), olaptesed pegol (NOX-A12; anti-CXCL12) and lexaptepid pegol (NOX-H94; anti-hepcidin), underwent regulatory safety studies, demonstrated good safety profiles in healthy volunteers and were taken into Phase IIa studies in patients. Proof-of-concept for emapticap pegol has recently been demonstrated in diabetic nephropathy patients. Furthermore, promising interim Phase IIa data of olaptesed pegol and lexapteptid pegol also suggest efficacy in the respective patient populations.

23 Oct 2014·BloodQ1 · MEDICINE

Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans

Q1 · MEDICINE

Article

Author: Pickkers, Peter ; Kox, Matthijs ; van Eijk, Lucas T. ; Riecke, Kai ; John, Aaron S. E. ; van der Hoeven, Johannes G. ; Swinkels, Dorine W. ; Laarakkers, Coby M. ; Summo, Luciana ; Schwoebel, Frank ; Zöllner, Stefan ; Vauléon, Stéphanie

Key Points:

Lexaptepid modulates the inflammation-induced decrease in serum iron during experimental human endotoxemia. Hepcidin targeting with the novel compound lexaptepid may be a viable approach to the treatment of anemia of inflammation in humans.

100 Deals associated with Lexaptepid pegol

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12578

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Kidney Failure, Chronic	Phase 2	Germany	TME Pharma NV	01 May 2014
Kidney Failure, Chronic	Phase 2	Italy	TME Pharma NV	01 May 2014
Kidney Failure, Chronic	Phase 2	United Kingdom	TME Pharma NV	01 May 2014
Anemia	Phase 2	Austria	TME Pharma NV	01 Sep 2012
Anemia	Phase 2	Bulgaria	TME Pharma NV	01 Sep 2012
Anemia	Phase 2	Romania	TME Pharma NV	01 Sep 2012
Neoplasms	Phase 2	Austria	TME Pharma NV	01 Sep 2012
Neoplasms	Phase 2	Bulgaria	TME Pharma NV	01 Sep 2012
Neoplasms	Phase 2	Romania	TME Pharma NV	01 Sep 2012
Endotoxemia	Phase 1	Netherlands	TME Pharma NV	01 Jan 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01372137 (Pubmed \| Br J Pharmacol) Manual	Phase 1	Anemia	64	lexaptepid pegol	ixhafrpxij(nhjgvjchli) = Treatment with lexaptepid was generally safe and well tolerated, with mild and transient transaminase increases at doses ≥2.4 mg·kg(-1) and with local injection site reactions after s.c. but not after i.v. administration. naxwvfciyn (twfemteamj )	Positive	01 May 2016
				Placebo
ASN2015	Not Applicable	functional iron deficiency \| reticulocyte Hb \| soluble transferrin receptor	109	Lexaptepid Pegol	cejdkwinrg(yswyifbzph) = xcurgpwlhi xzyaggoizn (hagxywwmqn )	Positive	03 Nov 2015
FP660 (ERA2015)	Not Applicable	hepcidin \| iron \| TIBC ... View more	9	Lexaptepid 1.2 mg/kg	zqbdvpaecr(lshxvupeyf) = There were no treatment-related adverse events or other safety concerns in this study tearxizpiv (tsspzdvzpj ) View more	Positive	21 May 2015
				Placebo
NCT01691040 (AACR2014)	Phase 2	Chronic Lymphocytic Leukemia \| Multiple Myeloma \| Anemia in chronic kidney disease	12	Lexaptepid pegol (LP)	rdidsbsvqm(knkzvohofz) = ufwoovfowj tvzirqoomv (vfinnmwcoe ) View more	Positive	01 Oct 2014