Delving into the Latest Updates on Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences) with Synapse

Overview

Basic Info

Drug Type

Mesenchymal stem cell therapy

Synonyms

HHALPC, HepaStem, Heterologous Human Adult Liver derived Progenitor Cells

+ [1]

Target-

Mechanism

Cartilage replacements, Cell replacements, Osteogenesis stimulants

+ [1]

Therapeutic Areas

Digestive System DisordersNeoplasms

Active Indication

Liver CirrhosisNeoplasms

Inactive Indication

Citrullinemialiver function failureN-Acetyl Glutamate Synthetase Deficiency+ [3]

Originator Organization

Facultés Universitaires Catholiques de Mons

Active Organization

PROMETHERA Biosciences SA

Inactive Organization-

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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This is an interventional, double blind, randomized (2:1), and placebo-controlled study of 2 infusions of a 1 dose regimen of HepaStem in patients recently diagnosed (≤1 week) with ACLF grade 1 or 2 on top of Standard of Care (SoC), and for whom the diagnosis is not resolved on the day of infusion.

Start Date21 Jan 2020

Sponsor / Collaborator

Cellaïon SA

100 Clinical Results associated with Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences)

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100 Translational Medicine associated with Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences)

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100 Patents (Medical) associated with Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences)

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4

Literatures (Medical) associated with Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences)

01 Aug 2021·JHEP Reports

A phase II study of human allogeneic liver-derived progenitor cell therapy for acute-on-chronic liver failure and acute decompensation

Article

Author: Albillos, Agustin ; Sokal, Etienne M ; Lasser, Luc L ; Gustot, Thierry ; Vainilovich, Yelena ; Michel, Sébastien ; Najimi, Mustapha ; Stoykov, Ivaylo ; Lyubomirova, Desislava ; Gordillo, Noelia ; Nevens, Frederik ; Vargas, Victor ; Clerget-Chossat, Nathalie ; Haralampiev, Lyudmil E ; Laterre, Pierre-François ; Barthel, Virginie

BACKGROUND & AIMSHuman allogeneic liver-derived progenitor cells (HALPC, HepaStem®; Promethera Biosciences, Mont-Saint-Guibert, Belgium) are an advanced therapy medicinal product that could potentially alleviate systemic inflammation and ameliorate liver function in patients with acute-on-chronic liver failure (ACLF) or acute decompensation of cirrhosis (AD).METHODSThis open-label phase II study was conducted in 9 centres in Belgium, Spain, and Bulgaria between 2016 and 2019. The primary objective was to assess the safety of HALPC therapy up to Day 28 and the secondary objectives were to assess its safety and preliminary efficacy up to Month 3.RESULTSThe 24 treated patients (mean age: 51 years) were mostly male with an alcoholic cirrhosis. On pre-infusion Day 1, 15 patients had ACLF and 9 patients had AD. Two of the 3 initial patients treated with high HALPC doses (∼5×10⁶ cells/kg body weight [BW]) had severe adverse bleeding events attributed to treatment. In 21 patients subsequently treated with lower HALPC doses (0.6 or 1.2×10⁶ cells/kg BW, 1 or 2 times 7 days apart), no serious adverse events were related to treatment, and the other adverse events were in line with those expected in patients with ACLF and AD. Overall, markers of systemic inflammation and altered liver function decreased gradually for the surviving patients. The Day-28 and Month-3 survival rates were 83% (20/24) and 71% (17/24), and at Month 3, no patient had ACLF.CONCLUSIONSThe treatment of patients with ACLF or AD with up to 2 doses of 1.2×10⁶ HALPC/kg BW appeared safe. The results of this study support the initiation of a proof-of-concept study in a larger cohort of patients with ACLF to further confirm the safety and evaluate the efficacy of HALPC therapy.CLINICAL TRIALS REGISTRATIONEudraCT 2016-001177-32.LAY SUMMARYPatients with liver cirrhosis may suffer from the rapid onset of organ failure or multiple organ failure associated with a high risk of death in the short term. This clinical study of 24 patients suggests that an advanced therapy based on the intravenous infusion of low doses of human allogeneic liver-derived progenitor cells is safe and supports the next phase of clinical development of this type of therapy.

01 Dec 2020·Stem Cell Research & TherapyQ2 · MEDICINE

Infusion-related thrombogenesis by liver-derived mesenchymal stem cells controlled by anticoagulant drugs in 11 patients with liver-based metabolic disorders

Q2 · MEDICINE

ArticleOA

Author: Stéphenne, Xavier ; Sokal, Etienne E M ; Coppin, Louise C F ; Ambroise, Jérome ; Smets, Françoise

AbstractBackgroundMesenchymal stem cell (MSC) transplantation is a fast-developing therapy in regenerative medicine. However, some concerns have been raised regarding their safety and the infusion-related pro-coagulant activity. The aim of this study is to analyze the induced thrombogenic risk and the safety of adding anticoagulants during intraportal infusions of liver-derived MSCs (HepaStem), in patients with Crigler-Najjar (CN) and urea cycle disorders (UCD).MethodsEleven patients (6 CN and 5 UCD patients) were included in this partially randomized phase 1/2 study. Three cell doses of HepaStem were investigated: low (12.5 × 106 cells/kg), intermediate (50 × 106 cells/kg), and high doses (200 × 106 cells/kg). A combination of anticoagulants, heparin (10 I.U./5 × 106cells), and bivalirudin (1.75 mg/kg/h) were added during cell infusions. The infusion-related thrombogenic risk and anticoagulation were evaluated by clinical monitoring, blood sampling (platelet and D-dimer levels, activated clotting time, etc.) and liver Doppler ultrasound. Mixed effects linear regression models were used to assess statistically significant differences.ResultsOne patient presented a thrombogenic event such as a partial portal vein thrombus after 6 infusions. Minor adverse effects such as petechiae, epistaxis, and cutaneous hemorrhage at the site of catheter placement were observed in four patients. A significant decrease in platelet and increase in D-dimer levels were observed at the end of the infusion cycle, normalizing spontaneously after 7 days. No significant and clinically relevant increase in portal vein pressure could be observed once the infusion cycle was completed.ConclusionsThe safety- and the infusion-related pro-coagulant activity remains a concern in MSC transplantation. In our study, a combination of heparin and bivalirudin was added to prevent the thrombogenic risk induced by HepaStem infusions in 11 patients. A significant decrease in platelet and increase in D-dimer levels were observed, suggesting the activation of coagulation in these patients; however, this was spontaneously reversible in time. We can conclude that adding this combination of anticoagulants is safe and limits infusion-related thrombogenesis to subclinical signs in most of the patients.Trial registrationClinicalTrials.gov identifier: NCT01765283—January 10, 2013

01 Sep 2019·TransplantationQ2 · MEDICINE

Phase I/II Trial of Liver–derived Mesenchymal Stem Cells in Pediatric Liver–based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients

Q2 · MEDICINE

Article

Author: Grunewald, Stephanie ; Binda, Maria Mercedes ; McKiernan, Patrick ; Clapuyt, Philippe ; Belmonte, Nathalie ; de Vos, Beatrice ; Mandel, Hanna ; Kamińska, Diana ; Smets, Françoise ; Gonçalves, Isabel ; Dobbelaere, Dries ; Gissen, Paul ; Lopes, Ana Isabel ; Torre, Giuliano ; Najimi, Mustapha ; Pawlowska, Joanna ; Eyskens, François ; Yudkoff, Marc ; Thonnard, Joelle ; Pariente, Danièle ; Jacquemin, Emmanuel ; Sokal, Etienne ; Shteyer, Eyal ; Shapiro, Riki ; Dionisi-Vici, Carlo ; Broué, Pierre

Background.Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases.Objective.This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy.Methods.Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti–human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis.Results.The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases.Conclusions.This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses.

100 Deals associated with Mesenchymal stem cell therapy (HepaStem) (Promethera Biosciences)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
liver function failure	Discovery	ES	PROMETHERA Biosciences SA	30 Mar 2016
liver function failure	Discovery	BG	PROMETHERA Biosciences SA	30 Mar 2016
Ornithine Carbamoyltransferase Deficiency Disease	Discovery	BE	PROMETHERA Biosciences SA	01 Jul 2014
Ornithine Carbamoyltransferase Deficiency Disease	Discovery	FR	PROMETHERA Biosciences SA	01 Jul 2014
Urea Cycle Disorders, Inborn	Discovery	PT	PROMETHERA Biosciences SA	19 Mar 2013
Citrullinemia	Discovery	BE	PROMETHERA Biosciences SA	30 Nov 2012
Citrullinemia	Discovery	GB	PROMETHERA Biosciences SA	30 Nov 2012
Citrullinemia	Discovery	FR	PROMETHERA Biosciences SA	30 Nov 2012
N-Acetyl Glutamate Synthetase Deficiency	Discovery	BE	PROMETHERA Biosciences SA	30 Nov 2012
N-Acetyl Glutamate Synthetase Deficiency	Discovery	GB	PROMETHERA Biosciences SA	30 Nov 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01765283 (HEP001, Pubmed \| Transplantation) Manual	Phase 1/2	Urea Cycle Disorders, Inborn \| Metabolic Diseases \| Crigler-Najjar Syndrome	20	HepaStem	(prapqadxll) = dcbppamren jpmzmsdhnj (uhfwedekuw ) View more	Positive	01 Sep 2019