Date: 2013-11-12
Type of information:
phase: 1-2
Announcement: completion of patient enrolment
Company: Promethera Biosciences (Belgium)
Product: Hepastem®
Action mechanism: Promethera® HepaStem is a cell-based therapy for the treatment of liver-based metabolic diseases including Crigler-Najjar Syndrome and Urea Cycle Disorder. The treatment is based on allogeneic adult liver stem cell technology. The major innovation of Promethera® HepaStem resides in the simplicity of the treatment - a simple injection into the vein leading to the liver – which may make it possible to avoid radical and invasive surgery such as a liver transplant. If this therapy proves to be safe and effective, as many as a hundred patients could be treated from a single liver, thus largely overcoming the organ shortage problem.
Disease: Crigler-Najjar syndrome
urea cycle disorders
Therapeutic area: Rare diseases - Genetic diseases - Metabolic diseases - Liver diseases -
Country: Belgium, France, UK, Israel, Italy
Trial
details: The trial, a prospective, open label, multicenter- phase I/II study testing Promethera® HepaStem is designed to evaluate the safety and the preliminary efficacy of Promethera® HepaStem in Urea Cycle Disorders and Crigler-Najjar Syndrome patients. Promethera Biosciences has obtained authorizations from the British, Belgian, French, Italian and Israeli regulatory authorities to initiate this study. In the clinical study, the product is assessed in a paediatric setting involving children suffering from Crigler-Najjar syndrome or urea cycle disorders.
The trial is a dose escalation study designed to evaluate the safety and the preliminary efficacy of Promethera®HepaStem. Most young patients affected by these very rare diseases have limited therapeutic options and may die at an early age. CN syndrome has an incidence of around one in a million births. It becomes apparent during the neonatal period by early intense jaundice due to unconjugated bilirubin. The UCD are a group of eight inborn errors of metabolism that affect the transfer of nitrogen into urea. Although each specific disorder results in the accumulation of different precursors, hyperammonemia and hyperglutaminemia are common biochemical hallmarks of these disorders.
Latest
news: * On November 12, 2013, Promethera Biosciences, a Belgian biotechnology company developing Promethera®HepaStem, a cell-based therapy for the treatment of liver-based metabolic diseases including Crigler-Najjar Syndrome and Urea Cycle Disorders, has announced the completion of patient enrolment for its first clinical trial. Promethera Biosciences is conducting a first-in-man trial with HepaStem in paediatric patients suffering from orphan diseases. Promethera Biosciences has successfully treated 20 patients with HepaStem in collaboration with 11 clinical centers. Given the scarcity of patients, Promethera Biosciences has conducted the trial in five countries: Belgium, France, United Kingdom, Italy and Israel. In total, 11 clinical centers actively participate in the study: Cliniques Universitaires Saint-Luc, Belgium, Universitair Ziekenhuis Antwerp, Belgium, Hopital Jeanne de Flandre in Lille, France, Centre Hospitalier Universitaire Bicetre in Paris, France, Centre Hospitalier Universitaire de Toulouse, France, Birmingham Children’s Hospital, UK, Great Ormond Street Hospital, UK, IRCCS Ospedale Pediatrico del Bambino Jesu, Italy, Meyer Children’s Hospital at Rambam Health Care Campus, Israel, Hadassah Ein-Kerem Medical Center, Israel, Schneider Children’s Medical Center of Israel. The study started in March 2012 with the first patient treated in Belgium. As of today, 20 patients aged from six weeks to 16 years have been treated with Promethera®HepaStem.
Eric Halioua, chief executive officer of Promethera Biosciences said: “ During the trial another innovation took place with the use of a mobile formulation unit operating near the medical site. This mobile production unit was used to both carry the material and to formulate the product. The GMP approval process by the Belgian authorities considered the mobile unit as an extension of the Promethera Biosciences GMP certified manufacturing unit. A sterile and closed formulation system for preparing the final product was installed in this unit, operating so that the cells could be delivered in real time at the bedside of the patient. A patent for the mobile unit has been filed and is being examined before issuance.”
The end of the trial is scheduled for October 2014 after a patient follow-up period of 12 months.
* On February 27, 2013, Promethera Biosciences has announced that it has successfully treated a patient with liver progenitor cells enrolled in its Phase I/II trial. The intervention was performed in January 2013 at the University Children’s Hospital Jeanne de Flandre in Lille (France). This patient is the first one treated in France, and the first one treated outside of Belgium where the study has been launched. This patient is a 14-year-old adolescent suffering from Ornithine Transcarbamylase Deficiency (OTCD, one of the Urea Cycle Disorders). The treatment was successfully applied over three days. The cell formulation was performed both on clinical site in Promethera’s mobile formulation unit and at the premises in Mont-Saint-Guibert (Belgium). The patient was discharged in good condition and is doing well. He is closely monitored by Dr Dobbelaere’s medical team. Administration of Promethera® HepaStem was already successfully performed in four more patients at the Cliniques Universitaires Saint-Luc in Brussels, Belgium. The safety data collected so far supports the good tolerability of Promethera® HepaStem in the phase I/II clinical study and warrants further enrollment of new patients. The clinical centers in UK and Italy are preparing to welcome the next patients for this clinical trial.
* On May 14, 2012, Promethera Biosciences has announced that it has treated its first two patients with its innovative treatment based on allogeneic adult liver stem cell technology. These patients were treated and are followed at the Cliniques Universitaires Saint-Luc (Brussels, Belgium). Since the discovery of HHALPC (Heterologous Human Adult Liver Progenitor Cells, forming the basis for Promethera® HepaStem product) by Professor Etienne Sokal and Dr Najimi at the UCL laboratories (Brussels) in 2005, Promethera Biosciences has made considerable scientific advances. The proof of concept for the therapeutic use of the cells has been demonstrated in different animal models. Between 2009 and 2011, the ‘proof of concept’ in man has been studied by treating three patients suffering respectively from Ornithine Transcarbamylase deficiency (a form of Urea Cycle Disorders), Crigler Najjar syndrome, and type 1 glucogenosis with HHALPC by Professor Etienne Sokal at Cliniques Universitaires Saint-Luc (Brussels, Belgium) within the framework of the hospital exemption rules and the approval of the Ethic Committee.
These various achievements have enabled Promethera Biosciences to obtain the first authorizations from the British (MHRA) and Belgian (AFMPS) regulatory authorities to begin the phase I/II clinical study with Promethera® HepaStem. As part of the clinical study, the product is assessed in a paediatric setting involving children suffering from Crigler-Najjar syndrome or urea cycle disorders. Most young patients have only limited alternative therapeutic options and may die at an early age.
