Periodic Reporting for period 1 - BALXPAND (The HepaRG-Bio-Artificial Liver: Feasibility of commercialization and expansion of business plan)
Período documentado: 2017-03-01 hasta 2017-08-31
Due to a shortage of donor livers, more than 30,000 patients are on the liver transplant waiting list in Europe and the US. Strikingly, each year, there are only about 12,000 donor livers available in these regions and the average waiting time of patients on the waiting list is 115 days in Europe and 232 days in the US. A significant share of the patients die while being placed on the waiting list. An even larger share of patients suffers from the effects of late transplantation because, while waiting before reaching the criteria for liver transplantation and subsequent availability of a donor liver, their condition worsens and morbidity and mortality after transplantation will increase. There is no treatment available to reverse the disease progress substantially and prevent transplantation.
The SME Hep-Art has, together with academic partners, developed a BAL, named HepaRG-AMC-BAL, which is a bioreactor embedded with HepaRG cells, from a human liver stem cell line, that mature to high level inside the BAL. This HepaRG-AMC-BAL is developed to treat the plasma of the end-stage liver disease patients (Fig. 1) and temporarily replace liver function to bridge the period towards transplantation, or to support liver restoration until transplantation will become superfluous. A preclinical test showed that the HepaRG-AMC-BAL-prototype treatment provided effective liver support during liver failure.
The overall objective of the BAL2B project was to prepare the HepaRG-AMC-BAL for a clinical trial to eventually test the safety and efficacy of this treatment modality. To that means Hep-Art aimed to improve the production of cells for the HepaRG-AMC-BAL, obtain insight into the production costs of the HepaRG-AMC-BAL in the clinical implementation phase, to map suitable Contract Manufacturing Organisations (CMOs) with cleanroom production facilities for producing quality-tested HepaRG-AMC-BALs, and to develop a feasibility plan with the results of the study.
The main results:
• Data from 6 runs with the automated culture system: the system was easy to operate and cells harvested from the system were comparable in their functionality as cells harvested from parallel culture flasks, however the system was not cost-effective, as the expansion of the cells was limited;
• A first pilot experiment showing that considerable simplification of the logistics is within reach;
• Development of a strategy for the most cost-effective and simple process from cell to BAL at bedside with an indication of the costs, and with the requirement of only one CMO per continent, showing feasibility of the business;
• Identification of a suitable CMO for Europe to start with, which is willing and capable to quality-controlled production of the cells and BAL cultures and the transport to the clinic;
• Identification of a suitable large medical device company for partnering with Hep-Art;
• A feasibility report implementing the findings of the BALXPAND project.
This opens new perspectives for end-stage liver disease patients by bridging them to liver transplantation with less morbidity or even by stimulating restoration, making liver transplantation superfluous. This may also reduce the health care burden for society, saving the high costs for liver transplantation. For Hep-Art it is a break-through, as it brings a small clinical trial within reach, which is essential to make Hep-Art attractive for partnering with a large medical company, which is needed for a follow-up clinical trial with a large number of patients to show efficacy of the BAL treatment.
The actions to be undertaken up to the first (small) clinical trial:
• Scale up the expansion of cells for the simplified logistical process;
• Scale up the transport process of the BAL cultures;
• Make the whole production and transport process quality-controlled by the CMO;
• Prepare and conduct a clinical trial in 5-10 end-stage liver disease patients to show safety and feasibility of the BAL treatment;
• Refine the business plan to inform and attract a suitable partner;
• Obtain financing for these activities.