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Cell-Easy and the Toulouse University Hospital have announced that they have obtained IMPD approval for a first-in-human clinical trial. This trial will use an allogeneic treatment, developed from an autologous process, for patients with ischemic digital ulcers in systemic sclerosis. The CDMO developed the entire manufacturing process from an initially autologous one where the cell donor was the patient himself.
The innovative allogeneic approach uses cells from a single donor to produce therapeutic doses for thousands of patients. This is cost-efficient, therefore it makes the product more accessible for patients.
Cell-Easy has conceived and designed a process for the large-scale manufacturing of ASCs in compliance with the GMP (Good Manufacturing Practice) standards required by regulatory agencies. These ASCs will be used in the A-DUSE clinical trial. Prof. Gregory Pugnet, from the Internal Medicine and Clinical Immunology department, Rangueil Hospital, Toulouse, (France) is the main investigator of the trial, which is sponsored by Toulouse University Hospital.
Gaining ANSM/EMA's approval for the A-DUSE clinical trial is a demonstration of the Cell-Easy team’s ability to carry out a cell therapy development program from end to end. Some highlights from the new large-scale manufacturing process of therapeutic doses of allogeneic ASCs:
- >5,000 doses per tissue donation
- >4.109 cells per batch
- x20 cost reduction
- 26 parameters analysed per batch
The Toulouse University Hospital, through its clinical centre of investigation in biotherapy (CIC-BT) structure, stands as a pioneering cell therapy player in Europe. It has 20 years' experience in the field of cell therapy based clinical research. In a bid to kickstart the A-DUSE clinical trial safely and efficiently, Prof. G. Pugnet was looking for a robust industrial partner capable of providing high numbers of clinical grade ASC therapeutic doses. The scientific, technical and regulatory expertise of the French CDMO, and its ability to offer an end-to-end service spanning from patient sample procurement through to IMPD writing, convinced the Toulouse study centre.
“This project represents another remarkable milestone for Cell-Easy, demonstrating our ability to successfully navigate the entire life cycle of Advanced Therapy Medicinal Products (ATMP) development. Our collaborative work with physicians, supply chain partners, regulators and policymakers has enabled us to effectively address the intricacies of these therapies and establish rigorous quality standards,” said Guillaume Costecalde, president at Cell-Easy.
Beyond conventional GMP manufacturing of ASCs, the A-DUSE clinical trial required the selected partner to provide unfailing support in terms of regulatory and scientific matters, as well as medico-economic understanding of the disease. Close collaboration between Cell-Easy, CIC-BT and Prof. G. Pugnet was instrumental in achieving this objective.
In less than 20 months, Cell-Easy developed a new production process in ASC along with all the associated analytical tests for robust batch qualification.
Within the framework of this partnership, the resources made available by the CDMO have resulted in:
- Establishment of partnerships with local healthcare centres capable of selecting donors based on medical-biological criteria, of supplying human adipose tissue and of qualifying donations at GMP level, as required by EU/US regulatory agencies
- Conducting toxicity and tumorogenicity studies in mice, and
- Co-authoring the IMPD for submission to the local French agency, the ANSM
Injection of allogeneic ASC, a promising opportunity for healing digital ulcers
Systemic sclerosis is an orphan disease characterised by the development of microangiopathies and progressive fibrosis. Digital Ulcers (DUs) are common in the course of the disease and are an expression of its severity. Not only do DUs cause intense pain and hand disability, but more critically they can lead to infections that can result in gangrene and eventual amputation. With optimal standard of care only 60% of DUs are healed after three months and 46.2% experience recurrence during this period, with 11.2% having a chronic course. To date, no medication has demonstrated a positive effect on the healing of refractory DUs. In this clinical context with no therapeutic alternative, the partnership between Toulouse University Hospital, represented by Prof. G. Pugnet, the CIC-BT, and Cell-Easy, through the A-DUSE Clinical Trial (digital injection of allogeneic ASC), represents a promising opportunity for many patients in the healing of refractory ischemic DUs.
Since 2021, French players in biotherapy have been working hard to convert a promising MSC-based therapy concept into reality for patients living with ischemic digital ulcers due to systemic sclerosis.