Creating characterisation and potency assays for an autologous cell therapy product

Rexgenero are a leading regenerative medicine company developing advanced cell-based therapeutics for the treatment of serious diseases such as critical limb ischemia.

The challenge

Critical limb ischemia (CLI), the end stage of peripheral arterial disease, is a severe obstruction of peripheral arteries, markedly reducing blood flow to the limbs. This often results in severe pain, skin ulcers, and gangrene leading to the requirement of limb amputation. Mortality rates can be as high as 40% within a year of diagnosis.

The only effective treatment for CLI is manual revascularization using surgical bypass or endovascular methods. However, a significant proportion of patients are not suitable for revascularization due to multiple conditions that lead to cardiovascular complications. As a result, limb amputation is often the only remaining treatment option.

Creating characterisation and potency assays for an autologous cell therapy product

Rexmyelocel-T, an autologous cell therapy product currently under development by Rexgenero, is entering Phase III clinical trial for the treatment of CLI. Rexmyelocel-T uses bone-marrow derived mononuclear cells which, following transfusion into CLI patients, migrate to the ischemic tissue and induce new blood vessel formation.

During the manufacturing process, product quality must be robustly measured. The complex mechanism of action of Rexmyelocel-T, makes the development of tests that measure key functional parameters such as potency, difficult.

The solution

The team at Cell and Gene Therapy Catapult (CGT Catapult), in collaboration with Rexgenero, applied a series of specially designed analytical development tools to define the current characterisation and potency assays used during the production of Rexmyelocel-T, and determine their suitability. The team looked at assay performance and robustness, sources of variability and potential modes of assay failure. By observing the assays being performed during Rexmyelocel-T production at the Rexgenero laboratory in Spain, and working closely with their scientists, an optimisation plan was produced and delivered to ensure the assays could support ongoing clinical development.

Creating characterisation and potency assays for an autologous cell therapy product
CGT Catapults analytical development labs are located in Guy's hospital, London

This collaboration allowed Rexgenero to tap into the resources of the analytical development team at CGT Catapult and the state-of-the-art analytical development lab in Guy’s hospital. They were also able to meet tight deadlines leading up to the commencement of their Phase III clinical trial.

The CGT Catapult team will now continue to support Rexgenero in developing and validating a new rapid surrogate potency assay to support production of Rexmyelocel-T to ensure the product is both safe, effective and viable before being delivered to the patient.