After huge investment in the basic science and translation to the clinic, Europe’s advanced therapies companies are accumulating data, which indicate these products have an unprecedented effect. Now effort is needed to develop manufacturing, organise logistics, agree reimbursement and ensure patients get the benefits. Vital Transformation reports for EBE from the ARM Conference.

As one pioneering company after another took the stage to report progress at the Alliance for Regenerative Medicine (ARM) Investor Day in London earlier this month realisation dawned: cell, gene and tissue therapies, are poised to deliver long-promised clinical benefits. The level of benefit is such that some products are being submitted to the European Medicines Agency (EMA) on the basis of phase II data.

One example is Cell Therapy Ltd’s Heartcel, an allogeneic stem cell therapy for treating severe heart failure. Although the phase II study of Heartcel involved only 11 patients, all remain alive an average of 28.4 months after receiving the cells as an adjunctive treatment to coronary artery bypass graft. This compares to an expected mortality rate of 70 percent per annum. Furthermore, none of the 11 has experienced any further cardiac events.

Another case in point is Pluristem Therapeutics’ PLX-PAD placenta-derived product which, following acceptance into the EMA’s Adaptive Pathways pilot, is poised to enter a phase II in patients with severe critical limb ischaemia (CLI). If positive, this will lead on to conditional approval. Approval in this subgroup of CLI patients will support future submissions in other areas of high unmet medical need, including ischaemic stroke, muscle wasting, hip fracture and additional subgroups of CLI.

Another example of significant clinical benefit comes from TiGenix’s Cx601 in the treatment of complex perianal fistulas caused by Crohn’s disease. All 103 patients receiving Cx601 in the placebo-controlled phase III study that reported in August had failed on previous therapies. In the trial almost half of patients receiving Cx601 were in remission, with all lesions healed, six months post-treatment. TiGenix plans to submit the product to the EMA for approval early next year.

But as discussions at the ARM Investor Day highlighted, positive clinical data is not the end of the story. The sector must focus on other issues including manufacturing, supply chains, reimbursement and delivering to patients, if advanced therapies are to be adopted at scale and become commercially successful.

If clinical development is now relatively de-risked, scaling up manufacturing and implementing new supply chains for sourcing the cells and tissues that go into these products, remains highly complex.

The cost of goods is a critical factor in making a commercial success of advanced therapies. Most products began their lives in academic labs with small-scale GMP facilities, attached to a teaching hospital. It is necessary to scale up production capacity and geographical reach, whilst also reducing the cost of the finished product.

In addition, Europe’s advanced therapies pioneers must work out how these products will fit into modern healthcare systems and reach agreement with payers and commissioning bodies.

The European Commission’s Expert Group on Safe and Timely Access to Medicines for Patients (STAMP), set up earlier this year, has highlighted that patient access to advanced therapies depends not only on optimising regulatory oversight, through mechanisms such as the Adaptive Pathways pilot, but is also linked to health technology assessment (HTA) and pricing and reimbursement.

As the ARM conference heard, there remains significant work to be done in modelling the health economic benefits of advanced therapies. Recognising that reimbursement stands between approval and access, the Adaptive Pathways pilot involves HTA and reimbursement bodies in discussions about endpoints of relevance to them.

This is complicated because HTA and reimbursement are in the hands of member states. But as one example of how this might play out in practice, Pluristem expects that reducing length of hospital stays will be a secondary endpoint in the pivotal phase II trial of PLX-PAD in severe CLI.

These are early days in the process of persuading payers that rather than providing a lifetime of chronic care, they should accommodate large, one-off, upfront payments.

But as the ARM conference heard, advanced therapies are now backed by safety and efficacy data that indicate they will address unmet medical need. This will justify a new reimbursement paradigm, which recognises their therapeutic value and potential to reduce healthcare costs.

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