After years of painstaking research, cell, gene and tissue therapies are turning in unprecedented evidence of efficacy in phase I/II. Unlike the old model, where the sole focus would now be on phase III, companies need to work simultaneously on manufacturing, logistics, pricing and getting the product to the patient, says Keith Thompson.
Advanced therapy medicinal products (ATMPs) have acquired an attribute not previously seen in drug development: velocity. “The industry has been used to a slow and linear progression through the stages of clinical development, approvals, reimbursement and commercialisation. Now advanced therapies are turning in big efficacy signals in early trials and advancing at such a rate of knots that we need a new paradigm for drug development,” says Keith Thompson, CEO of the UK Cell Therapy Catapult.
To take one example: rather than 10 – 12 years in discovery and development, Novartis expects to file for first approval of a T-cell-based immuno-oncology product in 2016, just four years after entering the field. In another case in point, Pluristem Therapeutics has agreed the design of a phase II trial of its placenta-derived PLX-PAD cells in a subgroup of patients with severe critical limb ischaemia (CLI) with the European Medicines Agency. If successful, the trial will both be sufficient for conditional approval in this indication and pave the way for submissions in ischaemic stroke, muscle wasting, hip fracture and other subgroups of CLI. Despite the clear line of sight in the clinic, much complexity remains.
New approaches are needed for manufacturing, logistics, reimbursement and delivery to the patient, if the industry is to break the mould and capitalise on shorter clinical development timelines, Mr Thompson believes. The Cell Therapy Catapult was established by Innovate UK to create a supportive environment for the commercialisation of ATMPs, and a key focus is in helping to move products out of the academic labs and small-scale GMP production facilities where most originate. The Catapult has a GMP facility under construction where companies will be able to transfer products for large-scale production and commercialisation.
There will be 12 modules each with their own handling capabilities. “The big idea is that we’ll be operating a manufacturing envelope with an overarching quality system in which a number of firms can operate – they can bring in their own people and run their own process, protecting valuable know-how” says Mr Thompson. The facility, in Stevenage, is close to Heathrow airport, allowing companies to set up pan-European supply chains for short shelf life products. “This is a critical part of changing the paradigm,” Mr Thompson says. “You need not only manufacturing but also new logistics and cold chains, both for bringing in starting material and transporting finished products.” The remarkable clinical results point to a higher therapeutic value and the potential to replace chronic disease management with a one-off treatment. This calls for a new reimbursement paradigm. “In the old model people wouldn’t be considering the health economics of products at this stage, but with the faster timelines of advanced therapies they need to,” Mr Thompson says.
The Catapult has set up a health economics and reimbursement group to provide support and assist with cost/benefit analyses. “It’s really important to be talking about this early on,” says Mr Thompson. “You don’t want to get approval and then spend two years in limbo while price negotiations drag out.” A third area where ATMPs need to remodel existing pathways is in delivering direct to the patient. This presents particular challenges in the case of autologous therapies, where cells or tissues taken from a patient must be processed and administered back to the same patient. “It’s quite unlike batch manufactured pharmaceuticals that are delivered to the pharmacy and called off by prescription,” says Mr Thompson. “There has to be a degree of integration from manufacturing to patient.” With the clear signals of efficacy coming out of clinical trials, it is time to ensure health systems are prepared and ready to adopt advanced therapies.
On 14th December, the European Biopharmaceutical Enterprises (EBE) and the European Medicines Agency (EMA) will hold their fourth annual regulatory policy summit in London. Keith Thompson is one of the speakers scheduled to speak at the event – you can hear more of his views by attending on 14th December. More information and registration here.