The Joint Clinical Assessment (JCA) is now mandatory for all new advanced therapy medicinal products (ATMPs). This has huge implications for sponsors, given the unique nature of ATMPs. Navigating the JCA process will therefore require sponsors to think much more carefully about the potential clinical obstacles their product may face in the health technology assessment (HTA) process.
The clinical pathway that sits around ATMPs is complex – in no small part due to the fact that these products largely treat rare diseases. Clinical management of ATMPs is very different from any other treatment. These therapies require specialist handling, special equipment, a multifaceted supply chain network, and expert oversight and monitoring – all of which are extremely costly to the healthcare system.
The cost of long-term monitoring
Unlike more common drugs, such as blood pressure medication, monitoring does not involve a simple blood test to check liver and kidney numbers. Rather, the tests required for ATMPs are specialised or require specialist knowledge. Tests might include organ-specific toxicity testing to assess the drug’s impact on the patient’s liver or kidney.
ATMPs for rare diseases may require specific assays for diagnosis and dedicated devices to monitor a patient long term. These require heavy investment and will involve significant cost for the healthcare system.
By having the JCA carried out in parallel with the EMA’s marketing authorisation assessment, sponsors increasingly must consider potential cost obstacles to their innovations. Questions they should be asking are: Should they be bringing their drug to market in parallel with an in vitro diagnostic company? Are there other ways they can help to drive down the cost of administration?
We know that the EMA’s Committee for Medicinal Products for Human Use will be sharing information with the JCA committee, and vice versa. Have you thought about how your product will be used in the market? Have you gathered relevant real-world evidence to back up your claims?
Be prepared with clinical data and RWE
With so much more attention being paid to affordability for the healthcare system and providing data to demonstrate the value a therapy brings, it is becoming imperative that ATMP innovators prepare and provide clinical data and RWE to back up claims for both regulatory and downstream HTA/reimbursement purposes. And that data needs to include potential longer-term risks and how those will be managed and monitored. After all, the HTA bodies will be looking for affordability, long-term monitoring and evidence of the therapy’s value.
If the patient needs to have a full-body MRI, that cost needs to be analysed and presented as part of the JCA submission.
For example, cardiovascular toxicity has been found to be a long-term safety concern with many cell and gene therapy platforms, with about 10% of patients that have received CAR-T therapy potentially developing new heart problems. Heart surveillance, therefore, needs to be applied to any of these therapies, including electrocardiograms, echocardiography, and biomarker assessments. Ongoing imaging, including regular MRIs, will be required.
Thinking longer-term for a successful outcome
Start thinking about the other elements involved in not only delivering the product to the patient, but managing and monitoring them – especially given that many, if not most, of these products target patients with rare or ultra-rare diseases. Who are the clinical specialists that will need to be involved in monitoring? What types of monitoring technologies will be required? And how can those costs be better managed by the healthcare system?
ATMPs can be life-saving and life-changing, but their success requires acceptance by both the regulators and the HTA bodies.
To ensure they are ready for the JCA, developers should engage early with the regulators and HTA bodies, plan evidence generation beyond clinical trials, and anticipate real-world monitoring needs that will be required by all authorities.
The clinical pathway that sits around ATMPs is complex. It involves not only highly complex and as such costly administration … but also highly specialised monitoring.