Once an Advanced Therapy Medicinal Product (ATMP) is admitted to the European market, the next big challenge presents itself: obtaining reimbursement for the treatment. An interview about this challenge with Utrecht-based health economist Dr. Renske ten Ham.

‘ATMPs are quite expensive, so in each country the consideration must be made: do we spend our healthcare budget on this, or do we use it for other purposes?’ says Ten Ham. Her Health Economics research group at the University Medical Center Utrecht deals with the various methods and trade-offs involved, especially for products in the field of regenerative medicine. From this expertise, Ten Ham advises, among others, researchers working on ATMP development. On Tuesday, March 25, she will be one of the experts in FAST’s webinar series on challenges in ATMP innovation.

Early stage
For a developer of a new ATMP, obtaining appropriate compensation can be very complex. Ten Ham and her colleagues can help think about relevant aspects of a product at an early stage, which can prevent some problems later in development. ‘This can be done very low-key at a preclinical stage, for example, by looking at how a product compares to the market and by looking at the plausibility of developing a profitable product in an early economic evaluation. We try to make the results of this approach publicly available as much as possible, so that other developers can learn from it.’ Ten Ham is also working with FAST in this area to promote the further development of promising products.

Assessment
The final consideration of whether an ATMP will be reimbursed follows the European Medicines Agency EMA’s decision to allow the product to enter the market. ‘The procedure for EMA-approved ATMPs is no different from that for other expensive drugs,’ says Ten Ham. ‘The vast majority of drugs, about 90%, are automatically reimbursed as soon as they are on the market. Only expensive drugs are placed in lockstep and must undergo health technology assessment (HTA). And ATMPs so far almost always fall into the latter category.’ In the Netherlands, the Zorginstituut Nederland conducts the HTA and then issues an opinion to the minister. The latter ultimately decides on the inclusion of an ATMP in the basic package.
The passage through the Health Care Institute can vary, sometimes involving an extensive procedure in which patient organizations, the manufacturer and other interested parties also have the right to speak. Ten Ham: “There is an ongoing debate as to whether ATMPs should be evaluated in the same way as other drugs. After all, many ATMPs hold the promise of cure or at least long-term effect. But on the other hand, all of them involve money that you can only spend once.’
The Dutch system, in which individual insurers have a key role, further complicates this discussion. Even if in the longer term an ATMP would lead to savings, they do not always benefit the insurer that reimbursed the ATMP. After all, the patient may choose a different insurer each year. Ten Ham: “In the United Kingdom, for example, with the National Health Service reimbursing all treatments, that initial impact on the annual budget weighs less heavily.

Complex
Two issues add to the challenges surrounding reimbursement: the tension between speed and substantiation and the differences between (European) countries. Ten Ham: “ATMPs have so far mainly been developed for rare disorders with a high medical need. On the one hand, people want these drugs to become available as quickly as possible, but for careful evaluation you also need sufficient data on effect, safety and cost-effectiveness. And that is even more difficult, especially with rare disorders, because of limited numbers of patients.’
European countries are very different in their reimbursement and assessment systems. Some countries, such as Germany, reimburse drugs immediately after approval, and only conduct an assessment later. In the Netherlands, the Horizon Scan drugs and the associated lock-in apply, where an assessment is carried out first before a decision is made whether or not to proceed with reimbursement. The assessment criteria and required substantiation also differ from country to country. To change this, the Regulation on health technology assessment entered into force on Jan. 12, 2025, which should eventually lead to more harmonization. The regulation will be phased in, but ATMPs and oncology drugs are at the top of the list. Ten Ham: “The expectation is that this will eventually harmonize processes within Europe more, prevent duplication of effort and speed up access to innovative treatments. But I hear conflicting noises at conferences so far about the impact in the shorter term. Some developers and some countries say they are all ready, others still foresee a lot of problems in the concrete implementation and execution of this legislation. All in all, I think it is good first step toward more European harmonization.’

Discussion
The optimal assessment of ATMPs is certainly not the last word, according to Ten Ham. Ten Ham: “There is a lively discussion in our professional literature about how best to quantify the benefits of treatment with an ATMP. Because when you are talking about potential cure or at least a long-term major improvement, it not only has an effect on healthcare costs, but also all kinds of other beneficial consequences. A person can be part of society again, or in the case of indications for children, a huge burden on the parents falls away. If you factor all that in, you look at the costs and benefits differently. In the Netherlands, some of this is already taken into account. But for the time being the discussions about the exact methods of calculating the benefits and costs are not yet settled, and in part this is mainly a scientific discussion. The main issue here is the contradiction of paying in advance for benefits in the future. Benefits of which we are currently not always sure how long they will last. The Minister of Health has to make a decision based mainly on the information provided now. And I have to say, I’m glad I’m not in her shoes in that regard, because these are difficult choices.