#apaperaday: How to pay for individualized genetic medicines

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: How to pay for individualized genetic medicines

Paper a day with a comment in Nature Medicine about paying for individualized genetic therapies by Pian et al. DOI: 10.1038/s41591-024-03071-x.

With new developments as gene therapy, antisense oligonucleotide (ASOs) & gene editing come opportunities to treat individual patients with rare genetic diseases or variants. Tim Yu & stopbatten showed feasibility to develop individualized ASO for a patient with Batten (milasen).

The development of these approaches is expensive, but authors argue here for ways to make this affordable. First initiatives have been/are funded by institutions and philanthropy. However, it will be challenging to scale this from one or a few cases to thousands or millions.

Authors outline how we can learn from the organ transplantation field for this scale-up. This also started with very few pioneering cases but then increased exponentially due to data sharing and local efforts. Also here the first cases were much more expensive than future cases.

Or in other words, by learning from each case, future developments can be more streamlined & thus less expensive. Especially ASOs are relatively cheap with regards to cost of goods ($40k is likely enough for a lifelong supply for local treatment in brain and eye diseases).

Notably, there are additional costs involved for the development and maintenance. Again, only data sharing and experience sharing can make development cheaper beyond the local sites doing the development. Transparency is key here.

Authors also outline that the academics leading the N=1/few therapy development can take an ethical stand when needed, like the organ transplantation experts did when people started to offer organs for profit. And they can develop tools, like those matching organ to donor.

From a regulatory perspective, authors focus on USA jurisdiction, where FDA has issued guidelines for N=1 ASO development in 2021 & also on reducing the need for animals act in 2023. The hope is that developing ASOs in a platform type of approach will reduce administrative burden.

A personal sidestep about platforms: this is not a blanket approval for all ASOs, but an approach to allow certain shortcuts or reduced testing when there is sufficient similarity between tools. For ASOs specifically, chemical modification, route of administration, etc.

Note that one can only build on existing data when such an ASO has been approved for a larger group of individuals (e.g., nusinersen or tofersen). If you have a new chemistry for N=1, you will not know whether tolerability or lack of it is due to the chemistry or the disease.

How to fund this? Authors outline that ideally payers reimburse. The costing model will be challenging, with development and care costs reimbursed with a small margin to incentivize future developments. Also here transparency will be key.

Other models could be a subscription model where expert treatment centers subscribe to individualized treatments with a specific fee and then beyond the first patient treatment involves no additional cost. However, this may be challenging for access:

e.g., you may have to travel far to get access to an institute that has subscribed to the treatment. In a small country like the Netherlands this may not be that big of an issue, but for larger countries it might. I do agree with limiting treatments to expert centers.

I commend the authors for speculating about costing models. This is a difficult discussion we also face with the DCRT (Dutch Center for RNA Therapeutics). The challenge also is that we do not really know what development will cost once it is more streamlined.

This makes discussions with payors hypothetical. What was not discussed in this comment (probably due to length constraints) is WHEN treatments should be reimbursed. i.e., how to measure efficacy. This is worthy of a commentary of itself as this also needs to be individualized.

What we have heard from discussions with many stakeholders is that outcome measures should be patient-relevant and reflect not only biomarkers (though treatment-responsive biomarkers are VERY useful) but also the impact on the patient (quality of life/disease burden).