What do you think of gene therapy

"The knowledge about gene therapy is so far very little"

TK: Which gene therapy drugs are already on the market and what can be expected in the near future?

Tim Steimle: There are currently five gene therapeutics on the market in Germany. Three of them are used for different cancers. The other two are used for some form of early childhood blindness or for a hereditary fatal immune deficiency.

Gene therapy for the treatment of spinal muscular atrophy, a serious neurological disease, has been approved in the USA since May. If left untreated, this leads to the death of the affected children in the first few years of life. Approval is also expected for Europe in the coming months. This also applies to gene therapy for the treatment of beta-thalassemia, a disease in which the correct formation of red blood cells is impaired.

Approval for gene therapy against haemophilia, the so-called hemophilia, is expected in 2023. A total of around 50 gene therapies against various diseases are currently in clinical testing.

TK: Which improvements for patients are associated with this?

Steimle: The therapies are often the only or the last treatment option for patients. For example, gene therapies are used in cancer patients who can no longer be treated with the therapies available up to now. Some of these patients can thus be given more life.

If one looks at gene therapy for the treatment of spinal muscular atrophy, which is about to be approved, experts assume that this therapy even has the potential to cure a previously fatal disease.

Overall, these therapies are associated with very high hopes. However, the approval studies were only carried out on very few patients, which is why the knowledge about these preparations with regard to their effectiveness, but also possible risks and side effects, is so far very low. For this reason, no one can say at the moment whether the therapies will deliver what they currently promise in the long term.

TK: TK has developed the "dynamic evidence price model" as a suggestion to make expensive drugs affordable. How does this model work?

Steimle: The dynamic evidence price is a model for sustainable financing of novel (drug) therapies. We see that the AMNOG system, which is good in itself, is only suitable to a limited extent for these new therapies. Why is that? In contrast to "classic" drugs, gene therapies are often given only once. The total therapy costs are therefore no longer spread over a longer period of time, but are incurred in full at certain points. This completely shifts the financial risk to the cost bearer.

This is particularly noteworthy, since accelerated approval procedures are often the basis and the data basis on the therapeutic value is therefore limited. We also observe that the therapies do not find their way onto the market by themselves. This is due to the special demands on the treating physicians, the high costs and the often necessary inpatient administration of the therapies.

We are now faced with the great challenge that on the one hand we expect groundbreaking therapeutic innovations that should be available to our policyholders quickly, but on the other hand we want to guarantee a high quality of care and agree on reasonable prices based on the actual benefit. The model of the dynamic evidence price serves as a bridge between the economic interests of the research industry, the needs of patients for fast and evidence-based care and all of us striving for system stability.

The model stipulates that the G-BA decides six months before approval whether the price for a drug is determined according to the AMNOG procedure or according to the dynamic evidence price model.

The basis of the dynamic evidence price is the systematic generation of phase IV "real world" data in order to close evidence gaps. For this purpose, patients who are being treated with the corresponding drug are compulsorily entered in the register. It is imperative that these registers are managed by an independent body to ensure neutrality. In this way, the evidence gaps that existed when entering the market can be closed successively, which contributes to the greatest possible patient safety.

The first phase of data collection lasts 24 months. The first reimbursement amount negotiation then takes place on the basis of this data. This process is repeated every twelve months. This means that the reimbursement amount is renegotiated every twelve months based on the most current database, i.e. dynamically adjusted.

This adjustment can be made upwards with positive data for long-term effectiveness and safety, but also downwards with negative data. In this way, the price of the drug corresponds to its therapeutic value at all times and the risk for the cost bearers is minimized. Not only does the insured community benefit from fair prices at this point, but also the pharmaceutical industry. Because highly effective preparations are rewarded more than less effective preparations.

The price of the drug in the first 24 months can be freely selected by the pharmaceutical company up to an upper limit defined by EU prices. If the manufacturer wants to use the data collected in the registers, he has to accept a discount on his price. In order to promote the research and development of pharmaceuticals in Germany and Europe, it should be possible for entrepreneurs who research and develop in Germany and Europe to add a premium to their price.

TK: Will manufacturers accept a cap in the first 24 months?

Steimle: The regulation of an upper price limit for pharmaceuticals has been used in many other European countries for years. A similar concept already exists in Germany for vaccine supply. Therefore, we do not see any acceptance problems with the manufacturers, especially since they will have an interest in placing their product on the German market. The feedback from the pharmaceutical industry on our model has so far been very positive.

TK: Are there enough patients for registry studies?

The number of patients treated with gene therapies has so far been very low. This is not going to change anytime soon in the next few years. Therefore, our model provides for mandatory entry in the register. Because every patient contributes to generating a little more evidence. In these therapeutic areas, however, we will never reach the numbers of classic approval studies, which is why it is all the more important to collect all possible information. It would be desirable to set up Europe-wide registers so that knowledge can be bundled and information on long-term effectiveness and safety can be generated more quickly.