Outlook for advanced therapy medicinal product price negotiations in Germany

Price negotiations as part of the AMNOG benefit assessment 

The maximum reimbursable price is negotiated according to §130b SGB V, based on the results of the preceding benefit assessment. Within 4 weeks after the resolution of the benefit assessment is published, the price negotiations between the pharmaceutical company and the National Association of Statutory Health Insurance Funds begin, lasting over a period of 6 months. Factors considered during the negotiation are the result of the Federal Joint Committee (G-BA) assessment, the annual costs of comparable therapies, the price of the drug in specific countries, and the anticipated sales volume. 

Generally, if the G-BA, as a result of the assessment, comes to the conclusion that no additional benefit was proven by the provided evidence, the reimbursed price will not be higher than the annual therapy costs of the comparative therapy that were set by the G-BA during the process. Another possible outcome could be that the drug will be subject to reference pricing, if fitting reference group exists. Furthermore, if the G-BA has defined a selection of multiple drugs as appropriate comparators, the reimbursed price will be linked to the most cost-efficient alternative. If the manufacturer, however, was able to demonstrate an additional benefit with the presented evidence, the price negotiations will focus on the extent of the price premium over the selected comparators.  

For orphan drugs, the additional benefit is already set by law and the G-BA only decides on the extent or magnitude of the additional benefit. No comparative therapy is set by the G-BA, so other factors like the therapeutic field and result of the G-BA assessment weigh more in the price negotiation. However, if after launch, the moving annual total in sales of the assessed drug exceeds 50 Mio Euro, the pharmaceutical company has to submit a new dossier, with comparative clinical data, also prompting a new price negotiation. 

In the case that no mutual consent can be accomplished in the negotiations within the time frame of 6 months, an arbitration board ultimately will decide on the final price. The time frame for the decision of the arbitration board is around 3 months; however, the final price is valid retroactively 12 months after market launch. It has to be noted that the initial price at market launch can be set freely by the manufacturer, and health insurances will have to pay that price, if the patient is being treated within label. 

Table 1 presents the price in the first year after launch and the negotiated price of gene and somatic cell therapeutics in Germany. To date, prices for all Advanced Therapy Medicinal Products (ATMPs) were reduced after the negotiations; none have needed to undergo the arbitration board procedure. 

Table 1. Overview of prices for gene and somatic cell therapeutics in Germany 

Aside from the negotiation according to §130b SGB V, further negotiations by individual or groups of health insurances are permitted by law (§130a SGB V and §130c SGB V). These agreements (§130a-c SGB V) do not necessarily entail simple rebate contracts as they also can be linked to value-based considerations. Depending on the market situation, these voluntary agreements can be negotiated before and/or after the mandatory price negotiation.

If the G-BA cannot sufficiently assess the benefit for a drug because of small trial populations, or accelerated authorization and therefore lack of clinical evidence, the result of the benefit assessment can be terminated. In these cases, the G-BA can request the collection of additional post-authorization data by the pharmaceutical company. The framework of the real-world data collection has to be decided on in collaboration with the G-BA, potentially creating additional challenges for the manufacturers. 

Novartis entered into an agreement for Kymriah^® with various statutory health insurances via the GWQ Service Plus GmbH in March 2019, before the final G-BA assessment was announced. This contract is outcome-based: if the patient dies within a specified period of time, Novartis is required to partly pay back the costs for Kymriah^® due to the limited therapeutic success. Similarly, German health insurances and Gilead signed an outcome-based discount agreement for Yescarta^®. For Zolgensma^®, the contract considers several (not specified) patient-relevant outcomes; if these outcomes are not met, the pharmaceutical company has to pay back up to 100% of the drug costs.

The contracts for these reimbursement models, as well as associated negotiations, are strictly confidential and further details are not known. Nevertheless, these contracts represent a reimbursement model for existing and future high-priced medicinal products.

Further reimbursement possibilities

As mentioned, the first year after launch is a year of free pricing in Germany after which the launch price is replaced by the negotiated price (§130b SGB V). This period may lead to some uncertainty until the maximum reimbursable price is set.

If healthcare professionals have concerns on whether a highly priced innovation will be reimbursed, they can always ask health insurances for a check or approval of cost coverage in single cases (§13 SGB V). However, this process takes on average at least 4 weeks until approval. In some cases (as mentioned previously), special care contracts are negotiated to set incentives.

Most of the ATMPs are only available for inpatient treatment. For inpatient use, it is possible to apply for an extra budgetary reimbursement—the Neue Untersuchungs- und Behandlungsmethode (NUB). This pathway is relevant, if the new drug is not sufficiently reimbursed or covered by an existing German diagnosis-related group (G-DRG). The hospitals can apply for an NUB every year for the subsequent year from September 1st to October 31st to the Institut für das Entgeltsystem im Krankenhaus (InEK). Applications need to be repeated year by year until the cost for the new drug is implemented in the G-DRG system (at least for 2 years). Following the submission, every NUB application will be assigned a status, determining if a reimbursement negotiation is permitted:

• Status 1: The innovation meets all InEK criteria for an NUB (new, innovative; low number of patients, leading to a large cost variance in the existing DRG; higher average resource use as already covered by the DRG) and is therefore fully accepted by the InEK. Hospitals now have the possibility to negotiate a separate budget for the new technology.
• Status 2: The criteria mentioned above were not met leading to a rejection of the positive status. Hospitals do not have the option to negotiate a separate budget for the new technology.
• Status 3: Submission of the NUB application after the due date (Oct 31). Hospitals may negotiate a separate budget even without the InEK decision. This status is not relevant in practice.
• Status 4: The InEK rates the submitted information as implausible and/or not verifiable, or the innovation is not available at the time of the final decision. In exceptional cases, hospitals may also negotiate an NUB add-on payment on an individual basis. 

If the NUB status is 1, 3, or 4, the hospital can negotiate (add-on) reimbursement with the health insurances. Table 2 reflects the way innovative inpatient treatments have been incorporated into the DRG system over the past 5 years. 

Table 2. Overview of NUB atatus according to InEK assessment  

For the chimeric antigen receptor T-cell (CAR-T) therapies Kymriah and Yescarta, the first NUB was Status 2, followed by 4 and now 1, which perfectly reflects the route to market for a highly specialized inpatient-use medicine. As a new, innovative inpatient treatment, the application also includes necessary treatment components or steps, such as apheresis for material preparation. These services are additional effort for the hospital and are only related to the new treatment. For these services, hospitals might face a reimbursement gap as usually no reimbursement code exists with inpatient reimbursement being very limited. As such, discussions started on how to sufficiently finance these additional efforts for the application of CAR-T—and probably for other gene and cell therapies. 

Outlook for pricing of ATMPs in Germany

The challenges for a successful way to the market for ATMPs are mainly two: the assessment of evidence by the regulator and the affordability to payers. Manufacturers should prepare for the G-BA to implement mandatory disease registries in cases of non-conclusive evidence at the time of market launch. The G-BA will be part of setting up the methods and requirements for these individual registries, and this will likely become the standard for ATMPs. ATMP price will be significantly reduced over time if a company is non-compliant in setting up a real-world registry. From the payer perspective, the use of real-world evidence data is anticipated to rise significantly. Pay-for-performance agreements linked to clinical outcomes of a drug will rise, but discounts and other specifics of the contract will most likely remain confidential.

The article should be referenced as follows: 

Kuchenbecker U, Konstankski M, Thamm K. Outlook for advanced therapy medicinal product price negotiations in Germany. HTA Quarterly. Spring 2021. https://www.xcenda.com/insights/htaq-spring-2021-outlook-atmp-germany

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