HTA outcome for ATMPs in the three Scandinavian countries Sweden, Norway, Denmark

What is the outcome of ATMPs that has been approved by the EMA in the Scandinavian markets?

The introduction of Advanced Therapy Medicinal Products (ATMPs) is a major challenge for HTAs in most countries. Limited long-term data, often lack of comparative clinical trial data, and high prices have forced the agencies to review their methodologies. However, what is the outcome of the ATMPs that has been approved by the EMA in the Scandinavian markets?  

One year ago, we presented a short summary of the TLV’s methodological review related to ATMPs. To date, the TLV has published two reports, with an expected third report due later this year, including a recommendation on the use of outcome-based payments. Despite the high interest and focus, there are still only a limited number of products that have been approved and that have been recommended to be used locally.  

From 2018 until May 2023, 15 products have been approved by the European Commission.* However, in 2022, Zynteglo® had its marketing authorization withdrawn at the request of the manufacturer. Of the remaining 14 products, six products are still in the process of evaluation by the HTA agencies in the three countries or that the manufacturers have not yet submitted the relevant documents. In addition, the HTA evaluation of the CAR-T product, Breyanzi® has been postponed due to production limitations.  

Of the remaining seven ATMP products, five have been recommended to be used by the Swedish NT Council after an evaluation by the TLV. For these products, the manufacturers have agreed to provide them with a confidential discount. Some products have additional indications but most of those added indications are still under evaluation. In Norway, six products have been approved by the Decision Forum after an evaluation by NoMA, and a price negotiation with the Norwegian procurement organization, LIS. In Denmark, there is information on four HTA-approved ATMP products, with three products with a discount agreement.

There are some differences in terms of HTA outcome in the three markets. For example, Tecartus® is recommended to be used in Sweden but has not been evaluated in Norway, while there is no information about an HTA in Denmark. The outcome for the stem cell therapy product, Alofisel® also differs between the three markets, i.e., it is not recommended to be used in Sweden and Denmark while it is recommended in Norway. Yescarta® is recommended to be used for the diffuse large B-cell lymphoma (DLBCL) indication and primary B-Cell lymphoma (PMBCL) in third line in Sweden and Norway, while it is not yet approved in Denmark. It is also interesting to note that the Danish Medicine Council decided that the gene therapy product, Libmeldy®, should not be evaluated as the treatment will be provided outside of Denmark (although the Danish welfare system must pay for the treatment).  

The timeline between marketing authorization and local HTA recommendation varies between products and countries. The shortest timeline is for Kymriah®, four months in Norway, five in Denmark, and nine in Sweden. The longest is for Luxturna®, 31 months in Sweden and Norway while it took only 10 months in Denmark. Another product with huge differences in timeline is Yescarta, for the DLBCL indication.  It took 46 months in Norway (after two previous rejections) while it took 13 months in Sweden. In Denmark, the product was not recommended to be used by the Danish Medicine Council in 2019 but they are currently reviewing it again. 

Three ATMP products, Libmeldy, Tecartus and Zynteglo have been evaluated by the joint Finnish, Swedish and Norwegian HTA collaboration, FINOSE. Recently, there was a price negotiation between the Nordic joint organization, Nordiskt Läkemedelsforum (Nordic Drug Forum) and Orchard Therapeutics, the manufacturer of Libmeldy.   

In summary, it is likely that the HTA methodology will change because of the introduction of ATMPs. This may also include pilot tests with different payment methods and in particular, there is an interest in Sweden towards outcome-based payments. Finally, the use of the joint evaluation through FINOSE and the use of the Nordic Drug Forum as a negotiation platform, may lead to a harmonization in decisions and timelines. This harmonization may be further strengthened by the introduction of the Joint Clinical Assessment process within the EU countries.   

* Before 2018, nine products have been approved, of which five have been withdrawn 

Sources are available upon request