Is the G-BA becoming more lenient towards surrogate endpoints?

By Fisentzos Stylianou, PhD; Senior Analyst

Contact: [email protected]

“I can say on behalf of the G-BA that it is possible that we will recognise some of the surrogate endpoints that previously we did not recognise, in order to keep [CAR-T] therapies on the market,” Prof. Josef Hecken, chair of Germany’s health technology assessment (HTA) body G-BA, recently said at the German Cancer Congress (DKK) in Berlin [1].

Hecken’s statement is in response to the new statutory health insurance (SHI) financial stabilisation law that recently came into power. Under the new law, drugs rated with minor added benefit or non-quantifiable added benefit cannot be priced higher than the designated comparator, while only drugs with considerable or major added benefit may be priced higher than the most appropriate patented comparator therapy (see figure below for more details). Of note, prior to the new law, the GKV-SV and orphan drug manufacturers were free to price a drug at any price point, with the G-BA outcome being a factor influencing the results of the pricing negotiation.

The new law is significant as four of the five CAR-T therapies currently available in Germany achieved “non-quantifiable added benefit” due to several factors including, but not limited to, the use of surrogate endpoints, single arm trials, and small trial population sizes [2,3]. Novel CAR-T therapies that apply for reimbursement in Germany that cannot demonstrate considerable or greater added benefit may be priced at parity with a much cheaper therapy such as a patented antibody or chemotherapy.

CAR-T manufacturers may employ surrogate endpoints such as ORR and PFS as primary endpoints in their pivotal clinical trials as they may provide a more rapid and cost-effective approach to understanding efficacy than measuring OS data, as this may allow clinical studies to be shortened [4]. Also, unlike most conventional drugs, autologous CAR-Ts are typically administered as a single infusion and are relatively expensive due to their high production costs [5]. As a result, current CAR-T manufacturers seeking to commercialise in Germany, where the efficacy of their asset is primarily measured by a surrogate endpoint, may now be concerned about a lack of return-on-investment in this market. Patients will ultimately be affected if manufacturers are reluctant to commercialise in Germany, as they may be unable to access new life-saving and even curative therapies.

To avoid stifling innovation, Hecken stated that the G-BA is considering loosening the strict surrogate endpoint criteria for CAR-T therapies, which would allow them a greater likelihood of achieving considerable or greater added benefit. Although the G-BA has not confirmed that any changes will be made, this is significant news for CAR-T manufacturers because it demonstrates that the G-BA recognises the importance and innovativeness of these therapies. However, given that CAR-T trials, particularly for orphan indications, are also frequently criticised for their single arm trial designs and small population sizes, the G-BA may have to go further to support innovation in the advanced therapy medicinal products (ATMP) space.

We have been monitoring recent changes in the German market for the past year and will continue to do so in order to best advise our partners on how to react, plan, and adapt to the changing German market. Contact P4A to learn more about our services to support with determining ideal access pathways and follow us on LinkedIn to remain up to date on how to seize opportunities in an ever-changing space.







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