The G-BA implements post launch real world evidence generation for Zolgensma® 


Nasos Kipentzoglou, Analyst and Eleanor Butler, Consultant at Lightning Health review the recent approach that the G-BA has taken in requiring the mandatory collection of real world evidence for Zolgensma.

The law for more safety in the supply of pharmaceuticals (GSAV) was passed by the German parliament in June 2019. This enables the G-BA to ask for additional real-world evidence (RWE) following the initial assessment for products with conditional approval (given due to missing evidence) and orphan drugs (where evidence is considered low). 

For any post-launch registry data requested, the G-BA is obliged to check this regularly (at least every 18 months)and if newly collected data does not allow for the quantification of an additional benefit, this can result in a revision of the original benefit level and the reimbursement price. Furthermore, the GKV-SpV (National Association of Statutory Health Insurance Funds) can request a re-evaluation of the reimbursement price where the G-BA is aware that no registries have been set up, will not be set up or due to other reasons cannot be set up. Using this approach, the G-BA aims to close existing knowledge gaps and improve the evidence base for benefit assessments. 

Following conditional EMA marketing authorisation in May 2020, patients in Germany were the first in Europe to receive Zolgensma at the start of July, costing €1,945,000 under free pricing arrangements prior to the G-BA benefit assessmentAt this price, Zolgensma is considered to be the world’s most expensive drug and in order to gain access in Germany, Novartis negotiated innovative pay for performance contracts at the sickness fund level.  

Orphan drugs in Germany benefit from an automatic added benefit from the G-BA, without the need for a comparative assessment against an appropriate comparator therapy (ACT). However, if the value of sales at the GKV-SpV expense exceed €50 million per year, an ACT must be defined, and a full benefit assessment undertaken. During the first 6-months of sales in Germany, Zolgensma exceeded this threshold. 

On 4th February 2021, the G-BA announced the plan for the first mandatory collection of RWE for an orphan drug undergoing the AMNOG assessment process. Novartis will have the obligation to collect RWE for Zolgensma, in a new comparative registry study related to spinal muscular atrophy (SMA). Novartis plans to use the prospective RESTORE registry which will enrol patients from the US and Europe in order to monitor the treatment of SMA. Nearly 500 children with SMA will be included in the study comparing Zolgensma and Spinraza (defined as the ACT), with a follow-up of 15-years. Data will inform a new assessment to be completed by 2027 (the provisional benefit assessment is due for publication by the end of Q3 2021). 

Manufacturers have expressed their concerns over the additional economic burden associated with RWE generation under the GSAV law (assumed to be on average €1.1 million), the price reductions that might be imposed if companies fail to collect the data and the fear that registries will be used as a cost-containment tool. 

As Zolgensma represents the first product to go through the new process for the mandatory collection of RWE in Germany, this will be an important case study regarding the process for post-launch evidence generation in Germany, and the implications for the benefit assessment and pricing agreements. Furthermore, given the ongoing requirement for payers across healthcare systems to balance the need for rapid access to innovative disease modifying therapies, with potential uncertainties within the clinical and economic evidence available at launch, the successful implementation of this approach in Germany could have wider future implications across European healthcare systems.  

Lightning Health has extensive experience in supporting the evidence generation, pricing, market access strategy development for new advanced therapies. For more information on the Lightning API payer and physician insight platform and strategic consulting services please get in touch with a member from our team, at 




Article published 18 February 2021.