• Melanie Senior

Germany mandates real-world data collection for gene therapy Zolgensma

Updated: Mar 31

Germany’s HTA body is telling Novartis exactly what post-approval efficacy data it needs to see for SMA therapy Zolgensma. As gene therapies multiply, more such mandates may follow.

Post by Melanie Senior, MA/MSc, Senior Consultant, RJW&partners

This year marks the tenth anniversary of Germany’s AMNOG law, which introduced the country’s now-familiar added-benefit assessment process. As if to mark the occasion, the G-BA has for the first time mandated that a drug manufacturer (in this case, Novartis) collect real-world evidence on how well its gene therapy Zolgensma actually works in practice. And not just any evidence: G-BA has set out precisely what data must be collected, how, and for how long.

Evidence-collection was already on the cards for Zolgensma: the European Medicines Agency granted the drug conditional approval in 2020 for use in infants suffering from spinal muscular atrophy, a rare but often fatal genetic disease that leads to muscle wasting and loss of movement. Conditional approvals enable patients to access important new medicines early, with less data than would normally be required. The idea is that further efficacy and safety data are collected post-approval, including via registries.

In practice, that doesn’t always happen – certainly, conclusive data can take a while to emerge. Hence Germany’s decision to take things into its own hands. Due to the “limited informative value” of the clinical data available so far, the G-BA has told Novartis to carry out a registry study “in order to close the evidence gaps.” Critically – and unsurprisingly – the G-BA wants a direct comparison of Zolgensma with Biogen’s existing SMA treatment Spinraza, looking at deaths, illness course and complications. With help from IQWiG and other medical experts, G-BA has specified the exact study protocol. Any doctors who want to use Zolgensma must participate in data collection. G-BA has even set out how Novartis should evaluate the data as it emerges.


In a sense, G-BA is getting ahead of the game: rather than assessing the drug later this year and coming up with a list of evidence gaps (and, likely, inconclusive added benefit), it hopes to be in a position to properly assess the therapy by summer 2027 at the latest.


Manufacturers should take note of this decision, for two key reasons.

The first is that the announcement reveals G-BA’s increasing frustration at the lack of (what it sees as) robust evidence of many new drugs’ benefit. “We are getting medicines approved earlier and earlier with increasingly weaker evidence,” declares the release.


Any company seeking decent reimbursement in Europe’s largest market must ensure that appropriate data is provided. G-BA’s approach may not be universally liked, but the agency is consistent in what it asks for. Seeking advice – including from G-BA itself – is recommended.


The second reason is that as orphan drugs (including gene therapies) multiply, such evidence-requirements are likely to become more common. G-BA says this new approach “will only apply to a few active ingredients.” But that remains to be seen. The US registers over 4000 gene therapy trials (completed or ongoing); many resulting drugs are designed as one-time treatments, with price-tags to match (Zolgensma costs over $2 million in the US). Industry experts draw parallels between this new modality and the arrival of biologics three decades ago.

Greater competition will add further pricing pressure. Already, Zolgensma faces competition from Spinraza, and, more recently, Roche’s Evrysdi (newly-approved in the US and under review in Europe). Neither are gene therapies; both require life-long treatment. But they are alternatives. G-BA may not be the only European HTA body to request comparative data.

Advanced therapies can, and do, change lives for the better. That’s a good thing. But their arrival means that AMNOG’s next ten years will see it become more, not less, demanding.


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