Lecanemab for early-stage Alzheimer’s disease: Previously unpublished data show no added benefit

Lecanemab has been available in Germany for the treatment of early-stage Alzheimer’s disease since September 2025. The drug is intended to slow the progression of the disease and must only be used in adults who

• have mild cognitive impairment or suffer from mild dementia,
• exhibit typical protein deposits (amyloid-beta plaques) in the brain and
• carry at most one copy of the ApoE ε4 gene variant in their DNA.

The German Institute for Quality and Efficiency in Health Care (IQWiG) has now examined in a benefit assessment whether lecanemab offers benefits over the present standard of care for these patients. For patients with mild cognitive impairment (MCI), the Federal Joint Committee (G-BA) specified ‘watchful waiting’ as the appropriate comparator therapy, also because there are currently no approved drugs available for this group. Treatment with acetylcholinesterase inhibitors is the current standard of care for people with mild Alzheimer’s dementia.

For both patient populations, IQWiG concludes that there is no proof of added benefit lecanemab compared with the current standard of care in Germany.

“Our assessment is based on previously unpublished data which the manufacturer was required to provide in its dossier. Thanks to the high level of transparency in the German AMNOG procedure, these are now also available to the public,” explains Daniela Preukschat, Head of the Chronic Diseases Division in IQWiG’s Drug Assessment Department. “However, the data still leave some questions unanswered, as further relevant information was missing in the dossier.”

The comparison with the standard of care in Germany is decisive

Selected results from the pivotal lecanemab approval study CLARITY AD were published in 2023. Since then, experts and the general public have been discussing, above all, these originally published data on the study’s total population. The study demonstrated that lecanemab slows cognitive deterioration compared with the control group. However, due to serious side effects, the European regulatory authority has significantly restricted the therapeutic indication of lecanemab, meaning that these original findings – which are still the subject of debate today – are no longer decisive. Moreover, a comparison with the German standard of care is also crucial for use in Germany. On the one hand, the assessment therefore focused on the on-label use of lecanemab and, on the other hand on a comparison with the standard of care in Germany.

Preukschat explains: “The positive effects of lecanemab in the total study population are primarily attributable to those patients who were not treated in accordance with the German standard of care. However, the relevant analyses show no advantage of lecanemab. And this information is now available for the first time."

It is also striking that the study did not examine the important question of whether lecanemab is superior to acetylcholinesterase inhibitors in cases of mild Alzheimer's dementia. The study design only provided an investigation of the use of lecanemab as an add-on therapy to existing treatment with acetylcholinesterase inhibitors; however, lecanemab monotherapy was not compared with acetylcholinesterase inhibitors. The CLARITY-AD study therefore fails to address a key issue relating to care.

Further key data are missing

Although the dossier contains previously unpublished data, some important data are still missing. In particular, the dossier does not include analyses of important side effects, i.e. the symptomatic ARIA events, for the populations of interest.

“This assessment clearly demonstrates how important an independent assessment, based on all available information, is and remains. This is the only way that individuals with early-stage Alzheimer’s dementia can make the appropriate decision for themselves in difficult personal situations,” says IQWiG Director Thomas Kaiser, summarizing the results of the benefit assessment. “We are keen to see whether the manufacturer will now present the missing data to the G-BA as part of its comments.”

The G‑BA decides on the extent of the added benefit

The dossier assessment is part of the early benefit assessment in accordance with the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G‑BA. After publication of the dossier assessment, the G‑BA conducts a commenting procedure and makes a decision on the extent of the added benefit.