“The beginning of a new era”

In the summer, the EMA, the European Medicines Agency, initially rejected approval for the Alzheimer's drug Lecanemab. Now, the medication has been approved after all. What led to this reversal?

The EMA's decision was already controversial back in the summer. As researchers at the DZNE, we even openly criticized it. At that time, the commission initially concluded that while the individual benefits of the new drug were evident, they were counterbalanced by potentially severe side effects. Following this, the company aiming to market the drug in Europe submitted additional data from the approval study. These findings were not new, but the manufacturer excluded a group of patients from the analysis who were at particularly high risk of side effects. These patients carry a specific genetic variant that increases the likelihood of adverse effects. For many others, however, the risk-benefit balance appears more favorable. Consequently, the EMA decided to recommend approval, restricting treatment to individuals without the critical genetic variant.

How significant is this step for the treatment of Alzheimer’s patients?

This is a game-changer, marking the beginning of a new era! For the first time, we have a therapy available that targets not just the symptoms of the disease but its underlying causes. Lecanemab is an antibody that combats the plaques forming in the brains of Alzheimer’s patients. This allows us to positively influence the progression of the disease in the long term – truly a medical breakthrough.

However, the individual benefits are still limited.

That’s true. The drug slows memory loss by about 27 percent. But this is just the beginning of the development process. In the future, new medications with more advanced antibodies will be introduced, offering even greater efficacy. We are also likely to see the emergence of combination therapies. It’s worth noting that this approval will also stimulate Alzheimer’s research. Scientists have been investigating the causes of Alzheimer’s for decades, and at the DZNE, we’ve been doing so since our foundation 15 years ago. It’s been a long journey, involving genetic analyses, animal models, biomarker research, and much more, leading to the identification of one of Alzheimer’s key causes: plaque-forming amyloid proteins. For over 20 years, research has been working to develop drugs to counter these proteins. Achieving this success demonstrates that perseverance, the efforts, and the energy of the scientists have paid off. It also shows that the funding provided over decades by Helmholtz and other third-party sponsors for Alzheimer’s research was a valuable investment.

What must happen now to ensure patients can access the new medication as quickly as possible?

The therapy with Lecanemab requires some preliminary examinations. First, it must be confirmed without a doubt that the patient has Alzheimer’s disease. Lecanemab is only suitable for the early stages of this type of dementia, used when the first neurological memory deficits appear in daily life. However, these symptoms can have other causes, which we must rule out beforehand.

How is this done?

These tests provide an initial indication of memory loss. In the second step, we analyze either the cerebrospinal fluid or the brain to detect amyloid proteins responsible for Alzheimer’s. These procedures are relatively complex: we collect cerebrospinal fluid through a lumbar puncture or perform PET scans, which use radioactive tracers to make brain deposits visible. Only when both tests point to Alzheimer’s – the memory test and the amyloid detection – can we be certain that the patient is a candidate for treatment. Even then, we must remain vigilant about potential side effects.

Are these sufficient for a definitive diagnosis?

These tests provide an initial indication of memory loss. In the second step, we analyze either the cerebrospinal fluid or the brain to detect amyloid proteins responsible for Alzheimer’s. These procedures are relatively complex: we collect cerebrospinal fluid through a lumbar puncture or perform PET scans, which use radioactive tracers to make brain deposits visible. Only when both tests point to Alzheimer’s – the memory test and the amyloid detection – can we be certain that the patient is a candidate for treatment. Even then, we must remain vigilant about potential side effects.

How do you address these risks?

Studies show that the risk of side effects is particularly high in patients who have two copies of the ApoE4 gene. The EMA has excluded these individuals from treatment with Lecanemab. Alzheimer’s patients must, therefore, undergo genetic testing. There are additional contraindications: patients on specific blood thinners are also excluded due to an increased risk of brain bleeding. All patients must also undergo MRI scans to detect microbleeds in the brain – these may go unnoticed by the patient. However, if the scans show more than two microbleeds, treatment with Lecanemab is not advisable due to the high risk of bleeding.

The preliminary examinations are extensive. Does this mean treatment will only be possible in specialized clinics?

No, larger non-university hospitals, memory clinics, or specialized practices can also provide this treatment. However, a certain level of specialization and expertise will be necessary. I think the care model will develop similarly to specialized chemotherapy for cancer: not every general practitioner’s office can offer it.

When do you expect the first patients to receive an infusion?

We will likely be ready as early as the first quarter of the coming year, probably by February.

Will health insurance cover the costs?

That’s still unclear, as the price of the drug has not yet been determined. Negotiations with the Joint Federal Committee now need to begin. Additional costs will arise from the preliminary examinations, such as MRI scans. During the treatment, further MRIs – at least four – are required to ensure no brain bleeding occurs. I expect that health insurers will eventually cover the treatment costs.

How many patients might qualify?

This remains to be seen. Looking solely at genetics and the EMA’s restrictions, Lecanemab could be suitable for about 80 percent of Alzheimer’s patients in the early stages of the disease. For other patients, we hope to have additional drugs and therapies available in the future.

Which ones are you particularly optimistic about?

I anticipate that several new treatments will emerge in the coming years. For example, another manufacturer has already applied for approval of an antibody that also targets amyloid proteins. The EMA will likely make a recommendation on this in the near future. Moreover, antibody therapies can still be improved to enhance their efficacy and reduce side effects. Research is underway on tiny shuttle systems that could deliver antibodies more precisely to the brain than current methods.

Are there alternative approaches beyond amyloid antibodies?

Another protein, known as Tau, also triggers Alzheimer’s. Early studies have shown that certain drugs targeting Tau can slow disease progression. Combination therapies are also promising: in the future, we could use medications containing antibodies for both amyloid and Tau. These might even be combined with drugs from entirely different fields: for example, new weight-loss injections seem to have a positive effect on Alzheimer’s progression. Non-drug interventions could also be part of these combinations – Alzheimer’s responds well to them.

What non-drug interventions are most effective?

Reducing cardiovascular risk is crucial, such as managing high blood pressure or treating heart rhythm disorders. Addressing hearing loss or vision impairment and maintaining a healthy diet are also important. Psychosocial factors play a key role – Alzheimer’s patients should avoid isolation, engage with others, and stay active. One promising approach is Dementia Care Management (DCM), which the DZNE is advancing. In this model, specially trained caregivers coordinate the at-home care of Alzheimer’s patients, collaborating with families, medical professionals, and psychosocial therapists. Scientific studies show that DCM works: while it doesn’t address the root cause of the disease, combining it with new drugs could lead to highly effective therapies.

European Medicines Agency recommends approval of novel Alzheimer's drug (DZNE)