The new Alzheimer’s drug Lecanemab: miracle drug or flop? Take a look for yourself!

5.4 min readPublished On: 14. December 2022By Categories: causes, forms of treatment, medication

The situation is escalating: While the number of Alzheimer’s patients in Germany and worldwide is increasing dramatically, a pharmacological breakthrough still seems to be far away. New drug candidates keep emerging that make it to the final phase of clinical approval but fail due to insufficient efficacy – and so far, not a single one has succeeded in halting mental decline.

That makes the news, which is currently running through the press, all the more worthy of attention: The new anti-dementia drug Lecanemab is said to slow down mental decline in patients by 27 percent, and the manufacturers Biogen and Eisai are currently seeking rapid market approval.

But what is really behind all this and what is the current situation on the Alzheimer’s drug market?

Immunotherapeutics, in particular monoclonal antibodies against the Alzheimer’s-specific amyloid-ß (Aß) deposits, recognizable by the suffix “-mab”, are currently on the rise. However, compounds called solanezumab (Eli Lilly) and bapineuzumab (Janssen and Pfizer) failed several years ago due to lack of clinical efficacy signals. In 2022, crenezumab and gantenerumab, two candidates from Swiss pharmaceutical company Roche, also failed to show efficacy against the fatal brain disease, and thus they too dropped out of the clinical approval process. Even the most promising drug candidate to date, Aducanumab (Biogen/Eisai), which made it to approval in 2021, albeit in a highly controversial approval process and only in the U.S., is questionable in terms of its efficacy. In Europe, its approval was rejected by the European Medicines Agency (EMA) due to “an unproven efficacy and possible serious side effects of the drug.”

The antibody Lecanumab now seems to be the new hope: the results of the clinical registration trial called Clarity-AD have not yet been published in the scientific press but are expected to be presented at the Clinical Trials on Alzheimers Congress at the end of 2022.

The clinical study with Lecanemab

In the double-blind study, the antibody agent was compared with placebo in 1795 subjects with early-stage Alzheimer’s disease with proven amyloid plaques. Administration was intravenous every 2 weeks. The primary endpoint was improvement in a standardized questionnaire, the Clinical Dementia Rating CDR-SB, compared with the beginning of the study. The CDR-SB is a 5-point rating scale that can be used to characterize six domains of cognitive and functional performance relevant to Alzheimer’s disease. For each domain, scores can be assigned from 0 (no abnormality) to 3 (severe impairment), which would sum to a maximum of 18 points for severe dementia. Under Lecanemab, scores on the CDR-SB improved by a relative 27 % at 18 months compared with placebo. This effect, according to the study, was highly statistically significant at six months.

Questionable benefit for patients

However, what sounds like high efficacy with a “27 % slowdown” and is also described by experts as “clinically relevant” is a misleading claim when looked at in more detail, and the benefit for the patient remains questionable. The reason for this discrepancy is that, at first glance, one thinks of an absolute benefit, but in fact this figure is a relative value.

The following example will explain this: A good that normally costs 100 euros is reduced by 20 euros. Then the benefit would be an (absolute) saving of €20 or 20 % of the purchase price. If the same product were only reduced by €10, one would have saved €10 less compared to the first case, or expressed relatively: 50 % less!

Transferred to the study results in the CDR-SB questionnaire, 27 % means that the patients treated with Lecanemab, as Biogen announced in a press release, performed only 0.45 points (!) better after 18 months than the control group, which had been administered a placebo! From this it can be deduced that the cognitive performance in the control group deteriorated by 1.66 points after 18 months, while the treatment instead resulted in a deterioration of 1.21 points. However, a difference of 0.5 points in the evaluation of the CDR-SB is the smallest possible difference that an investigator can document at all in an individual patient! Thus, it remains questionable what benefit this result has for the individual patient, because a difference of 0.5 points is considered very small in neurological-psychiatric practice.

Side effects and costs

As observed with other amyloid antibodies, treatment with Lecanemab also had side effects: dangerous brain swelling and cerebral hemorrhages were significantly increased in the drug group compared to the placebo group, with about 10 % of cases each. Knowing this, additional regular medical check-ups and brain imaging examinations are necessary in patients to detect the risk in time. In addition to the high therapy costs, which can be in the mid 5-digit range per year per patient, as in the example of Aducanumab, this again means a new enormous burden for the health care system.

Is amyloid-ß the right target?

As if all this were not enough: many experts agreed, at the latest after the publication of the well-known Nuns study, that Aß is not the trigger for Alzheimer’s disease. Worse still, the original amyloid hypothesis is being questioned, as has recently become known, because of possible fraud in Alzheimer’s research. It has long been known that Aß is part of the innate immune system response and has many protective functions, including protection against oxidative stress and its antimicrobial effects. Accordingly, a reduction in amyloid concentration by antibody drugs would in no way mean that the disease process can be slowed down, stopped or even reversed. On the contrary: the brain is deprived of a protective function.

Monotherapy may not be effective in multimodality disease

The patients treated in the clinical trial were initially diagnosed with high levels of technical effort and only those with Aß deposits were admitted to the study. However, in many “Alzheimer’s patients,” dementia may be due to other causes, such as stenosis of blood vessels in the brain, alcohol abuse, vitamin deficiency, etc. The US neurologist Dr. Dale Bredesen even speaks of 36 causes, which can lead to 6 different types of “Alzheimer’s disease”, which can only be approached by a multifactorial individualized concept. This makes it clear why pharmacological monotherapies are destined to fail and can neither significantly slow down, stop or reverse the disease process.


The new anti-dementia drug Lecanemab was able to slow mental decline by 27 % after 18 months in patients with early Alzheimer’s in the Clarity AD trial. However, this promising (relative) result looks rather poor in absolute terms: cognitive performance (assessed by a questionnaire with a maximum of 18 points) deteriorated by 1.66 points in the control group, and was slowed somewhat by treatment to a value of 1.21 points in the treatment group. The achieved improvement of 0.45 points (!) in the Lecanemab group compared with the control group raises the question of the benefit of this result for the individual patient, since a difference of 0.5 points in the test result is considered very small in neurological-psychiatric practice. Finally, with a rather high rate of side effects such as brain swelling and hemorrhage, and associated extra costs for the health care system, the question arises whether the amyloid ß protein is the right approach for drug development, especially since the amyloid hypothesis has been severely shaken because of suspected fraud. So Lecanemab is as much a flop as its predecessors.

All this seems almost ironic since effective, side-effect-free and significantly less costly lifestyle-oriented prevention and therapy concepts are available. Fortunately, with this knowledge, you have the choice to decide on the right therapy for your mental health!

In this spirit: Stay healthy and mentally wide awake!


  1. Söderberg L, Johannesson M, Nygren P, Laudon H, Eriksson F, Osswald G, Möller C, Lannfelt L (2022) Lecanemab, Aducanumab, and Gantenerumab – Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer’s Disease. Neurotherapeutics 2022 Oct 17. doi: 10.1007/s13311-022-01308-6.
  2. D Iacono, MD, PhD, W R. Markesbery, MD, M Gross, PhD, O Pletnikova, MD, G Rudow, BS, P Zandi, PhD, and J C. Troncoso, MD The Nun Study: Clinically silent AD, neuronal hypertrophy, and linguistic skills in early life (2009) Neurology. 2009 Sep 1; 73(9): 665–673.doi: 10.1212/WNL.0b013e3181b01077
  4. Mintun M, Lo AC, Evans CD et al. (2021) Donanemab in Early Alzheimer’s Disease. N Engl J Med 2021; 384:1691-1704, DOI: 10.1056/NEJMoa2100708

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Photo by Dimitri Karastelev on Unsplash

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