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Todays’ blogpost begins with a petition I have signed, and which I’d encourge you to read, sign and share. Please. People with dementia should not be harmed by drugs that are fast tracked for approved, after accelerated drug trials, and which are known to be unsafe.
People with dementia are not lab rats or mice.
Lecanemab is neither safe nor effective for Alzheimer’s patients: Against the FDA approval
Read some of the reasons why this petition is so important.
To back up why I support this petition, I am also sharing a short article by a colleague Markku Kurkinen © written on 6/17/2023 which further highlights the dangers to people with dementia, of the acceleration of drugs for Alzheimer’s Disease and potentially other dementias. I met Markku in Taiwan in 2013, and again in Budapest in 2016 at ADI conferences, and we have stayed in contact by email since. Markku is a Professor at the Wayne State University School of Medicine, Detroit, Michigan, in the USA.
One point made in this article (scroll down to read it), is that ‘even if lecanemab worked for men, it certainly did not work for women.”
We already know dementia disproportionately affects more women and girls than men, so one has to wonder, are women also facing sexism within pharmaceutical research? Definitely food for thought…
The other concern to me, is that these drugs were heavily endorsed by the international and national dementia charities, some who receive significant funding from big pharma, hence they have major conflicts of interest. Many other organisations and individuals, including academic and clinical ‘experts’ also support it, though we have no way of knowing how much money from big pharma goes to researchers; there is a lack of transparency around this topic. There is an increasingly thriving dementia industry, and it is obvious there is big money in dementia, that is, except for people with dementia. This is despite the fact there is such poor access to a diagnosis and none, or very little access to post diagnostic care and support.
Another article, Fatal outcome in trial of Alzheimer’s drug lecanemab raises patient safety concerns, provides further evidence of how unsafe these drugs are. And because we’re on the topic of harmful drugs for people with dementia, this article Does a Pill Really Make a Difference?, is also worth reading, further highlighting the need to #BanBPSD.
The following article by Markku Kurkinen © 17 June 2023, was first published here.
On January 6, the US Food and Drug Administration (FDA) granted an accelerated approval of lecanemab (branded Leqembi by Biogen and Eisai) for the treatment of early Alzheimer dementia (AD) patients. On June 9, six voting members of the FDA’s Peripheral and Central Nervous System (PCNS) Drugs Advisory Committee endorsed 6-0 the full approval On July 6, the FDA approved lecanemab. The approval was based on the results of the clinical trial Clarity AD published in the van Dyck et al, (2023) paper (“the paper”), which showed lecanemab reduced amyloid in the brain and slowed cognitive decline of the AD patients [1]. The purpose of this letter is to demonstrate that the trial results provide no evidence for lecanemab’s efficacy in slowing cognitive decline.
Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) measures cognition and function on a 0-18 points scale, higher scores indicating worse performance. The paper states “A total of 1795 participants were enrolled, with 898 assigned to receive lecanemab and 897 to receive placebo. The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference -0.45).
Importantly, -0.45 (and 1.21 and 1.86) are not measured values (which is not obvious or explicitly stated in the paper) but calculated from the difference -0.20 for women (52.3%) and -0.73 for men (47.7%), which are shown in Fig. S1B (Supplementary Appendix). -0.45, for example, is the weighted average of -0.20 and -0.73, calculated as 52.3 x (-0.20) + 47.7 x (-0.73) = -0.45.
Most importantly, -0.20 and -0.73 are too different to originate (statistically) from the same population, but rather from two different populations centered around -0.20 and -0.73. Therefore, -0.45 does not characterize any population, does not represent anybody, it’s useless, and has no meaning.
-0.45 is often expressed as 27% (0.45/1.86) and branded as lecanemab’s clinical benefit in slowing cognitive decline in early AD patients. When -0.45 has no meaning, 27% has no meaning. As shown by Kurkinen et al. (2023), lecanemab’s clinical benefit is 9.3% (0.45/4.86),including baseline 3.2, which is unlikely to make any difference in the real life of AD patients [2,3]. Finally, even if lecanemab worked for men, it certainly did not work for women.
APOE4 is the biggest genetic risk factor of AD. It increases the risk, lowers the age of onset, and enhances the development and progression of AD [4]. One APOE4 gene (12% of population) increases AD risk 2-fold and two (2% of population) 12-fold.The effects of APOE4 in the Clarity AD trial are given in Fig. S1B, which shows CDR-SB score differences between lecanemab and placebo groups as -0.75 for individuals without (-/-), -0.50 with one (+/-), and 0.28 with two (+/+) APOE4 genes. Of note, the 0.28 difference indicates lecanemab enhanced cognitive decline of AD patients with two APOE4 genes (15.5% of study population), the group of people in the most need for treatment and prevention of AD. Of note, from the data on the % slowing of decline, shown in Fig. S1B, we can calculate CDR-SB score increase from baseline to 18 month in the placebo group as 1.83 for (-/-), 1.67 for (+/-), and 1.27 for (+/+) individuals, indicating slower dementia progression in APOE4 carriers compared to non-carriers. For example, 1.27 – 1.83 = -0.28 would indicate that having two APOE4 genes is associated with 15% slower cognitive decline (0.28/1.83) in 18 months. Assuming the same 3.2 baseline regardless of the APOE4 status (not given in the paper), two APOE4 genes would provide a 5.6% (0.28/5.03) ‘protection’ against dementia progression Needless to say, these data are against what is known about APOE4 in the development of AD [4].
In conclusion, there is no evidence-based science to show lecanemab has clinically meaningful benefit in slowing cognitive decline.
On the contrary. The use of lecanemab (and other anti-amyloid monoclonal antibodies) in clinical trials has consistently resulted in serious adverse events of ARIA, or amyloid related imaging abnormalities, seen in MRI pictures and caused by brain swelling and brain bleeding in AD patients that can be fatal [5,6].
Therefore, we ask the European Medicines Agency (EMA) reject the approval of lecanemab for the treatment of early Alzheimer dementia patients.
References
- van Dyck et al. (2023) Lecanemab in early Alzheimer’s disease. New Engl J Med 388:9-21,
- Landsdall et al. (2023) Establishing clinically meaningful change on outcome assessments frequently used in trials of mild cognitive impairment due to Alzheimer’s disease. J Prev Alzheimers Dis 10, 9-18
- Kurkinen, M, Fułek M, Fułek, K, Beszłej JA, Kurpas D, Leszek J (2023). The amyloid cascade hypothesis in Alzheimer’s disease: should we change our thinking? Biomolecules 13, 453
- Raulin et al. (2022). ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies. Mol Neurodegener 17:72
- Espay AJ, Herrup K, Daly T (2023). Finding the falsification threshold of the toxic proteinopathy hypothesis in neurodegeneration. Handb Clin Neurol 192:143-154
- Castellani RJ, Shanes ED, McCord M, Reish NJ, Flanagan ME, Mesulam MM, Jamshidi P (2023) Neuropathology of anti-amyloid-β immunotherapy: a case report. J Alzheimers Dis 93, 803-813.
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