This week's note is about a new drug, which has just been approved by the US FDA. (It has not yet been approved in the UK). The drug is called lecanemab and it is for early signs of Alzheimer's Disease. It was described in the media as a "momentous breakthrough." That massively overstated findings.
The research that led to the drug approval was a Phase 3 Randomized Controlled Trial (RCT). The drug manufacturers were heavily involved in the trial and the paper publication. The trial included 1,795 participants, with half receiving lecanemab and the other half a placebo. The study spanned 18 months and was conducted across multiple centers worldwide. Eligibility criteria were stringent, including age, cognitive status, and evidence of brain amyloid pathology through PET scans.
Initial trials showed no significant difference between lecanemab and the placebo at 12 months, with both groups experiencing cognitive decline. Lecanemab didn't reverse or halt Alzheimer's progression but claimed to slow it down slightly. On an 18-point scale, the difference between the two groups was a mere 0.45 points after 18 months. While amyloid levels were reduced as expected, it remained uncertain whether disturbing this biological pathway was advisable.
Red flags emerged regarding lecanemab’s safety. Brain scans indicated a risk of brain bleeds in 17% of participants and brain swelling in 13%. Moreover, 7% of those taking the drug had to discontinue treatment due to side effects. While some adverse events were expected given the participants' age, many were directly related to the drug and they were serious.
This trial paper was published in March 2023. A related paper was published in August 2023. This looked at the strict eligibility criteria for the lecanemab trial. Assessing patients at their own clinic in the US, researchers found that only 8% of their patients met all the inclusion and exclusion criteria. i.e., 9 out of 10 Alzheimer's patients might not be eligible for the drug.
Despite the headlines and hopes surrounding lecanemab, uncertainty still shrouds the relationship between amyloid-beta accumulation and Alzheimer's disease. Decades of drug trials targeting amyloid-beta have yielded little success. Lecanemab did not show significant results at 12 months. The drug's sponsor, Eisai Inc., played a significant role in the trial's design and analysis, raising concerns about potential bias.
Ultimately, lecanemab did not reverse Alzheimer's disease, offering only modest relief compared to the placebo, with serious safety concerns. The stringent eligibility criteria further raise questions about the drug's applicability to real-world patients. Given the risks associated with lecanemab, balancing potential benefits against these dangers is essential.