Reacción a "EMA recommends not to approve lecanemab against Alzheimer's disease"

I consider the decision taken by the EMA to be very negative. Basically two aspects are alluded to: the debatable clinical relevance of the effects and the side effects. Lecanemab has provided solid evidence of its biological effect that corresponds to moderate clinical efficacy in slowing down the progression of the disease in very early symptomatic phases. The clinical impact may seem small, but this is very relative: the results we have are only at 18 months and in patients with such a mild clinical situation a change of 0.5 points on a scale (CDR-SOB) on which the average score is 3.2 at the time of starting treatment (the scale goes from 0 to 18, the higher the score, the worse the clinical condition) means a slowing of progression measured on this scale of 30%.

Who are we to judge whether 6 months more in a clinical situation of mild cognitive impairment (patients who are independent) is too little or too much? We agree that we would all like it to be more, but it is not a negligible change.

But the reason for the rejection is not so much the small clinical efficacy as the potential side effects. In a small percentage of patients (0.8% of serious adverse effects in the CLARITY trial) they are serious (even in a small number of patients they can be fatal). According to the EMA this is not assumable, and this is where the most controversial part lies. Most of these effects appear in ApoE e4 homozygous carriers (15% of patients) or in anticoagulated patients. The first two aspects can be known before starting treatment, they can be discussed with the patient and his family, and a consensual decision can be made, taking into account his personal situation and his wishes (where is the patient's right to autonomy?). Or even its use could be restricted for this group of patients until more safety data are available. But no, the EMA has gone with the broad brush and has unceremoniously denied it. In a veiled way, it is implied that the economic impact of the introduction of these treatments and the modifications that would have to be made to implement them does not compensate. Unfortunately, I believe that, in the end, this is what has prevailed.

My personal view of these treatments is as follows. They are not a panacea, but there are groups of patients who can benefit from them with a low (and acceptable) rate of side effects. And we cannot deny them that opportunity, it is unethical. We are providing treatments for incurable diseases, such as some cancers, which are much more toxic and dangerous. It is the patient who, faced with his or her clinical situation, with no other options, decides, advised and accompanied by the medical team attending him or her. This is a neurodegenerative disease without treatment, don't our patients deserve the opportunity to decide if it is worth the risk with minimum guarantees? Are Alzheimer's patients second-class patients?

Well, if this is clear to us, let us put in place the measures to get it right: a European registry of all patients treated in specialized centers, with experience in the use of antiamyloids, which can ensure a correct indication and adequate monitoring of side effects. In this way we will obtain the evidence of its long-term effect, since we will only obtain it from real clinical practice. No private laboratory is going to pay for a clinical trial of 5 or more years, which is what would really be needed to see major effects (this has already been modeled for some time). With this decision we will leave this data to be provided by the clinical experience of the other countries where it has already been approved. Or from wealthy Europeans going to the US for treatment, as John Hardy has commented. Our patients will have to wait at least 4-5 years for this and it will already be too late for them.