Nobody can with Alzheimer’s: the most promising therapy against the disease fails

Roche has been forced to suspend the Phase III trials it was carrying out with gantenerumab, a molecule that was considered to be the most promising bet

The fight against Alzheimer’s is something of a roller coaster. The disease continues to escape the increasingly successful attempts of science to stop its progression . The knowledge of new biological factors that lead to the progressive deterioration of neuronal function is combined with resounding failures in clinical trials with possible therapies. It is the face and the cross of an epic fight against one of the most elusive pathologies that exist. In recent weeks, the frenzy of both good and bad news has produced two big headlines.

In the corner of hope, a team of researchers from the Institut Hospital del Mar and the Barcelona Beta Brain Research Center announced in the journal “Alzheimer’s and Dementia” the discovery of nine possible biomarkers in blood related to the Tau protein and that could be useful for early diagnosis of disease. Based on the performance of simple tests, these markers were able to detect Alzheimer’s with an accuracy close to that of the clinical reference test that is currently the lumbar puncture. Therefore, they can function as a diagnostic marker, even in the first moments of the disease, advancing the moment in which doctors, patients and relatives are aware of the disease they are facing. In the absence of a cure, the early diagnosis of the pathology becomes a fundamental tool for clinical practice and for improving the quality of life of the patient, and of their family and social environment.

But the great Achilles heel of the battle against Alzheimer’s remains the cure . Despite the fact that science has more and more knowledge (although still incomplete) of the genesis of neuronal deterioration typical of this syndrome, the therapeutic attack is still far from being feasible . And in that direction the latest failure of a pharmaceutical company has fallen like a bucket of cold water. Roche has been forced to suspend the Phase III trials that it was carrying out with gantenerumab, a molecule that was considered to be the company’s most promising bet to achieve an anti-Alzheimer drug. The drug has failed in its ability to halt functional and cognitive decline in patients.In 2014, another similar trial had also yielded poor results. Still, the Swiss drugmaker was hopeful that it could resurrect the drug with a new batch of tests. The idea of ‚Äč‚Äčthis second attempt was to demonstrate a significant reduction in clinical deterioration in a large group of patients measured by the CDR-SOB index (Clinical Dementia Rating Scale Sum of Boxes), a common tool for determining the degree of dementia.

But the work carried out on a base of 2,000 patients studied for more than two years has shown a statistically insignificant reduction in the affectation (between 6 and 8 per 100 compared to placebo). Although the company will present new definitive data, the result that is known so far is far from being considered encouraging. Especially with regard to the disappearance of the accumulation of Beta-amyloid protein, which has been less than expected. The alteration of the behavior of Beta-amyloid has been considered for a long time as one of the causes of Alzheimer’s disease, although it is true that the theory has received some criticism recently.

The words of Levi Garraway, Roche’s medical director, leave no room for doubt. In an official statement he has described the news received from the trial as “very disappointing”.

Gantenerumab is a fully human monoclonal antibody that is administered subcutaneously and is designed to target and bind aggregated forms of Beta-amyloid. Once there, it intends to activate the cells of the brain’s immune system so that they react by avoiding the protein plaques and stopping their accumulation. In theory, it is the excess presence of this Beta-amyloid protein that generates the famous plaques that hinder the correct function of neurons.

There has been no luck: the drug has not been shown to be really effective in this protective task.

Some analysts have claimed that this failure clears the way for other competing molecules to Roche’s. But the truth is that today no alternative seems solid enough.The only FDA-approved drug (Biogen’s aducanubab) remains embroiled in controversy. The company withdrew the authorization request by the European Medicines Agency in May. Although the molecule did prove effective in stopping the concentration of Beta-amyloid, the real improvements in the cognitive health of patients were considered insufficient.

The third in contention is another Biogen drug (lecanemab), an antibody that seems to have given statistically relevant results and is rumored to be approved as early as 2023.

But in recent days it has suffered a considerable setback. The death of a patient included in one of the trials hit the media a few weeks ago. The authors of the study assure that the death is not related at all to the molecule. But it is one more of the shocks that seem to accompany the scientific battle against this devastating disease.