Btobioinnovation.com 

Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation  jcm9144@gmail.com

SPECIAL REPORT #22.13

Lecanemab shows positive outcomes in Alzheimer’s disease

On September 28, Eisai and Biogen issued a press release where they announced that lecanemab, an investigational anti-amyloid beta protofibril monoclonal antibody, discovered by Bioartic Neuroscience in Sweden, had shown significant reduction of clinical decline in patients with early Alzheimer’s disease. In the phase 3 Clarity study, which included 1,795 participants, lecanemab met the primary endpoint and reduced decline on the global cognitive and functional scale compared with placebo at 18 months by 27%. Like many others we are waiting to see the full study results which will be presented on November 29, 2022, at the Clinical Trials on Alzheimer’s Congress (CTAD)

This statistically significant reduction of clinical decline is good news for Eisai and Biogen after the controversial approval by the US FDA of Aduhelm on June 7, 2021, and finally its major commercial setback later in the year. It is also good news for Eli Lilly and Roche which develop similar drugs targeting beta amyloid. And it is excellent news for the eight million people suffering from Alzheimer’s disease.

The Clarity AD study is the first large study targeting beta amyloid, with a positive clinical outcome

What is next?

As already indicated the medical community is waiting to see the full results of the Clarity study when they will be presented at the CTAD in November.

Eisai indicated that it would file these additional data with regulatory authorities in the U.S, Japan and Europe before March 31, 2023.

If late-stage data from Lilly for donanemab and from Roche for gantenerumab are also positive, clearly the amyloid hypothesis, which targets the abnormal accumulation of amyloid beta in the brain, will finally be proven and as Maria Carillo, Alzheimer’s Association Chief Scientific Officer said: “This is the time we will look back and say”. “That was when it all started”.

In the July-August 2021 issue of MedNous, where we commented the various ongoing Alzheimer’s disease studies, we had indicated that researchers are already trying new approaches which go beyond plaque destruction. If lecanemab, donanemab and gantenerumab, which each target a different pathway of amyloid, are also approved, “they will pave the way for innovative clinical studies where these antibodies will be combined with agents which restore synaptic plasticity, insulate neurons form injury, activate microglial function and remove debris from Alzheimer’s brains.” Haruo Naito, Chief Executive Officer at Eisai stated :“Eisai believes these findings (the Clarity AD study) will create new horizons in the diagnosis and treatment of Alzheimer’s disease as well as further activate innovation for new treatment options.”

The regulatory authorities will certainly scrutinise the ARIA side effects of lecanemab. ARIA is an important adverse event of amyloid-lowering therapies that needs to be monitored and managed during treatment. ARIA is most commonly seen as temporary swelling/effusion (ARIA-E) but sometimes associated with cerebral microhaemorrhages, microhaemorrhages and superficial siderosis in the brain (ARIA-H). The total incidence of ARIA (ARIA-E and/or ARIA-H) was 21.3% in the lecanemab group and 9.3% in the placebo group. Real world evidence data on many more patients will be necessary to make sure that these adverse effects are not associated with major symptoms for already frail Alzheimer’s patients.

There is a very high probability that the U.S. FDA will approve lecanemab in the first quarter of 2023. The community will also dedicate great attention on the price Eisai and Biogen will be setting for the drug. In July of 2021, Biogen had set a price of $56,000 for one year’s supply of Aduhelm in the U.S. when bodies such as the Institute for Clinical and Economic Review (ICER) had determined through modelling that the price should be between $2,500 and $8,300 per patient per year. It proved later that this price tag was a major management mistake.

Paris, October 14, 2022

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