Alzheimer’s Therapy Elenbecestat Reduces Brain Amyloid Levels, is Safe and Well-Tolerated, Trial Shows

Alzheimer’s Therapy Elenbecestat Reduces Brain Amyloid Levels, is Safe and Well-Tolerated, Trial Shows

Treatment with the investigational compound elenbecestat reduced brain amyloid beta levels and was safe and well-tolerated, according to Phase 2 clinical trial results.

The presence of amyloid beta plaques is a major characteristic of the brains of Alzheimer’s disease patients. Amyloid beta is produced through the work of a key enzyme called BACE (beta-amyloid cleaving enzyme). Elenbecestat is an oral inhibitor of BACE being developed by by Eisai and Biogen.

The multicenter randomized, double-blind Phase 2 trial (NCT02322021), also known as Study 202, is assessing elenbecestat in patients with mild cognitive impairment (MCI) due to Alzheimer’s, or with mild-to-moderate dementia also due to Alzheimer’s, with amyloid beta buildup confirmed by positron emission tomography (PET) imaging.

Seventy patients were enrolled and randomized to one of four groups receiving either 5, 15, or 50 mg of daily elenbecestat, or placebo.

More than half of the patients who received 5 and 15 mg of elenbecestat switched to 50 mg for three months or more, representing a total of 38 subjects taking the higher therapeutic dose for a mean duration of nearly 11 months.

Patients receiving 50 mg elenbecestat showed a significant decrease in brain amyloid beta level over 18 months in comparison to placebo.

Cognitive function assessed with CDR-SB (Clinical Dementia Rating Sum of Boxes), a commonly used scale of dementia severity, and with ADCOMS, Eisai’s newly developed scale, revealed a slower decline in cognitive function, although not statistically significant.

According to both companies, this is the first study of a BACE inhibitor to show a statistically significant difference in amyloid beta in the brain while also suggesting a delay of clinical symptom decline in exploratory goals.

The most frequent problems observed in patients taking the highest does of elenbecestat included dermatitis (skin inflammation), upper respiratory infection, diarrhea, headache, and falling. No serious reactions suggesting liver toxicity were observed.

“It is highly encouraging that Study 202 confirmed elenbecestat’s treatment effect in reducing amyloid in the brain and suggested a slowing of clinical decline,” Lynn Kramer, MD, said in a press release. Kramer is chief clinical officer and chief medical officer (CMO), Neurology Business Group, at Eisai. Tokyo-based Eisai is planning to present detailed results at a future medical meeting.

“Biogen is heartened by the safety and tolerability results of this study of elenbecestat,” Alfred Sandrock, MD, PhD, executive vice president and CMO at Biogen, said as he reaffirmed the company’s committment to research in Alzheimer’s.

Besides their collaboration in the development of elenbecestat, Eisai and Biogen also are conducting the Phase 2 Study 201 (NCT01767311), as well as two global Phase 3 trials in early Alzheimer’s: MissionAD1 (NCT02956486) and MissionAD2 (NCT03036280).

Both these studies are recruiting participants.


  1. Jim Deitrick says:

    My wife is 71 and is in the moderate to final stages of AD. Under the newly passed Right To Try Law is this something that she can ask for?

    • Saralee Perel says:

      Hi Jim,

      I too have a question about this medication, but I don’t see a place where I can ask a question. I would try here, like you did, but would first appreciate hearing from you, as to whether or not you received a response to your question.
      Thank you in advance. My name is Saralee Perel and the way to respond, if you’d please, would be to email me at: [email protected]

    • dennis damato says:

      my wife is 71 and has been diagnosed with alzheimers is there an on going study and how do we find out where and when

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