What was the motivation behind your commitment to develop a treatment for Alzheimer's disease?

Dr. Sugimoto : My mother developed dementia in her later years. Whenever I went to visit her, she'd ask me, “Young man, who are you?” It was a shock to me that my mother could no longer recognize her own son. I would say to her, “Mom, it's me, your son Hachiro,” and she'd reply, “Oh, you don't say? My son's name is Hachiro. You both have the same name.” It was a very sad time for me and I found it difficult to accept the reality of the situation. With these memories of my mother playing in my mind, I felt inspired that it was my mission as a scientist to generate an effective new drug for Alzheimer's, despite the illness' notoriety for being one of the most difficult-to-treat diseases.

What were some of the thoughts running through your mind during the initial conceptualization stage that led to Aricept's creation?

Dr. Sugimoto : My mother eventually passed away from dementia-related causes and that had a huge personal impact on me. Being a scientist who works in a pharmaceutical company by profession, I knew then that I wanted to create a drug for treating Alzheimer's disease.

Research for Aricept first began in 1983. At the time, there was a hypothesis that suggested that neurotransmitters in the brain called acetylcholines were closely linked to abnormal decreases in memory function in patients with Alzheimer's disease. It was stubborn perseverance on our part in regard to the acetylcholine deficiency hypothesis that ultimately enabled us to bring the project to fruition.

It must have been a long journey trying to create the right compound for development. What was that process like?

Dr. Sugimoto : During the time when I was the leader of the E2020 (Aricept) project team, the acetylcholine deficiency hypothesis had already gained a certain level of recognition, but there were also opposing views that proposed that the hypothesis could turn out to be a failure.

The discovery of our seed compound was by mere coincidence. We came across the compound during random screening when searching for compounds that possessed inhibitory activity for acetylcholinesterase, which is an enzyme that breaks down acetylcholine. The compound had previously been synthesized with a different purpose in mind but, surprisingly, it ended up leading the way to the creation of Aricept.

Next, we further developed our seed compound through chemical synthesis and in 1985 generated a new lead compound with still-higher efficacy. Unfortunately, the compound was later found to have problems related to its pharmacokinetic profile such as low bioavailability, but after further attempts to overcome this issue, we were able to successfully create E2020 (Aricept) with a promising enough profile for the compound as a drug candidate. In March 1987, Eisai formally decided that the project would take the next step in its development.

What were some of the expectations of those around you during the R&D phase in regard to the project?

Dr. Sugimoto : Looking back on other Eisai products that have gone on to become blockbuster drugs, such as Juvela Nicotinate, Neuquinon and Methycobal, you could say that expectations during the R&D phase for those drugs were actually on the chilly side. In any drug development, you see, it's quite difficult for things to simply sail smoothly from day one.

With new drug development, you'll often have one person who has stuck to a particular idea very passionately—even obsessively. I think that one key success factor is that that person is provided support both explicitly and implicitly from top management and all teams involved in the project. The same applied to E2020—top management was there to keep an optimistic eye over things to balance out the more reserved expectations from others on the whole.