The antibody that can slow down Alzheimer’s

Late in the evening of 28 September, Lars Lannfelt received a long-awaited phone call: the phase 3 study of a drug to fight Alzheimer’s disease showed remarkably good results. Several hectic weeks ensued, with many contacts, phone calls and interviews.

“It’s been great fun, but at this point I feel rather tired,” says Lannfelt, with a smile.

We are meeting at the Rudbeck Laboratory, his base as a researcher and professor for many years. Though he reached retirement age a few years ago and is now professor emeritus, he remains active both within research and in the company BioArctic.

The study shows that the new drug can actually slow the progression of Alzheimer’s disease. As Lannfelt explains, this is something completely new.

“Drugs that alleviate the symptoms appeared in the 1990s and attempts have been made since then to use disease-modifying drugs to influence the disease progression, but with little success until now. It’s quite fantastic!”

The findings were statistically significant and the disease progression in patients with Alzheimer’s disease proved 27 per cent slower among participants in the study, compared with the control group.

“Modelling based on the data we have now suggests that we could delay the progression of the disease from one stage to another by three years, so patients could gain three years.”

Describing himself as a molecular doctor, Lars Lannfelt developed an interest early on in discovering the mechanisms behind diseases. Originally, he focused on other diseases such as schizophrenia and bipolar disorder, but after being recruited by Huddinge Hospital he began to do research on Alzheimer’s disease.

Before long, in 1992, he made his first important discovery, which American researchers called the ‘Swedish mutation’.
“In purely scientific terms, this was dynamite because it provided the first clear evidence that it was the substance amyloid-beta that caused the onset of Alzheimer’s disease. Unfortunately the patent was registered in the United States, since people in Sweden failed to appreciate the commercial value of the medical discovery.”

The next breakthrough came at the end of the 1990s. This was when Lannfelt discovered the ‘Arctic mutation’, which caused Alzheimer’s disease. The mutation was found in a family from the far north of Sweden and in 1999 the researchers began to understand the mechanisms behind it.

“It tended to increase the formation of early-stage fibrils – the long threads found in amyloid-beta plaques. This early stage fascinated me. Already back then, I conceived the idea of attempting to develop a therapy, immunotherapy, against these protofibrils.”

This time Lannfelt made sure to apply for a patent on the discovery – “kind of getting even” – which he ultimately succeeded in doing with the help of Per Svanström of Forskarpatent i Uppsala.

Around the same time he was appointed professor at Uppsala University. Funded by grants from the Swedish Research Council, the Swedish Brain Foundation (Hjärnfonden) and the Swedish Alzheimer’s Foundation (Alzheimerfonden), he moved forward with research on an antibody against protofibrils. Trials undertaken in collaboration with the Swedish company Mabtech led in 2005 to the development of a mouse antibody.

For the next step, Lannfelt started the company BioArctic along with Per Gellerfors. In collaboration with the Japanese pharmaceutical company Eisai, they developed an antibody that was adapted for human use.

Since then, the antibody has undergone three rounds of tests: a phase 1 study in 2010, a phase 2 study that ran from 2013 to 2018, and most recently the phase 3 study that began in 2019 and reported provisional findings on 28 September.

“We have worked closely with Eisai throughout,” says Lannfelt. “We provide the molecular medical and molecular biological knowledge while they have great expertise in clinical trials.”

Additional results from the latest study will be presented at a conference in San Francisco at the end of November.

“We hope and believe that this will be a registered pharmaceutical product in Sweden by late 2024. It has to go through the process of assessment and review by the medical products agencies first. That process is usually faster in the US.”

While the news of the drug has received a lot of positive press, some people think that slowing the disease progression by 27 per cent is not that much.

“You have to bear in mind this is just an 18-month study. This is a disease that has been in progress for 20 to 25 years, so you can’t expect rapid results. In this study, we are attempting to treat early Alzheimer’s but it’s still rather late in the process.”

Developing new drugs is a difficult and lengthy process, but one key factor has been patenting the idea and starting a company. Lannfelt realised this early on.

“I could never have had our collaboration with Eisai without having a patent to protect the actual principle. Moreover, it’s impossible to develop a pharmaceutical product in an academic environment. That requires a corporate set-up because large amounts of money are at stake.”

He personally has always remained focused on research. Apart from the antibody against Alzheimer’s disease, he has research in progress on the mechanisms behind Parkinson’s disease and ALS. In addition, there is research on potential ways for drugs to cross the blood-brain barrier.

“What has interested me most, really, is understanding how diseases arise, the mechanisms behind their origins. Then as I grew older, I became interested in trying to do something about it.”

In terms of the drug to fight Alzheimer’s disease, he has made considerable progress.

“I had a vision and it’s now 23 years since I had the idea. But I’ve enjoyed the journey too,” Lannfelt concludes.