The ADDF scientific affairs team and I recently participated in the 13th Clinical Trials on Alzheimer’s Disease (CTAD) conference. Conferences like CTAD are a vital way for the scientific community to come together and share knowledge to help move the Alzheimer’s research enterprise forward, which is why the ADDF is also a proud conference sponsor.
The goal of CTAD is perfectly aligned with our own: to overcome the hurdles and speed the development of effective Alzheimer’s treatments. Among this year’s key topics was the global effort to identify new biomarkers of Alzheimer’s disease, which is also the aim of the ADDF’s Diagnostics Accelerator (DxA).
I had the pleasure of hosting two CTAD sessions on biomarkers. One focused on the latest advances in blood and imaging biomarkers of tau and the other was a progress report from our Diagnostics Accelerator. I co-hosted the latter with Niranjan Bose, Ph.D., Managing Director of Health & Life Sciences at Gates Ventures, and we were joined by a panel of world-class experts.
Simon Lovestone, Ph.D., who leads a team at Janssen Pharmaceuticals studying novel therapies for neurodegeneration, echoed the ADDF’s view that biomarkers are critically important for accelerating progress in clinical trials. In his words, the “age-old mantra of no drug development without an accompanying biomarker,” is an absolute for today’s Alzheimer’s trials. He also said that “one biomarker is not going to rule them all. We will need many.”
The first goal is for biomarkers to improve the way we do clinical trials. The ultimate goal is that they work so well in clinical trials that they can be transitioned easily into clinical patient care.
Dr. Lovestone also highlighted Janssen’s role in the Diagnostics Accelerator Biobank Sharing Program. Janssen and its partner Shionogi recently made patient samples collected from earlier clinical studies available to qualified researchers through the ADDF Biobank. Our agreements with Janssen/Shionogi, Roche, and Eisai have created one of the largest and most valuable biobank sharing programs of blood and cerebral spinal fluid specimens from Alzheimer’s patients.
In his opening remarks, Dr. Bose reminded us that the growing burden of Alzheimer’s necessitates that we accelerate ways to diagnose the disease early and then intervene and monitor its progression. Rapidly advancing technology is opening new doors for digital biomarkers that can achieve this.
Rhoda Au, Ph.D., Professor of Anatomy and Neurobiology, Neurology, and Epidemiology at Boston University Schools of Medicine and Public Health, agreed that the first goal is to develop digital biomarkers for early diagnosis, but she went a step further, saying she hopes digital biomarkers will eventually be prognostic. This will give people with Alzheimer’s and their families time to implement prevention strategies before symptoms even begin.
Dr. Au and her colleagues have deployed a smartphone app to collect a large pool of data about Alzheimer’s behaviors among older people. The data includes changes in cognition, walking, balance, mood, and depression. Her team will use advanced data science tools to aggregate and analyze the data to develop digital profiles to help medical professionals differentiate among patients with stable cognition, cognitive decline, and dementia.
Henrik Zetterberg, M.D., Ph.D., Professor of Neurochemistry at the University of Gothenburg in Sweden, told the audience that the last two years have been the most exciting time in Alzheimer’s disease blood biomarkers. Advances by multiple research groups are showing similar results, which is a key step in scientific trials. When we see the same patterns emerge, our confidence in the results grows.
Dr. Zetterberg also discussed how important the DxA has been to his research. As part of its due diligence before making awards, the ADDF’s scientists perform a thorough assessment of the research. The ADDF assessment and positive findings made it possible for his commercial partners at Roche to secure additional, vital research funding.
The long-term goal, said Zetterberg, is to make the blood tests “super easy to implement” and very precise. This takes time, money, and collaboration. He reminded the audience that early total tau assays could not differentiate Alzheimer’s from other dementias. Over time, researchers zeroed in on specific types of tau versus total tau, and functional biomarkers have emerged. These were the subject of the second session I led.
Jeffrey Dage, Ph.D., Research Fellow at Eli Lilly, discussed recent advancements that have made it possible to accurately and precisely measure phosphorylated tau, or P-tau, in blood samples, which may be elevated for years before Alzheimer’s disease symptoms begin. Given the simplicity a blood test offers, the p-tau 217 test is being broadly explored for use in clinical trials.
Michael Devous, Ph.D., Vice President at Avid Radiopharmaceuticals, discussed how tau brain imaging is already being used in clinical trials. Accumulation of tau in the brain is closely associated with neurodegeneration and synaptic dysfunction, and mirrors clinical changes including increased cognitive impairment and decreased ability to perform day-to-day tasks. Therapeutic trials now routinely use tau imaging to screen subjects and monitor response to therapy.
Takeshi Iwatsubo, M.D., Professor of Neuropathology at the University of Tokyo, said the need for progress against Alzheimer’s is particularly urgent in Japan. Japan is a “super-aging” society that feels the effects of the growing burden of Alzheimer’s before other countries. Dr. Iwatsubo says that while there have been no late stage studies yet to deliver a medicine to clinical care, scientific advancement, aided by biomarkers, has shifted our knowledge of the disease significantly and led to more drugs in development than ever before, targeting individuals in the earliest stages of disease.
In closing…
The Alzheimer’s research community is looking toward a precision medicine treatment model where a combination of drugs will attack multiple pathways in each patient. Biomarkers are a critical part of getting there and the Diagnostics Accelerator, now in its third year, is playing a crucial role. The DxA, which began with a $50 million commitment, has awarded $22 million and funded 28 projects to date, including 22 peripheral biomarker programs and 6 digital programs. This includes six validation studies, which are focused on moving biomarkers that have enough supporting data — blood tests, in particular — toward rapid commercialization